Yeast NAD Boosts Cognition, Endurance, Longevity
Over the past few years, some medical researchers have found that the metabolic element called NAD+ – short for Nicotinamide adenine dinucleotide – can seriously increase energy metabolism and longevity. It also results in increased cognition and reduced risk of dementia related diseases such as Alzheimer’s disease.
Wow. What is it and where does it come from you ask?
What is NAD?
NAD is a coenzyme that when oxidized, produces NAD+. When NAD is reduced, NADH is the result.
Yes, the biochemistry involved makes more sense to a chemist. But to simplify, NAD+ has a number of functions within and outside of cells – most notably it acts as an electron transport vehicle for energy production within the cells’ mitochondria.
On top of that, NAD+ activates sirtuins. What are sirtuins? Sirtuins – or SIRT enzymes – switch off genes that promote inflammation and degeneration processes. This means they help inhibit or downplay inflammation and increase cellular longevity.
SIRT enzymes help protect the cell
SIRT enzymes have been linked to increased longevity of each cell along with the whole organism. These associations have been established by scientists over the past decade.
Research has also established that the SIRT1 and SIRT3 enzymes have substantial healthy effects within the body, including:
- increasing insulin sensitivity and thus reducing the risk of diabetes
- increasing artery health and reducing arteriosclerosis
- preventing dementia and brain cell damage
- preventing fatigue and stress
- reducing cancer risk
Much of this research has involved calorie restriction – as this appears to increase SIRT1 availability.
Connection between NAD+ and SIRT
The association between NAD and SIRT enzymes was made years ago, but the ability of their association to reduce the risk of cancer through the protection of DNA – along with better cell metabolism was made in research from the University of Pittsburgh School of Medicine.
In their review of research, they concluded that NAD+’s ability to stimulate energy production along with SIRT’s ability to protect against genetic mutation made NAD+ critical to cancer prevention.
NAD+ and SIRT bind to DNA histones – which link DNA chains – to protect them and regulate them. This results in cell longevity and decreases in cancer risk.
The role of Vitamin B3 and nicotinamide
Along with these findings has come the discovery that a particular nutrient, vitamin B3, supplies the components needed to increase the availability of NAD+ to the cells. That is, in addition to the amino acid L-tryptophan.
But the supplemented forms of vitamin B3 – meaning nicotinic acid or niacin – must be hydolyzed in order to produce nicotinamide – which acts as an effective storage facility for the flush-prone nicotinic acid.
This hydolysis sometimes happens, for example, when a food containing niacin is boiled. And because nicotinic acid is known to produce skin flushing when supplemented in its isolated form, nicotinamide provides an easier nutrient to maintain.
One might be tempted, for example, to directly boost the body’s niacin or even nicotinamide levels. While low-flush nicotinic acid is available, research from Finland’s University of Tampere found that more than 3,000 milligrams of niacin supplementation per day may be too toxic for the liver.
Furthermore, in order to convert to NAD+, nicotinamide must be converted back to nicotinic acid requiring an enzyme called nicotinamidase.
Both niacin and nicotinamide will eventually convert to NAD+ in a three-step enzymatic process, involving the tryptophan amino acid.
The more direct route to NAD+ availability in the cells is Nicotinamide riboside. This has been shown among a number of studies over the past few years.
This research has found that nicotinamide riboside will significantly and immediately boost NAD+ levels, requiring fewer enzymatic steps to complete.
In research from Switzerland’s École Polytechnique Fédérale de Lausanne, scientists found that nicotinamide riboside supplementation significantly increased cellular NAD+ levels in human cell lines and among mice.
They also found that the nicotinamide riboside supplementation significantly increases SIRT1 and SIRT3 availability.
They also found the supplemented mice had significantly more endurance and exercise capacity. The supplemented mice also had higher metabolism and were less prone to gain weight even on a high-fat diet. The supplemented mice also had 48% lower triglyceride levels than the control mice.
Further research by the Swiss researchers found that when Caenorhabditis elegans worms (a parasitic worm) were given nicotinamide riboside, they had 16% longer lifespans.
The most prevalent form of nicotinamide riboside has been found by researchers to be produced in the guts of animals and humans. What is occurring in the gut that boosts the availability of this important nutrient?
Research from Dartmouth Medical School has been investigating the metabolic pathways between niacin and NAD+. Their research has indicated that while niacin can induce NAD+, the precursors to NAD+ are more directly produced in the gut by microorganisms.
In particularly, the researchers have focused upon the probiotic yeast species Saccharomyces cerevisiae – as this yeast species has been found to produce nicotinamide riboside.
Saccharomyces cerevisiae is known primarily for its use as a baking yeast, but is also understood to be a primary probiotic species resident in most healthy guts.
Furthermore, the yeast species Saccharomyces boulardii – also known as brewer’s yeast – another popular resident of healthy guts and used to ferment many foods and beverages – is a subspecies of Saccharomyces cerevisiae.
This means they both produce riboside within the gut, immediately boosting NAD+ levels.
But what about other probiotics?
Yes, the research has clearly shown that while niacin may be found in many foods, nicotinamide is typically produced within the gut by our probiotic bacteria.
Outside of the probiotic yeasts discussed above, research from Italy’s National Research Institute on Food and Nutrition (INRAN) discovered that probiotic supplementation with Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 increased the nicotinamide production among mice compared to control mice.
They also found that the mice given the probiotics had better age-related metabolism than the control mice. The researchers also found that older mice naturally had lower levels of resident probiotics and lower levels of nicotinamide production. They said:
“The results suggest that L. acidophilus and B. lactis may prevent or reduce age-related metabolic dysfunction.”
Research from Sweden’s Lund University found the L. reuteri elevated the availability of succinic acid – which works with NAD within the citric acid (energy production) within the mitochondria.
Sustainable NAD+ availability
The question this leaves us with is how to sustainably boost our NAD+ levels. One might be tempted to simply buy a commercially available supplement in the form of nicotinamide riboside.
Yes, this supplement nicotinamide riboside will most likely have been produced by Saccharomyces cerevisiae yeast in a production facility.
And yes, this would make the nicotinamide riboside a natural form of the nutrient.
The question – also posted by the Dartmouth researchers – was whether the byproducts of NAD+ – which happen to include nicotinamide within the cell – would be properly released from the cell without toxicity.
This is of primary interest because nicotinamide alone will inhibit SIRT enzymes. Not so good for metabolism.
The question becomes: If we flood our bodies with supplemented nicotinamide riboside – to boost metabolism and decrease cellular aging – will there be a backlash?
Twilight Zone supplement?
This reminds me of the old Twilight Zone episode where a water delivery person introduced a housewife to magic water that made her look younger. The backlash was that after the first trial delivery, the price of the next magic water was exorbitant – tens of thousands of dollars.
Worse, if the housewife didn’t continue to drink the magic water, she would age even faster than before she started the program.
Whether nicotinamide riboside supplementation will result in this type of predicament is unknown at the moment.
Furthermore, research on mice and worms may or may not be applicable for humans. At large is the long-term effect of this supplementation and if there are any side effects.
But what is known is that probiotics have been safely living with humans for millions of years, and they cooperatively make and provide many nutrients necessary for our body’s survival.
Perhaps the logical choice is to include a wealth of probiotic foods in the diet, inclusive of foods made with Saccharomyces cerevisiae and Saccharomyces boulardii.
Another strategy – one supported for decades by traditional healers such as Paavo Airola – is the inclusion of supplemented brewer’s yeast into the diet. Brewer’s yeast is a good source for a host of B vitamins, and while Saccharomyces cerevisiae in brewer’s yeast is typically deactivated (heat-killed), the availability of nicotinamide riboside produced by the yeast will be present in the brewer’s yeast.
This reality was confirmed in a 1991 study by researchers from the University of Tasmania as they found brewer’s yeast not only contained nicotinamide riboside, but also improved cholesterol levels among mice.
Fouquerel E, Sobol RW. ARTD1 (PARP1) activation and NAD(+) in DNA repair and cell death. DNA Repair (Amst). 2014 Oct 2. pii: S1568-7864(14)00235-3. doi: 10.1016/j.dnarep.2014.09.004.
Cantó C, Houtkooper RH, Pirinen E, Youn DY, Oosterveer MH, Cen Y, Fernandez-Marcos PJ, Yamamoto H, Andreux PA, Cettour-Rose P, Gademann K, Rinsch C, Schoonjans K, Sauve AA, Auwerx J. The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab. 2012 Jun 6;15(6):838-47. doi: 10.1016/j.cmet.2012.04.022.
Mouchiroud L, Houtkooper RH, Moullan N, Katsyuba E, Ryu D, Cantó C, Mottis A, Jo YS, Viswanathan M, Schoonjans K, Guarente L, Auwerx J. The NAD(+)/Sirtuin Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signaling. Cell. 2013 Jul 18;154(2):430-41. doi: 10.1016/j.cell.2013.06.016.
Marsalková S, Cízek M, Vasil’ M, Bomba A, Nad’ P, Datelinka I, Jonecová Z, Rimková S, Kalinácová V, Styriak I, Bugarský A, Gréserová G. Testing two Lactobacillus plantarum and Lactobacillus acidophilus strains for their suitability as a lipoid probiotic. Berl Munch Tierarztl Wochenschr. 2004 Mar-Apr;117(3-4):145-7.
Van der Meulen R, Adriany T, Verbrugghe K, De Vuyst L. Kinetic analysis of bifidobacterial metabolism reveals a minor role for succinic acid in the regeneration of NAD+ through its growth-associated production. Appl Environ Microbiol. 2006 Aug;72(8):5204-10.
van Niel EW, Larsson CU, Lohmeier-Vogel EM, Rådström P. The potential of biodetoxification activity as a probiotic property of Lactobacillus reuteri. Int J Food Microbiol. 2012 Jan 16;152(3):206-10. doi: 10.1016/j.ijfoodmicro.2011.10.007.
Brasili E, Mengheri E, Tomassini A, Capuani G, Roselli M, Finamore A, Sciubba F, Marini F, Miccheli A. Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 induce different age-related metabolic profiles revealed by 1H-NMR spectroscopy in urine and feces of mice. J Nutr. 2013 Oct;143(10):1549-57. doi: 10.3945/jn.113.177105.
Belenky P, Stebbins R, Bogan KL, Evans CR, Brenner C. Nrt1 and Tna1-independent export of NAD+ precursor vitamins promotes NAD+ homeostasis and allows engineering of vitamin production. PLoS One. 2011 May 11;6(5):e19710. doi: 10.1371/journal.pone.0019710.
Knip M, Douek IF, Moore WP, Gillmor HA, McLean AE, Bingley PJ, Gale EA; European Nicotinamide Diabetes Intervention Trial Group. Safety of high-dose nicotinamide: a review. Diabetologia. 2000 Nov;43(11):1337-45.
Holdsworth ES, Kaufman DV, Neville E. A fraction derived from brewer’s yeast inhibits cholesterol synthesis by rat liver preparations in vitro. Br J Nutr. 1991 Mar;65(2):285-99.