Study shows NMN increases in blood flow and endurance in elderly mice

A new mouse study on NMN (another NAD+ precursor nearly the same as NR) that was published today showed blood flow and endurance improved (56% to 80% for endurance) when given to older mice that were excerising but interestingly, not for the sedentary group.


A decline in capillary density and blood flow with age is a major cause of mortality and morbidity. … Treatment of mice with … (NMN) improves blood flow and increases endurance in elderly mice by promoting SIRT1-dependent increases in capillary density, an effect augmented by exercise or increasing the levels of hydrogen sulfide (H2S), a [dietary restriction (DR)] mimetic and regulator of endothelial NAD+ levels. These findings have implications for improving blood flow to organs and tissues, increasing human performance, and reestablishing a virtuous cycle of mobility in the elderly.

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Highlights of a 50 minute interview with NR researcher Charles Brenner

Charles Brenner, a biologist at the U of Iowa, who I heard give a presentation at the end of 2016 was recently interviewed for 50 minutes on the Live Long and Master Aging podcast. Brenner says overeating, lack of sleep, too much sunlight, oxygen and alcohol “deregulate” NAD+. He added that heart failure also deregulates NAD+.

He emphasizes that mice with diabetes, are overweight, have heart failure, neuropothy or neurodegeneration will benefit much more from NR than mice on a good diet and exercise.

Brenner took 1,000 mg of NR for a week as a participant in a human trial of one. I asked in December 2016 if he still takes that amount, and he replied that he lowered it to 250 mg a day. After a while he says his digestion improved but didn’t feel more energy because he already is “a high energy person” at 56. In this interview he added that he “lost 2 inches in his waist “which was great”, and he wasn’t really watching what he eats. Guarente, a co-fonder of Elysium said last year that their 8 week trial didn’t show weight loss so, it might occur but after a longer period.

Brenner thinks there is a positive feedback loop where “if you’re sleeping a little bit better, thinking a little bit clearer and going to the expense of taking a supplement that has a non-trivial price point* “I think there is a positive feedback of taking care of yourself. I exercise a lot, but I did feel that adding NR to my morning routine was improving my digestion , improving my sleep and probably having an effect on my focus as well”.

Brenner said he now is more careful about diet increased the amount of NR to 500 mg sometime in 2017.

Brenner: “There have been trials initiated for diabetes and heart failure, however, we can’t talk about results yet and there are trials whose results will be made public in coming months that say some things about common conditions … studies with people taking medications have not shown interactions with NR. ” The FDA has given a “generally regarded as safe” (GRAS) rating.

“Many report fingernails growing faster and stronger, hair growing faster and better skin.”

*that means expensive

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Nicotinamide Riboside (NR) University of Washington trial for heart failure paients concludes in June

I recently read that the University of Washington Nicotinimide Riboside (NR) trial on heart failure patients will conclude in June. They could announce the results soon after or wait until a publication 6 to 12 months later. NR is a special derivative of vitamin B3 and has shown effectivenses against heart faiure in mice.

* a total of 30 participants with clinically stable, systolic heart failure (LVEF <40%) will undergo 2:1 randomization to NR 250mg PO twice daily or matching placebo

* NR (or matching placebo), will be increased weekly by 250mg/dose (500mg/day) to a final dose of 1000mg PO twice daily. Clinic visits with labs bi-weekly during dose escalation will assess HF symptoms and monitor labs [B-type natriuretic peptide (BNP), complete blood count (CBC), glycosylated hemoglobin, alanine aminotransferase (ALT), creatine kinase (CK), insulin/glucose, uric acid, electrolytes, blood urea nitrogen (BUN) and creatinine (Cr).

* Six-minute walk tests (6MWTs) at each visit (including Screening) to assess functional capacity B) Echocardiography at Baseline and Week 12 to assess LV systolic function (by real-time, 3D echocardiography) and diastolic function (by integrated Doppler and tissue Doppler imaging).

NR costs about $1.00 at 250 mg a day so $2.00 for 500 mg a day. A previous study unrelated to heart failure suggests that taking more than 500 mg a day boosts NAD+ levels only a bit more than 375 mg a day after the first month – around a 50% increase – whereas 250 mg a day provides a 40% sustained boost in NAD+. (125 mg of NR a day provides a 25% NAD boost.) That is for normal 60 to 80 year old non obese subjects. Trials have already demonstrated safety up to 1000mg a day. I've been taking 250mg for over a year.

The results from a University of Colorado NR trial with 30 subjects will be published soon and that includes before and after data for heart some heart effects as well.

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Window to expand treating strokes to 36 hours?

I remember being excited about the ability to treat strokes if a drug was administered within four hours of an event. Now it looks like it may soon expand to over a full day:

“Cleveland-based Athersys, with a market value of about $200 million, demonstrated evidence in a midstage trial that its therapy may be able to expand the emergency treatment window for major strokes to up to 36 hours, compared with about four hours with current drugs, potentially allowing many more patients to avoid crippling disabilities.”

See here for more details.

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What to make of NR?

I decided to type this up before the University of Colordo / Chromadex study is out at the end of this year or early next year when we will learn more about what the vitamin B3 supplement NR can do for us humans at 500 mg and 1000 mg, while the Elysium study showed effects of 250 mg and 500 mg although included pterostilbine as well.

I started to take 125 mg of NR last November at the age of 48 and soon noticed a change with sleep. Within a day or two, I felt my sleep was deeper and had vivid dreams as I had more often when younger. When I woke up, I was wide awake as well. Overall, I liked the changes, but it took a while to get used to.

From January, I began taking 250 mg of NR a day in the morning.

After six months, I got a haircut in April and when I rubbed my hand through my hair I could tell something was different: my hair was much thicker everywhere – in the back, on the sides and on top. I didn’t expect hair growth at all. I asked a 60 year old friend if he could tell that my hair was thicker, and he laughed: “It’s obvious!” His mostly gray/white hair had developed black streaks that became more pronounced after he took 250 mg of NR after six months and more so today at his one year mark. (He also thinks his nearsightdness has improved to when he was 40, but he hasn’t formally tested this yet with an optometrist.)

The Elysium study just published showed an almost 8% increase in the average distance walked in 6 minutes for healthy 60 to 80 year olds at 500 mg a day for 8 weeks but no increase at 250 mg. Likewise, there was a 7 to 8% average increase with a chair balance test at 500 mg but no impovement at 250 mg.

I expect to read about positive results with just 250 mg of NR a day but can also see that this might be marketed as a 375 mg and 500 mg supplement as well. Keep in mind that an obese person may find increased endurance at 250 mg as well since there metobolism is probably further from normal compared with non-obese people.

Bring on the U of Colorado results where cognitive function was measured as well!

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NR preserves cardiac function in a mouse model of heart failure

Looks like potetnial good news for heart failure patients

IRVINE, Calif., Dec. 14, 2017 (GLOBE NEWSWIRE) — ChromaDex Corp. (NASDAQ:CDXC), a fully integrated, science-based, nutraceutical company devoted to improving the way people age, announced important cardiac research by Dr. Mathias Mericksay and colleagues at the l’Université Paris-Sud, and Dr. Charles Brenner and colleagues at the University of Iowa, published in the journal Circulation. This research revealed that in a mouse model of heart failure, a loss of NAD levels is accompanied by activation of the nicotinamide riboside (NR) kinase pathway; administration of NIAGEN® in this model stabilizes NAD levels and leads to protective effects on cardiac function that may someday lead to a new therapeutic option for heart failure patients.

….In this new research, Drs. Mericksay, Brenner and colleagues discovered that in heart failure, activation of the NR kinase pathway, which occurs as a result of energy stress and NAD depletion is common to humans and mice. Because of activation of the NR kinase pathway, NR restores but nicotinamide fails to restore NAD levels. Measures of cardiac function are improved with oral administration of NR in this mouse model of heart failure.

Because the depression in NAD and the activation of the NR kinase pathway are common between humans and mice, the research strongly suggests that NIAGEN® may be capable of protecting against human heart failure….

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Elysium Basis human trial results published in Nature

Nature just published the results of the Elysium NR+pterostilbine study of 120 healthy 60 to 80 year olds with BMIs under 30.

1) 250 mg of NR and 50 mg of pterostilbine raised NAD+ levels by 40% for eight weeks in healthy 60 to 80 year olds. 500 mg of NR and 100 mg of pterostilbine raised NAD+ levels up to 90% after four weeks but steadily lowered to 55%. (The last part is new.)

2) Liver test: ASL went down while AST decreased but not with statsitical significance. A new trial is focusing on liver health.

3) There were very slight or no changes in heart rate, blood pressure, glucose levels or triglyceryde levels for both groups.

4) “Significantly” improved mobility with a 30 second chair-stand test and a 6 minute walk test for the 500 mg but *not* the 250 mg group. Unfortunately, the extent of the physical gains was not reported.

Next up: Elysium is focusing on liver health, brain health, cardiovascular, muscular disorders and diabetes in new separate studies. The U of Colorado study is also expected to be published in a few weeks.

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