Duration 30:1
NAD+ in Aging: Role of Nicotinamide Riboside and Nicotinamide Mononucleotide
Published 28 Jan 2020
In this episode, Rhonda explains what NAD+ is and why it declines with age. She discusses some of the popular NAD+ boosters like nicotinamide riboside and nicotinamide mononucleotide, what animal and human data says and some concluding thoughts. NAD+ is crucial for our survival. Small amounts of it can be obtained in the diet, but the body recycles it to get most of what it needs. Unfortunately, day to day living plus normal aging can cause NAD+ levels to drop. This causes metabolic and mitochondrial dysfunction, as well as many of the other problems and conditions associated with aging like elevated DNA damage. NAD+ levels can go up when we exercise or fast, but NAD+ precursors like nicotinamide riboside and nicotinamide mononucleotide can also increase NAD+ levels in a dose-dependent manner. However, most of the data on NAD+ boosters comes from animal studies. Whether these boosters are effective – and safe – long-term in humans is still a big question. ▶︎ Get the episode's show notes, timeline, and more https://www.foundmyfitness.com/episodes/nad-nr-nmn Chapters 00:00:00 - Introduction 00:01:01 - Aging 00:02:47 - Overview 00:07:35 - Depletion 00:09:19 - Supplementation 00:11:26 - Animal studies 00:13:47 - Cancer 00:15:57 - Dosage 00:25:44 - Human data 00:28:25 - Storage 00:29:00 - Recap ▶︎ Detailed overview of NAD+ https://www.foundmyfitness.com/topics/nad ▶︎ Detailed overview of nicotinamide riboside https://www.foundmyfitness.com/topics/nicotinamide-riboside ▶︎ Detailed overview of nicotinamide mononucleotide https://www.foundmyfitness.com/topics/nicotinamide-mononucleotide ▶︎ Did you enjoy this podcast? If you want to support me in getting more of this free information out to the public, please consider becoming an FMF premium member! In doing so, you'll also get access to exclusive member benefits, such as a private podcast feed offering early access and occasional bonus episodes, monthly live Q&As with me, a members-only library that includes presentation slides with all of the supporting figures, graphics, references, and quotes. Also included are Rhonda's private notes on topics discussed in the podcast, bi-monthly member-exclusive Science News Digest email, and more. Thank you for your consideration! Learn more here: https://www.foundmyfitness.com/premium ▶︎ Gain valuable insights by running your raw genetic data through the FoundMyFitness report https://www.foundmyfitness.com/genetics/sirtuin
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- Nicotinamide riboside supplementation in humans has been shown to raise NAD+ levels in white blood cells.
- Overview of NAD+
- NAD+ plays an important role in mitigating DNA damage.
- Excessive DNA damage can decrease NAD+ levels by 20-30%.
- Lymphoblastoid cells from centenarians show increased PARP-1 activity.
- Between different species of mammals, higher PARP-1 activity is strongly associated with a longer lifespan.
- Lower organism evidence: A second copy of SIR2, a yeast sirtuin, gave rise to a 30% extension of lifespan.
- NAD+ is required for the activation of sirtuins, which epigenetically regulate a variety of stress response-related processes.
- Energy stress, such as from fasting, exercise, or caloric restriction, increase the NAD+:NADH ratio.
- NAD+ becomes depleted in the brain, heart, and skeletal muscle as we age.
- Decline in NAD+ levels have been associated with many broad categories of clinical disease such as neurodegenerative, cardiovascular, infectious, musculoskeletal.
- NAD+ supplementation has been shown to increase lifespan in models of aging in yeast, worms, and rodents.
- In contrast to de novo synthesis, the predominant source of NAD+ in the body is via the salvage pathway, which is subject to feedback inhibition by nicotinamide.
- Animal studies have shown nicotinamide riboside supplementation is able to increase insulin sensitivity, increase endurance and strength, reverse mitochondrial damage, increase mitochondrial biogenesis, and reverse muscular atrophy.
- Nicotinamide riboside has shown positive effects on the brain in animal, such as increased neurogenesis, decreased cognitive deterioration, decreased amyloid-beta production, and increased synaptic plasticity.
- Nicotinamide mononucleotide has been shown in animals to counter an obesogenic diet, improve markers of metabolic health, improve heart function, and improve cognition and memory.
- A 12-month dietary study of nicotinamide mononucleotide suppressed age-associated body weight gain, enhanced energy metabolism, promoted physical activity, improved insulin sensitivity and plasma lipid profile, and ameliorated eye function and other pathophysiologies in mice.
- NMN has been shown to increase cancer progression in a specialized senescent cell-dependent pancreatic cancer model in mice.
- Plausibility of dosing: comparing animal and human doses.
- Tissue-specific metabolism and bioavailability of NR and NMN.
- Oral administration of NAD produces NR and NMN in the intestine.
- Intravenous administration of NAD, rather than its precursors, shows interesting results: an increase of NAD content and sirtuin expression in the hypothalamic region of the brain.
- Human study #1: 250mg of NR + 50 mg pterostilbene increased blood NAD+ levels by 40%, while a double dose (500 mg NR + 100 mg pterostilbene) increased blood NAD+ levels by 90%. Additionally, there was a decrease in blood pressure, and ALT (a marker for liver health).
- Human study #2: 500mg NR twice daily for six weeks increased NAD+ levels in white blood cells by 60%.
- Concluding thoughts and recap. .. ...Expand 286
firstly for the, pleasant, patient presentation, with amazing revelations of test results of nad, decline with age, using boosters extremely a great masterly study/ & presentation of all pros- cons of all eventualities.
with a final recap!
thanks for this useful educative share! Many regards!
thanks for the clear and concise video!
i saw you in person once but did not want to bother (fashion valley) i would consider you to be one of my heros in t
thank you for what you do
thank you! 4
live long enough to live foreever
thank you for this presentation dr.
cheers. 10
we all need to wait for using supplement at this point till more data available! 2
i was wondering if it makes sense to take a nr/nmn supplement while also ingesting
as you also explain in the video, the nad/nadh ratio in the cell increases when
then such a nad boosting supplement would need to be taken in a fasted state wouldn' t it?
or is the pathway of either nr/nmn supplement somehow separated from the metabolic pathway when a cell is in a fasted state?
they go on to say that as we get older, levels of the nampt enzyme are known to decline and the salvage pathway becomes inefficient at converting nam into nad+. In fact this is known to be one of the main reasons that cellular nad+ declines as we get older. This means that if we want to make sure that nam doesnt build up in the cell, then we must make sure that nampt and the salvage pathway are working optimally, like they were in young cells. Rather than simply trying to fix falling nad+ levels by putting more raw material into the cell (using precursors) the product is designed to fix the underlying reasons why nad+ is actually declining, namely the failing salvage pathway.
i am however concerned of the effect of nicotinamide on sirt2, they claim however that nicotinamide does not effect sirtuins if it doesnt hang around for a long time when the salvage pathway is working properly. I just wondered what your thoughts are on this. Again many thanks for your very detailed video
my mind is foggy most of the time and the nmn has not done anything for that, but i certainly feel the difference in energy levels, it' s really amazing.
i also found that after a few days i had to stop the nmn for a couple of days as it seemed to be making me feel more groggy, so i now take it 2 days on, 2 days off.
the brand i' m using is an american brand called revgenetics, and it' s called advanced nmn, in capsule form. I know it' s also available in powder form too. It' s quite expensive even in capsule form and would cost the earth to take it regularly at the doseages recommended in this video, but i can assure anyone that the effects at the doseage i am on are truly amazing
-thank you, rogan again soon? 17
have you considered an update on your analysis of nad boosters?
enjoyed your take on them and certainly interested in your opinion! 2