NAD+ new findings: Sublingual intake raised NAD+ levels by 76%, firm claims

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Entity Health's new product contains 100mg of NAD+ per sublingual wafer, which is double the dosage of the previous version launched as SL-NAD+ back in 2021. © iX Biopharma

Sublingual administration of nicotinamide adenine dinucleotide (NAD+) significantly increased whole blood NAD+ levels in healthy individuals in a pilot study, with an average increase of 59% after two weeks and 76% after six weeks, a company has claimed.

The pilot study was conducted by NAD Laboratory Ltd, and the test materials were supplied by iX Biopharma. It assessed the efficacy of its second-generation sublingual NAD+ supplement sold under the Entity Health brand.

The filings were revealed in an update to the Singapore Stock Exchange (SGX) where iX Biopharma is listed on the Catalyst Board.

The new product contains 100mg of NAD+ per sublingual wafer, which is double the dosage of the previous version launched as SL-NAD+ back in 2021.

Completed in June this year, results of the pilot study, which have not been peer reviewed, aligned with published data that NAD+ levels decrease with age.

The firm also claims that it showed that the second-generation product has the potential to counteract this decline.

“Instead of taking two wafers to reach that maintenance dose of 100mg, now you can take just one.

“This offers greater effectiveness and convenience. Also, by delivering 100mg in one wafer, we can actually lower production costs and pass those savings on to the consumer,” said Dr Janakan Krishnarajah, chief medical officer at iX Biopharma, the company that owns Entity Health.

Dr Krishnarajah did not reveal the retail price of the new SL-NAD+ but said that it will be launched soon.

Safer and more effective than other delivery formats

Nine healthy individuals were involved in the six-week pilot trial.

Each took two wafers daily, which makes up to 200mg NAD+ per day, for the first two weeks.

In the remaining four weeks, they each took one wafer a day, or 100mg NAD+ daily.  

Venous blood samples were collected at the baseline, week two and week six of the study to determine whole blood NAD+ levels in plasma and within red blood cells.

To assess the safety and tolerability of the treatment, participants responded to questionnaires that captured data on lifestyle factors such as energy levels, mood, sleep, mental clarity, and physical strength.

The results showed that average NAD+ levels rose from 25.6 uM to 40.7 uM at week 2, an average rise of 59%.

By the end of the study, the average NAD+ levels rose to about 45 uM, indicating an average increase of 76% over six weeks.

As for overall wellbeing, all participants reported improvement in at least one area. For example, six out of nine reported an increase in energy levels, and five out of nine reported better mood.

Another significant finding is that despite a lower baseline NAD+ in the older age group of those above 50 years old, both groups reached a NAD+ whole blood level of approximately 45 uM after six weeks of daily supplementation – the average NAD+ level at baseline for those above 50 years old was 24 uM and about 27 uM for those below 50 years old.

“The study aligned with published data showing that NAD+ levels decrease with age, highlighting the potential of SL-NAD+ wafers to counteract this decline,” said the researchers.

Overall, the study concluded that the results indicate effective sublingual delivery for better bioavailability and quicker uptake, said the company.

“The dosing is consistent with no need for conversion to NAD+ compared to NR (nicotinamide riboside) and NMN (nicotinamide mononucleotide) precursor supplements.

“In comparison to NAD+ IV drips, it is more practical, convenient, affordable, and readily available, providing a way for continuous supplementation to maintain constant, optimal NAD+ levels,” said Dr Krishnarajah.

At the moment, the most common health supplements used to raise NAD+ levels are nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR).

These are precursors to NAD+, meaning they will need to be converted into NAD+ in the body.

Dr Krishnarajah also explained how he believes sublingual ingestion offers more advantages than IV drips.

“Intravenous infusions are very invasive. They come with complications like discomfort, and potential risks of bleeding, bruising, and infection.

“Even in a pharmaceutically licensed facility, where everything is pharmaceutical grade, you can't take an infusion every single day. Typically, you might have it once a week, once a fortnight, or more likely once a month.

“To be effective with such infrequent dosing, you need a very high dose each time. This results in super high doses being administered very infrequently,” he said.

He added that people receiving IV injection at high doses often experience symptoms such as abdominal pain, palpitations, and flushing.

“Those who have had these infusions often experience symptoms such as abdominal pain, palpitations, and flushing. You get a big surge of NAD+, and then nothing for the next couple of weeks or a month, followed by another high dose.

“This is not the optimal way to dose NAD+ because it's a molecule consumed constantly by every cell in the body, every second of every minute of every hour of the day. Ideally, you want to deliver it steadily, avoiding the spikes and troughs that come with infrequent high doses.”

The firm is currently conducting studies to compare the efficacy of SL-NAD+ against IV NAD+ and will be sharing the results as soon as the data is available.

Moving forward, the firm will be focusing on improving health span. There are upcoming NAD-based wafer products in the pipeline, which will be unveiled in time to come, said the firm.