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Is Basis by Elysium Health a Hoax?

The main ingredient in Elysium Health’s Basis is Nicotinamide Riboside (NR)

Elysium Health is only one of several companies selling Nicotinamide Riboside. Their main selling point is the 6 Nobel Prize winning scientists they have signed up as advisors to their company. That is certainly very impressive and lends great credibility to the company.

However, these scientists have had no significant role in researching or creating the Nicotinamide Riboside or the Pterostilbene they combine with it to form their Basis product.

WHY BASIS – IS IT BETTER THAN OTHER BRANDS?

You won’t find any mention of Niagen in the sales and marketing literature about Basis.

Elysium would like you to think that Basis is some exclusive formula created by their founders.

In fact, until recently, they purchased Nicotinamide Riboside AND Pterostilbene from Chromadex like several other brands.

In mid 2017, a nasty lawsuit between Chromadex and Elysium Health resulted in a new formulation for Basis that uses Nicotinamide Riboside they manufacture themselves.

Conclusion: There is no reason to believe Basis is any more effective than any other Nicotinamide Riboside.

NMN and nad+ supplements have advantages

Chromadex and Elysium Health are fighting over the patents for use of Nicotinamide Riboside with hopes to reap the windfalls that come with controlling the market.

However, the research that shows the most dramatic results in health from restoring NAD+ levels was actually accomplished by feeding mice Nicotinamide Mononucleotide (r,r,r).

There have also been many studies showing benefits from using NAD+ injections in mice (r), but the obvious difficulty of using injections in humans has limited the interest.

Both NAD+ and NMN have significant advantages over NR for restoring NAD+ levels throughout the body that we cover below.

Poor Bioavailability from Capsules

NAD+ not effective in drinking water or in capsule form
The NAD+ molecule is twice as large as NR or NMN, and is totally degraded in the Gastro-Intestinal tract, so researchers do not use NAD+ in drinking water of mice and it is not sold in capsule form for humans.

NAD+ in IV or IP injections
Research has been successful using NAD+ injections in mice.

In humans, clinics that provide NAD+ by IV are exploding in popularity, even though they charge over $1,000 a day and require the patient to be hooked up to a drip IV for 8 hours.

NMN and NR poor bioavailability in capsules
NMN and NR capsules are only partially digested in the stomach, but are almost totally metabolized in the liver and excreted as NAM (Liu, 2018).

Sublingual delivery solves the bioavailability problem

Molecules like NMN, NR and NAD+ that have low molecular weight and are hydrophilic can be absorbed through the capillaries under the tongue directly into the bloodstream. This is called Sublingual (under the tongue) delivery.

Sublingual delivery can bypass the stomach and liver.

This solves the bioavailability problem of capsules that get digested in the stomach, so NAD+ can be used instead of NAD+ precursors. It also greatly improves the effectiveness of NMN.

More about Sublingual

THE PROBLEM with CAPSULES – DIGESTED TO NAM

This research published in 2018 confirms that most oral supplements of NMN and NR are digested to NAM in the GI tract or the liver.

At 50Mg/Kg of body weight,  NO NR or NMN made it out of the liver intact.

Future pharmacological and nutraceutical efforts to boost NAD will need to take into account the minimal oral bioavailability of NR and NMN (R)

Unlike in cell culture where NR and NMN are readily incorporated into NAD, oral administration fails to deliver NR or NMN to tissues (R)

Interestingly, we found that neither compound was able to enter the circulation intact in substantial quantities when delivered orally (R)

There is a lot of research and debate about which molecules most easily enter different types of cells.

That question is totally irrelevant if a molecule NEVER REACHES THE BLOODSTREAM.

This study used a small dose – 50 Mg/Kg of bodyweight (equivalent to 250 Mg for a 70 kg human), vs the 300-400 Mg/Kg commonly tested in other research. Perhaps higher dosages allow NAD+ precursors to make it past the Liver to other tissues.

It is clear that for Oral Supplements (Capsules), the bioavailability of any NAD+ precursor is very poor outside of the Liver.

SUBLINGUAL DELIVERY BYPASSES THE STOMACH AND LIVER

Sublingual (under the tongue) delivery can provide rapid absorption via the blood vessels under the tongue rather than via the digestive tract. (r,r,r)

The absorption of the different molecules delivered through the sublingual route can be 3 to 10 times greater than oral route and is only surpassed by direct IV injection (r).

SUBLINGUAL CAN BE MORE BIOAVAILABLE THAN IP INJECTION !

With intraperitoneal injection, the primary route of absorption is via the mesenteric vessels, which drain into the portal vein and pass through the liver before reaching the bloodstream.

This means, IP avoids the GI tract, but is still sent directly to the Liver, where much of it is converted to NAD+. Elevated NAD+ in the liver is good, but its far better to reach the bloodstream with intact NMN.

Sublingual delivery is not filtered by the Liver and can reach systemic circulation intact, so can actually result in greater bioavailability that direct injection! Some examples are:

  • A sublingual formulation of zol… exhibited a faster rate of absorption and higher drug exposure as compared to subcutaneous injection (r)
  • sublingually administered epin… results in more rapid absorption and a higher peak plasma concentration compared to injected epin… .(r)
  • 40mg of sublingually administered pir.. was found to be as effective as a 75 mg intramuscular injection of dicl… (r)

NAD+ METABOLISM IN HUMANS

NAD+ can be synthesized in humans from several different molecules (precursors), thru  the De Novo  and Salvage Pathways.

The salvage pathway sustains 85% or more of our NAD+ (14), with approximately 3g of NAM metabolized to NMN and then to NAD 2-4 times per day (14).

Nampt is the rate-limiting step in the salvage process (97).

As we age, Nampt enzyme activity is lower, resulting in less NAM recycling, less NAD+, more disease and aging (97,101).

SUBLINGUAL NMN AND NAD+ BYPASSES THE NAMPT BOTTLENECK

Restoring NAD+ in the Liver does not solve NAD+ deficiency throughout the body.

In the Liver, the CD38 enzyme metabolizes NAD+ to NAM, which is excreted to the rest of the body (r).

Sublingual delivery of NMN or NAD+ directly to the bloodstream bypasses the liver and the Nampt bottleneck that is the root cause of NAD+ deficiency in many tissues.

Why no sublingual NR?

NR is not stable by itself (see below) , so Chromadex and Elysium Health both add Chloride to make it stable.
ALL NR sold is actually Nicotinamide Riboside CHLORIDE
Unfortunately, the taste is not acceptable for sublingual use.

So NR is only available in capsule form, which much pass through the stomach and liver where it is metabolized to the less effective Nicotinamide (Liu, 2018) .

NAD+ SUPPLEMENTATION

Restores NAD+ in brain, Increases Metabolism

Once in the bloodstream NAD+ was thought to be too large to cross the cell membrane, making it ineffective at restoring the NAD+ contents inside the cells of many tissues. In this article we show that is not true for heart and brain, and perhaps other tissues.

In fact, this research published in March 2018 shows NAD+ is able to cross the blood brain barrier and quickly increases levels of NAD+ in the hypothalamus, while NR and NMN do not.

Administration of 1 mg/kg of NAD+ reduced hunger and weight gain, and increases energy expenditure and fat burning in mice (r).

Elevating NAD+ levels the hypothalamus has great impact throughout the body, as it regulates hunger and energy expenditure.

Restoring NAD+ levels in the hypothalamus to those of a young animal is very likely to have a positive impact on organs and tissues throughout the body.

(more about the importance of hypothalamus as master regulator of metabolism below)

Even more tantalizing are the possible implications for aging itself.
That the hypothalamus as master aging clock, is a credible theory on aging.

Not limited by homeostasis

Supplying NAD+ direct to the bloodstream bypasses the liver, temporarily enabling a greater increase in NAD+ levels.

Any NAD+ (or NMN) in the bloodstream will get filtered out by the liver in 30-60 minutes.

So after an initial spike in NAD+, the same limits imposed by homeostasis in the liver will likely take effect.

This is why NAD+ clinics use slow IV drips to constantly supply NAD+ to the bloodstream rather than a single large daily injection of NAD+.

Frequent dosages throughout the day of our NAD+ sublingual tablets provide a steady supply of NAD+ direct to the bloodstream, avoiding the limits imposed by homeostasis in the liver.

NMN SUPPLEMENTATION

Blood Vessel Re-growth, Strength, Endurance

NMN shows a particular ability to restore vascular growth and benefit tissues such as muscle and heart that haven’t been replicated in studies with NR or NAD+.

Below are the three studies that made the biggest splash’s about the potential for reversing aging by restoring NAD+ to youthful levels that have ALL been accomplished using NMN

After 6 days of NMN, 22 month old mice  had the muscle capacity, endurance and metabolism of 6 month old  mice (2013 Sinclair study)

NMN effectively mitigates age-associated physiological decline in mice (2016 Mills Long Term study)

“The old mice became as fit and strong as young mice” (Sinclair, 2018)

The third study identifies the key cellular mechanisms behind vascular aging and the critical role it plays on muscle health.

Dr Sinclairs team fed NMN to old mice. After two months, the mice had increased muscular blood flow, enhanced physical performance and endurance and the old mice became as fit and strong as young mice.

NEW BLOOD VESSELS sprouted within the skeletal muscles, capillary density increased and matched the capillary growth of young mice.

  • NMN restored the vascular system of old mice to that of young mice.
  • Mice treated with NMN had  had nearly 100% increased endurance.

Renewed capillary growth and increased blood flow may help reverse heart and neurological problems in addition to sarcopenia.

According to Dr. Sinclair, the same mechanism could spur the creation of blood vessels in the brain, where “the lack of oxygen and buildup of waste products sets off a downward spiral of disease and disability,” such as Parkinson’s and Alzheimer’s.

NMN is stable in the bloodstream

Sublingual NMN does bypass the liver to send the NMN direct to the bloodstream where it can be used by cells that have their own salvage pathway to increase intercellular NAD+.

In vivo, NMN is found in blood plasma. When added to blood in vitro, it is stable. (Canto,Brenner 2016)

Our results further demonstrate that while NR is spontaneously converted to NAM in cell-free plasma, NMN is more resistant to this process.

On the contrary, NMN is stable in plasma and there is no NAM increase in NMN samples up to 1 h incubation.

 

homeostasis uncertain

500% NAD+ increase with NMN ?
The chart at right shows NAD+ increase measured in the liver (and soleus muscle) after 60 days of supplementation with NMN (Sinclair, 2018).

This is the best indication we have to date, but was with mice. With humans, there has been a Japanese clinical study completed, and one by Dr Sinclair, but neither has yet published the results.

We doubt they will show anywhere near this 500% increase, as NMN and NR are so closely related. But this does provide some hope that NMN is not subject to the same limits on the long-term increase of NAD+ levels as have been found with NR (above).

Alzheimers

Alzheimer’s disease (AD) pathogenesis is widely believed to be driven by the production and deposition of the β-amyloid peptide (Aβ). Evidence now indicates that the solubility of Aβ, and the quantity of Aβ in different pools is related to disease state (r).Researchers believe that flaws in the processes governing production, accumulation or disposal of beta-amyloid are the primary cause of Alzheimer’s (r).

In studies published in 2017 and 2018 NMN decreased β-amyloid buildup, while NR did not.

“NR lessened pTau pathology in both 3xTgAD and 3xTgAD/Polβ+/− mice but had no impact on amyloid β peptide (Aβ) accumulation”(Hou, 2018)

“NMN decreased β-amyloid production, amyloid plaque burden, synaptic loss, and inflammatory responses in AD-Tg mice” (Yao, 2017)

Heart Disease

2 separate studies to treat a form of heart disease called Friedreich’s Ataxia with NR and NMN were published in 2017. Treatment with NMN was successful, while NR did not improve cardiac function.

“Remarkably, NMN administered to FXN-KO mice restores cardiac function to near-normal levels. “(Martin, 2017)

“In conclusion, NAD+ supplementation with NR in the FRDA model of mitochondrial heart disease does not alter SIRT3 activity or improve cardiac function.”(Stram, 2017)

Misc

NMN was able to mitigate most age-associated physiological declines in mice Treatment of old mice with NMN reversed all of these biochemical aspects of aging

Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice (mills, 2016)

Raising NAD+ levels in old mice restores mitochondrial function to that of a young mouse

Restore the mitochondrial homeostasis and key biochemical markers of muscle health in a 22-month-old mouse to levels similar to a 6-month-old mouse

Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging (Gomes, Sinclair,2013)

DNA Repair

This study showed supplementation with NMN was able to repair the DNA in cells damaged by radiation

The cells of old mice were indistinguishable from young mice after just one week of treatment.

A conserved NAD+ binding pocket that regulates protein-protein interactions during aging (Sinclair, 2017)

WEIGHT

NMN was immediately utilized and converted to NAD+ within 15 min, resulting in significant increases in NAD+ levels over 60 min

Administering NMN, a key NAD+ intermediate, can be an effective intervention to treat the pathophysiology of diet- and age-induced T2D

Surprisingly, just one dose of NMN normalized impaired glucose tolerance

Nicotinamide Mononucleotide, a Key NAD+ Intermediate, Treats the Pathophysiology of Diet- and Age-Induced Diabetes in Mice (Yoshino, 2011)

NAD(+) levels were increased significantly both in muscle and liver by NMN

NMN-supplementation can induce similar reversal of the glucose intolerance

NMN intervention is likely to be increased catabolism of fats NMN-supplementation does mimic exercise

Head to Head Comparison of Short-Term Treatment with the NAD(+) Precursor Nicotinamide Mononucleotide (NMN) and 6 Weeks of Exercise in Obese Female Mice (Uddin, 2016)

NMN significantly increased the level of NAD+ in the heart

NMN protected the heart from I/R injury

Nicotinamide mononucleotide, an intermediate of NAD+ synthesis, protects the heart from ischemia and repercussion (Yamamoto, 2014)

NMN reduces vascular oxidative stress

NMN treatment normalizes aortic stiffness in old mice

NMN represents a novel strategy for combating arterial aging

Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice (de Picciotto, 2016)

NMN can reduce myocardial inflammation NMN thus can cut off the initial inflammatory signal, leading to reduced myocardial inflammation

Short-term administration of Nicotinamide Mononucleotide preserves cardiac mitochondrial homeostasis and prevents heart failure (Zhang, 2017)

ENERGY

Remarkably, NMN administered to FXN-KO mice restores cardiac function to near-normal levels.

Restoration of cardiac function and energy metabolism upon NMN supplementation

Remarkable decrease in whole-body EE and cardiac energy wasting

Nicotinamide mononucleotide requires SIRT3 to improve cardiac function and bioenergetics in a Friedreich’s ataxia cardiomyopathy model

VISION

Exogenous NMN prevents photoreceptor degeneration and restores vision

NMN rescues retinal dysfunction in light-induced degeneration

 

NAMPT-mediated NAD+ biosynthesis is essential for vision in mice (lin, 2016)

Clinical Studies

Completed and pending publication

Beginning 2018

  • 2018 Sinclair Metrobio study – Phase 2

The Phase 1 study by Dr Sinclair has been completed, and they are ready to go forward with the Phase 2 study, so we can conclude there were positive results, and no negative side effects, else they would have to publish those immediately.

In the University of Washington study, participants are 50 healthy women between 55 and 70 years of age with slightly high blood glucose,BMI and triglyceride levels.

Using a dose of 2 capsules of 125mg NMN per day over a period of 8 weeks, researchers are testing for:

  • change in beta-cell function
  • works to control blood sugar
  • blood vessels dilate
  • effects of NMN on blood lipids
  • effects of NMN on body fat
  • markers of cardiovascular and metabolic health

The active supplementation portion of this study has ended, but testing of metabolic parameters will continue for 2 years after supplementation has ended.  So researchers know the immediate effects and  preliminary results are expected to be announced in 2018, with  final results expected in 2020.
 

NR SUPPLEMENTATION

NR is NOT STABLE and not found in blood plasma

In both mice and humans, studies repeatedly failed to find any NR in the blood plasma at any time, even after very high dosages of NR (97, 98, 99) NR has been found at trace levels in inside blood cells.

The following quote from this Dr Brenner study also did not find NR in bloodstream after oral supplements, but was found in trace amounts after Injection.

NR varied and displayed no response to NR administration… but was detected after IP of double labeled NR.

When added to blood plasma in the lab, NR is unstable and quickly deteriorates to NAM (Canto,Brenner 2016).

∼10% of NR degraded after 10 min and ∼66% degraded after 1 h (Fig. 8e), which is further illustrated by gradual increase in NAM abundance in the samples (Fig. 8g).

NR is quickly taken up by cells and elevates NAD+ in the liver, but is not found outside the liver in blood plasma. This implies much of the overlapping benefits of NR with NMN and NAD+ are due to the increased NAD+ created in the liver.

NR effective in liver short term

The Trammell research shows that in the liver, NMN and NAD+ must be degraded to NR before crossing the cell membrane before converting back to NMN and then NAD+. This may be why a single dose of NR increases NAD+ levels in the liver more than NMN, NAM, NA and other NAD+ metabolites as shown here.

This short term advantage for NR in the liver does not apply to all tissues, as both NMN and NAD+ have been shown to cross the cellular membrane in heart, brain, and other tissues.

NR limited by HOMEOSTASIS


The Liver is the “engine” that supplies the great majority of NAD+ to the rest of the body (Liu,2018).

In the Trammel thesis, Dr Brenner consumed 1000 mg of NR. At day 1, his NAD+ was increased by 270%.

The Elysium study used 500 mg of NR per day (plus pterostilbene). NAD+ was increased in blood plasma by 90% at 30 days, and dropped to 55% at 60 days.

The authors of the Elysium study believe that homeostasis limits the maximum increase in NAD+ that can be sustained over the long term.

High levels of NAD+ can induce homeostatic mechanisms to restrain further increases.

This may explain why those taking NR capsules often report increased energy, which seems to fade after some time. Homeostasis has brought their NAD+ levels back down and the hypothalamus isn’t getting the message to increase metabolism as it did back on day 1.

While 50% increase is helpful, keep in mind that as we age, our NAD+ levels drop in half. So the average person would need to DOUBLE their NAD+ levels – a 100% increase – to reach the levels they have in youth.

SUMMARY:

    • Sublingual delivery is required for all NAD+ metabolites and precursors to avoid digestion in the stomach and liver.
    • NAD+ clinics use slow drip IV of NAD+ to avoid the stomach and liver. They are exploding in popularity, but the extreme cost and time required for treatment severely limit their application for the general public.
    • Sublingual NAD+ delivery solves the bioavailability problem and mimics the slow drip delivery used successfully by NAD+ IV clinics.
    • Sublingual NAD+ is not subject to the homeostasis that limits NAD+ increase with NR (and perhaps NMN), as it is supplied directly to the bloodstream.
    • We believe the ability of NAD+ to increase metabolism through the hypothalamus has a great impact on the entire body. This is accomplished directly from increased NAD+ circulating in blood plasma, and not from NMN or NR.
    • Other organs such as heart, liver, kidney, and lungs also clearly benefit from increased circulating NAD+, but there is evidence NR an NMN may have similar effectiveness.
    • Exogenous NR increases circulating NAD+ levels, but after several weeks, that increase is severely limited by homeostasis.
    • Exogenous NMN elevates NAD+ levels similar to NR, but seems to be less limited by homeostasis. Publication of recently completed research should shed more light on that question.


NMN demonstrates a remarkable ability to rapidly restore vascular growth that has not been shown with use of NR or NAD+.

 

Sublingual NAD+ will lead to a greater increase in circulating NAD+ than NR or NMN supplements.