Nicotinamide Riboside supplements aid metabolic health in Mice

cells artResearchers at the Wageningen University in the Netherlands took a different approach to understand the effect of NAD+ pre-cursers and their influence on health. They presented a poster publication during the “10th World Congress on Polyphenols Applications” about an experiment  to test the effects of marginal dietary supplementation with Nicotinamide Riboside (NR) on metabolic flexibility and anti-oxidant response in mice exposed to a high fat diet. This is in particular interesting because most studies with NR have been done at higher therapeutic levels as opposed to levels more typical for daily supplementation with an aim to maintain health.

The researchers fed two groups of adult male mice with a high fat diet containing dosing of 5 or 30 mg NR/kg. They measured body weight, lean mass, fat mass and feed intake weekly. After 14 weeks the metabolic flexibility was assessed with a fasting and re-feeding challenge using indirect calorimetry. With indirect calorimetry a measurement of respiratory exchanges takes place. Oxidation of the energetic substrates by the body is associated with oxygen consumption, carbon dioxide production, and heat release specific to the nature of the energetic substrates being oxidized. In the following week (so at 15 weeks) the researchers determined the anti-oxidant response in epididymal white adipose tissue.

The results showed that in the fasting and re-feeding challenge, the delta respiratory exchange ratio (ΔRER) was higher when comparing 30 to 5 mg/kg NR dosing thus indicating an increase in metabolic flexibility. In addition the expression levels of anti-oxidant genes were enhanced in the 30 mg/kg group compared to the 5 mg/kg group. The body physiological parameters were not affected by the dietary NR.

nr nad namFrom these results it is still not possible to conclude what is the minimum level at which NR supplementation impacts the body as there are no intermediate dose test results between 5mg and 30mg / kg but it seems reasonable to conclude that NR supplementation does impact at a dosing level of  30mg / kg in mice.

Using FDA specified guidelines  we can calculate the Human Equivalent Dose (HED) for the NR diet given to the mice. Using this guideline 30mg/kg dosing in mice translates into a HED of approx. 2.4mg/kg. Or into approximately 170mg daily nicotinamide riboside dosing for a person weighing 70kg.  This is below the limit wrt to side effects and safety and less than the typical serving sizes of 250mg of supplements on the market. The result supports the view that NR supplementation may help maintain health as we age.

Here the updated overview of Nicotinamide Riboside dosing in various studies.

You can find the poster presentation summary here.

Is Basis by Elysium Health a Hoax?

As we age, levels of the co-enzyme Nicotinamide Adenine Dinucleotide NAD+ drop significantly in multiple organs, which disrupts our bodies ability to fight inflammation, disease, and physiological decline  (5,8,10).

NAD+ decrease is described as a trigger in age-associated decline(23), and perhaps even the key factor in why we age (5).

In 2013, Research published by Dr Sinclair  of Harvard stunned researchers by showing that short term supplementation with Nicotinamide MonoNucleotide (NMN)  reversed many aspects of aging, making the cells of old mice resemble those of much younger mice, and greatly improving their health.

Since then, dozens of other studies have been published investigating the efficacy of supplementation with NAD+ precursors such as NMN and Nicotinamide Riboside (NR) in treatment and prevention of a wide range of disease including cancer, cardiovascular disease, diabetes, Alzheimers, Parkinsons, and more (5,6,7,9,10,11,13,14,15,16,23).

BASIS USES NICOTINAMIDE RIBOSIDE

NR and NMN are precursors that are used by our bodies to replenish NAD+ levels.

In 2004 Dr Charles Brenner published a paper showing that the enzyme Nrk1 can catalyze NR directly to NMN (100) which might make it a much more effective precursor to NAD+.  Although NR is unstable by itself, Dartmouth University has patented production methods that combine it with Chloride which makes it stable.

Chromadex has licensed this technology and has been selling NR commercially since 2014 under the brand name “Niagen”.

Basis is the brand name used by Elysium Health to market their Nicotinamide Riboside product.

WHAT IS NAD+

NR benefits chartNAD+ is a key co-enzyme that the mitochondria in every cell of our bodies depend on to fuel all basic functions. (3,4)

NAD+ play a key role in communicating between our cells nucleus and the Mitochondria that power all activity in our cells (5,6,7)

NAD+ LEVELS DECREASE WITH AGE

NAD+ levels decreaseAs we age, our bodies produce less NAD+ and the communication between the Mitochondria and cell nucleus is impaired. (5,8,10).

Over time,  decreasing NAD+ impairs the cell’s ability to make energy, which leads to aging and disease (8, 5) and perhaps even the key factor in why we age (5).

NAD+ METABOLISM IN HUMANS

NAD+ is synthesized in humans by several different molecules (precursors), thru 2 different pathways:
De Novo Pathway

  • Tryptophan
  • Nicotinic Acid (NA)

Salvage Pathway

  • NAM – Nicotinamide
  • NR – Nicotinamide Riboside
  • NMN – Nicotinamide MonoNucleotide

The NAD+ supply is not stagnant – it is constantly being consumed and replenished, with the entire NAD+ pool being turned over 2-4 times per day (14).

This recycling is through the salvage pathway, where the enzyme Nampt catalyzes NAM to NMN, which is then metabolized to NAD+.


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

Many studies have confirmed the importance of Nampt in maintaining sufficient NAD+ levels, such as the quote below from a 2016 study that used mice lacking Nampt in muscle fiber:

“NAD content of muscle was decreased by ~85% confirmed the prevailing view that the salvage route of NAD synthesis from NAM sustains the vast majority of the NAD” (97)

These mice exhibited normal muscle strength and endurance while young, but deteriorated rapidly as they aged which confirmed Nampt is critical to maintaining NAD+ levels.

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

NMN and NR SUPPLEMENTS CAN BYPASS NAMPT

NR had been known for decades, but was not thought to be that important until 2004 when Dr. Charles Brenner discovered the enzyme NRK1 can phosphorylate NR directly to NMN, bypassing the Nampt “bottleneck” (100).

This newly discovered “shortcut” in the NAD+ salvage pathway found that NR can be metabolized directly to NMN to boost NAD+ levels more effectively than NAM.

MOST NR IS FIRST METABOLIZED TO NAM

When taken orally as a supplement, most NR does not make it through the digestive system intact, but is broken down to NAM (97,98,99).

Even when taken at very high dosages, NR has not been detected in the bloodstream in any research (97,98,99).

“This evidence indicates that NR is converted to NAM before absorption occurs and that this reaction is the rate-limiting step ” (98)

“NR has been shown be converted to Nam before being absorbed or reaching tissues” (99)

“we were surprised to find that NR exerts only a subtle influence on the steady state concentration of NAD in muscles. Our tracer studies suggest that this is largely attributable to breakdown of orally delivered NR into NAM prior to reaching the muscle. ” (97)

Note:NAM does elevate NAD+, but is on the “wrong” side of the Nampt bottleneck, which limits it’s effectiveness

WHAT WE RECOMMEND

[post-content id=59982]

NOBEL PRIZE WINNING ADVISORS

1000s of articles have teased us with the possibility that taking Niagen could halt or maybe even actually reverse some of the signs of aging. Of course there is a lot of skepticism with such claims.

Chromadex has been producing the only commercially available form of Niagen and supplies it to 20 or more different companies that put their own brand name on the bottle and sell to customers.

Elysium Health is only one of these sellers, although they have fairly deep pockets and extensive connections among top researchers in the field.

They have also enlisted 6 Nobel Laurete scientists to serve as advisors to the company, which lends a great deal of credibility.

However, these scientists have had no significant role in researching,creating or testing Basis or either of the ingredients used.

screen-shot-2016-12-01-at-2-21-53-pm

Elysium Health makes a change to the formula for Basis


Basis contracted to buy Nicotinamide Riboside Chloride (often referred to as NR, or the brand name Niagen), and combine it with another off the shelf product from Chromadex, Pterostilbene.

But in June 2016, Elysium got into a contract dispute with Chromadex and later sued Chromadex for abusing the patent process.

Their goal seems to be to invalidate Chromadex patent(s) so they could produce their own version, which appears to be what they are doing now.

Elysium has changed the product information on their website to list “Nicotinamide Riboside”, without the Chloride.  A key patent Chromadex has licensed the rights to involves adding the Chloride to make it more stable.

This new ingredient used by Basis likely has the same effects in the human body, but we don’t really know for sure.

It seems Elysium Health plans to go forward with this revised formula for now, and continue to use previous test results obtained with their prior  formula that used Chromadex Nicotinamide Riboside Chloride.  It will be interesting to see how that strategy holds up going forward.

Elysium Health has some very slick Marketing people

So now they have changed their product to use a slightly different ingredient, but want to smooth it over and not cause customers to worry about it.

Their answer is to portray the change as something they did on purpose – to MAKE THE PRODUCT BETTER.

When a customer questioned the change, this is how they answered on their Facebook page:

Hi Anne–

Thank you for reaching out to us with your questions. I’d be happy to provide additional information for you here!

From the start, Elysium has always been committed to bringing superior, high-quality supplements to market. As part of that effort, we have established a new supply chain, located in the United States, that utilizes a proprietary process to produce Nicotinamide Riboside — the first of its kind for the production of Basis, and this does fully meet the GMP standard as outlined by the FDA. We believe our vertically integrated supply chain benefits our customers as it enables us to better manage manufacturing, packaging, shipment and eventually the expansion of our new product line.
While the specific Basis formulation and the amount of each ingredient have not changed, this new production process has allowed us to take an exceptional product and make it even purer. This reflects our ongoing commitment to being a trusted source for our customers by continually exceeding the highest standards in the industry.

In regard to your question about GMO’s, this does not apply to Basis as we don’t have food products in our ingredients eligible for genetic modification. Basis is produced by nature identical synthesis, meaning that the active molecules are constructed to be nature identical. This process is preferable to attempting to distill down the ingredients from food as the final product is purer than what the bi-product would be via distillation.
If you have other questions or if there is anything we can do to help, my team can be reached directly here or by email at care@elysiumhealth.com or phone at 888-220-6436.

Pretty slick, I thought. No, they didn’t substitute something they just threw together to get around the patent and supply problem – they made something more pure and trustworthy.

I don’t know who is going to with the legal battles between Chromadex and Elysium Health, but I see Elysium as way ahead in the marketing department even if I don’t really trust their honesty.

WHY BASIS – IS IT BETTER THAN OTHER BRANDS?

Why Logo White red You’ll find very little 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, they purchase Niagen from Chromadex like several other brands.

The research and testing that has generated so much excitement has been done with Nicotinamide Riboside from Chromadex.

There has been no research published to show that Pterostibene makes Niagen work any better.

[box]Conclusion: ALL Niagen comes from Chromadex, there is no proof that Basis is any more effective than other brands of Niagen.[/box]

THE COST

dollar sign moneybagBasis is available only thru their website for $60 a bottle, which would last for one month if taking 2 pills per day (250mg of Niagen).

Recent research indicates that the optimum dosage for maximum increase in NAD+ levels is at least 250mg per day, or more.

In fact, the best evidence on recommended dosage will hopefully soon be available from a recently completed study sponsored by Elysium Health themselves.

This study of 120 elderly patients tested blood NAD+ levels of 250mg and 500mg of Elysium Health Basis vs placebo.

Once this study is published we’ll have a lot better idea if one bottle per month is sufficient

IS IT WORTH THE EXTRA COST?

If you know that Basis is Niagen + Pterostilbene, and start searching for “Niagen”, you quickly realize you can get the same thing for 1/2 the cost or less elsewhere.

Screenshot 2016-01-25 15.21.18

[box]Conclusion: Since ALL Niagen comes from Chromadex, there is no difference in the quality among brands[/box]

What does Basis do?

The field of Anti-Aging supplements is littered with scams and hoax products that are supposed to miraculously stop the aging process.

It is for that exact reason that Elysium Health DOES NOT market Basis specifically as an anti-aging pill.

Rather, they focus on some specific areas that their pill may help with such as:

— DNA repair
— Energy production
— Cellular detoxification
— Protein function

Basis – Conclusion

  • Niagen plus Pterostilbene (similar to Resveratrol)
  • Pre-eminent antiaging researcher as cofounder of company
  • 6 Nobel laureate scientists on advisory board
  • By far the most expensive Niagen on the market
  • One bottle a month may not be enough for optimum results

 

WHAT WE RECOMMEND

[post-content id=59982]

References:

[post-content id=55017]

High Fat Diet Lowers Risk for Diabetes

Glass Of Milk Being PouredDespite having been considered harmful in the past, new studies have failed to find a link between saturated animal fat and heart disease.

Additionally, not all saturated fats are created equal, and some of them may even be beneficial. This may be particularly true of dairy fat, which contains fatty acids that can have biological effects.
Today’s study looks at the relationship between high-fat dairy consumption and the risk of type 2 diabetes.

 

Background

In the past decades, dairy fat may have been unfairly demonized.

In fact, the evidence against dairy fat is severely limited, and the majority of the evidence suggests that it has no effect on heart disease risk (12).

Yet, many current dietary guidelines still recommend a limited intake of full-fat dairy.

Dairy fat’s association to type 2 diabetes has been much less studied. Observational studies have provided mixed results, suggesting that dairy fat may have neutral or beneficial effects on type 2 diabetes (345).

Previous observational studies have relied on self-reported intake of dairy fat, which tends to be inaccurate. A better approach is to directly measure circulating markers of dairy fat intake.

Dairy fat contains a few types of rare fatty acids, such as pentadecanoic acidmargaric acid and trans-palmitoleic acid, not found in significant amounts in other foods (678).

Therefore, their blood levels may indicate how much dairy fat a person eats (910).

Article Reviewed

A group of researchers from Harvard and Tufts University examined whether circulating markers of dairy fat intake were associated with type 2 diabetes risk.

Circulating Biomarkers of Dairy Fat and Risk of Incident Diabetes Mellitus Among Men and Women in the United States in Two Large Prospective Cohorts.

Study Design

This prospective observational study examined the association between circulating markers of dairy fat intake and the risk of developing type 2 diabetes.

It included 3,333 adults from two previous observational studies — the Nurses’ Health Study and the Health Professionals Follow-Up Study.

The participants were 30–75 years old, and half of them were overweight or obese. However, none had type 2 diabetes, heart disease or cancer at the start of the study.

The researchers took blood samples and analyzed the amounts and types of circulating fatty acids in the participants’ blood fluid (plasma) and red blood cells.

After an average of 15 years, they were tested for type 2 diabetes by questionnaire.

Finally, the researchers used statistics (pooled multivariate analyses) to examine the association of type 2 diabetes with circulating levels of pentadecanoic, margaric and trans-palmitoleic acids.

Bottom Line: This prospective observational study examined the association between type 2 diabetes and markers of dairy fat intake.

Finding 1: Markers of Dairy Fat Intake Were Linked to a Lower Risk of Diabetes

During the 15 years of follow-up, 277 new cases of type 2 diabetes were diagnosed.

This study showed that individuals with high levels of pentadecanoic, margaric and trans-palmitoleic acids in their blood fluid (plasma) were at a significantly lower risk of developing type 2 diabetes.

Specifically, those in the highest quartile of pentadecanoic acid (PA) levels were at a 44% lower risk of becoming diabetic, compared to those in the lowest quartile.

Similarly, high margaric acid (MA) levels were linked to a 43% lower risk, while trans-palmitoleic acid (TPA) levels were linked to a 52% lower risk.

The findings are presented in the charts below.

Chart One Dairy Fatty Acids

Chart Two Dairy Fatty Acids

These results are supported by several previous observational studies (1112131415).

Similar results were obtained when fatty acid levels in red blood cells were examined, although only margaric acid remained significantly associated with a lower risk of diabetes.

Bottom Line: Circulating markers of dairy fat intake were significantly associated with a lower risk of type 2 diabetes.

Why Might Dairy Fat Reduce the Risk of Diabetes?

The factors responsible for the associations seen in the present study are unknown.

They might be any of the fatty acids examined, other related factors in milk or lifestyle factors associated with high dairy fat consumption.

Scientists have suggested that several milk fat constituents may play a role. These include vitamin D, omega-3 fats, short- and medium-chain fats and gangliosides (16).

In the present study, when all three markers of dairy fat were added to the same statistical model, only trans-palmitoleic acid remained significantly associated with a reduced risk of type 2 diabetes.

The authors speculated that trans-palmitoleic acid might affect type 2 diabetes due to its similarities to palmitoleic acid, which is a fatty acid that may reduce liver fat production and improve insulin sensitivity in muscles (1718).

However, before a solid conclusion can be reached, the individual milk fat components need to be examined in randomized controlled studies.

Bottom Line: Why dairy fat might protect against type 2 diabetes is unclear. The authors suggest that trans-palmitoleic acid may be responsible.

Limitations

The study’s primary limitation was its observational design, which was otherwise excellent.

Additionally, only 71% of the participants were fasting when blood samples were taken. However, this is unlikely to have significantly affected the results.

Summary and Real-Life Application

This study suggests that eating high-fat dairy products, such as cheese, butter and cream, may protect against diabetes.

However, it did have an observational design, meaning that its findings do not provide any hard evidence about causality.

Regardless, dairy fat appears to be a healthy dietary component. The majority of studies suggests that dairy fat is not the villain it was previously made out to be.