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Vitamin B3/NAD Fully Prevents The Development Of Glaucoma In Mice And Halts Its Progression If Alrea

Discussion in 'Scientific Studies' started by PakPik, Feb 19, 2017.

  1. PakPik

    PakPik Member

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    Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice | Science

    "Oral administration of the NAD+ precursor nicotinamide (vitamin B3), and/or gene therapy (driving expression of Nmnat1, a key NAD+-producing enzyme), was protective both prophylactically and as an intervention. At the highest dose tested, 93% of eyes did not develop glaucoma. "

    "Vitamin B3 also halted further glaucoma development in aged mice that already showed signs of the disease."

    https://www.sciencedaily.com/releases/2017/02/170216143907.htm

    "The vitamin administration was surprisingly effective, eliminating the vast majority of age-related molecular changes and providing a remarkably robust protection against glaucoma."

    " In most glaucoma patients, harmfully high pressure inside the eye or intraocular pressure leads to the progressive dysfunction and loss of retinal ganglion cells. Retinal ganglion cells are the neuronal cells that connect the eye to the brain via the optic nerve. Increasing age is a key risk factor for glaucoma, contributing to both harmful elevation of intraocular pressure and increased neuronal vulnerability to pressure-induced damage."

    "Conducting a variety of genomic, metabolic, neurobiological and other tests in mice susceptible to inherited glaucoma, compared to control mice, the researchers discovered that NAD, a molecule vital to energy metabolism in neurons and other cells, declines with age."

    "The decrease in NAD levels reduces the reliability of neurons' energy metabolism, especially under stress such as increased intraocular pressure."

    "In essence, the treatments of vitamin B3 (nicotinamide, an amide form of vitamin B3, also called niacinamide) boosted the metabolic reliability of aging retinal ganglion cells, keeping them healthier for longer. "Because these cells are still healthy, and still metabolically robust," says JAX Postdoctoral Associate Pete Williams, first author of the study, "even when high intraocular pressure turns on, they better resist damaging processes.""
     
  2. SQu

    SQu Member

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    Thanks for posting!
     
  3. HempOil

    HempOil Member

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    Hi All,

    I am new to the world of niacinamide supplementation and came across this forum while doing some Google searches about this news story. I was wondering whether anyone could suggest what the human equivalent dosage would be of niacinamide to achieve the benefits seen in the study. I don't have access to the full study, but even if I did, I don't know whether I could do the conversion while also ensuring I supplement at a safe (yet still efficacious) level.

    Thanks!
     
  4. HempOil

    HempOil Member

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    Well, I found the following article on the Optometry Australia website (I cannot post links yet) that provides some guidance on dosage (40 grams/day). Having read through many of the niacinamide posts on this web site, I see that RP recommends a very low dose of 100-150mg/day. Meanwhile other posters use a few grams/day. I have my doubts that a dose of 40 grams/day is safe on an ongoing basis, so I would like to ask whether anyone on this forum has experimented at such high doses?



    optometry.org.au

    Vitamin could stop glaucoma

    Rhiannon Riches

    Associate Professor Ian Trounce Photo: CERA

    ______________________________

    By Helen Carter
    Journalist

    US research dubbed ‘an exciting breakthrough’ by a Melbourne vision scientist shows that vitamin B3 or nicotinamide can prevent glaucoma and stop progression of existing disease in animals.

    Although Associate Professor Ian Trounce from the Centre for Eye Research Australia described the findings as amazing, he suggested that optometrists should advise patients with glaucoma and those enquiring about glaucoma prevention against rushing out to buy the vitamin until trials in humans provided more answers.

    The research was published in Science, in the lead up to World Glaucoma Week next week.

    Professor Trounce, principal investigator at CERA’s Mitochondria Lab, and CERA’s managing director, glaucoma specialist Professor Jonathan Crowston were asked to write a commentary because of their research showing mitochondria changes in glaucoma cells.

    ‘They show that two interventions arrest disease progression in a mouse model of glaucoma,’ the professors wrote.

    Six months treatment as a preventive regime or three months as an interventional regime in those with glaucoma showed remarkable results at maintaining vision, they wrote.

    The US researchers reported that vitamin B3 prevented eye degeneration and glaucoma in glaucoma-prone mice. Supplementing diets of young mice with B3 averted early signs of glaucoma and halted further glaucoma development in aged mice showing signs of the disease.

    They identified decline in nicotinamide adenine dinucleotide (NAD+), a molecule vital to energy metabolism in neurons, as a key age-dependent risk factor and showed that restoration with long-term dietary supplementation or gene therapy robustly protects against neuronal degeneration.

    ‘We show that mitochondrial abnormalities are an early driver of neuronal dysfunction, occurring before detectable degeneration. Retinal levels of NAD+ and/or gene therapy were protective both prophylactically and as an intervention,’ they wrote.

    Vitamin B3 treatments (nicotinamide, an amide form of vitamin B3) boosted the metabolic reliability of ageing retinal ganglion cells, keeping them healthier for longer. Because the cells remain healthy and metabolically robust, even when high intraocular pressure turns on, they better resist damaging processes, they said.

    ‘At the highest dose tested, 93 per cent of eyes did not develop glaucoma. This supports therapeutic use of vitamin B3 in glaucoma and potentially other age-related neurodegenerations,’ they wrote.

    Very high dose supplementation increased the proportion of untreated eyes with no glaucomatous changes from under 70 per cent to 93 per cent and presented no safety concerns.

    One injection of gene therapy into the eye reversed degenerative changes in more than 70 per cent of treated eyes and was one of the first examples of gene therapy having a robust effect in a complex disease.

    Exciting breakthrough

    Professor Trounce told Australian Optometry: ‘I am averse to using this term but once I read the paper and saw there was no down-side, I would call it a breakthrough. It does seem really exciting and there appear to be no toxic down-sides.

    ‘It is a good mouse model of human-like glaucoma where at 12 months the mouse is in mid-life and develops very high pressure, making it prone to glaucoma. Mice were given vitamin B3 at nine months when the high pressure begins, a comparable age to glaucoma diagnosis in humans.

    ‘Results were remarkable, preventing development of glaucomatous changes, and when changes were noticed in mice, the glaucomatous changes were reversed after three months treatment. Mice at six months were also treated for six months and this was found to provide even better protection.’

    A second higher dose gave as good protection in preventing glaucoma, without toxic problems, but also reduced IOP.

    Gene therapy into the eye had the same effect as the supplement and when used with supplements led to a slightly better result than supplements alone. If developed, this may provide long-term or even life-long protection, Professor Trounce said.

    High doses

    Professor Trounce said doses equivalent to about 40 grams per day for an average weight human were given and no toxic effects were seen. Nicotinamide supplements for human use generally range from one-half to two grams per day, he said.

    ‘In the near future, if it holds up, there might be a high dose formula so people don’t have to take many capsules a day,’ he said.

    ‘The last thing we need is to be telling people to take massive doses of nicotinamide. It’s a common vitamin and we don’t want people clearing out the supermarket shelves. We need multicentre human trials to confirm findings in humans and ensure such high doses don’t have toxic effects.

    ‘The distinction between the nicotinamide form and Vitamin B3, also known as niacin, is important because taking large doses of niacin is known to cause discomforting skin rashes in many people. Nicotinamide does not have this problem.

    ‘Optometrists could tell patients they cannot recommend taking high doses because human trials have not been done but they can’t stop people taking multivitamins containing nicotinamide or including dietary sources.’

    Dietary sources of vitamin B3 include turkey, chicken breast, peanuts, mushrooms, liver, tuna, green peas, grass-fed beef, sunflower seeds and avocado.

    Professors Trounce and Crowston wrote that treatments that specifically target retinal ganglion cells or the effects of ageing on glaucoma susceptibility are lacking.

    They said the researchers reported ‘substantial advances toward filling these gaps by identifying NAD+ decline as a key age-dependent risk factor and showing that restoration with long-term dietary supplementation or gene therapy robustly protect from neuronal degeneration.’

    Unprecedented protection

    They wrote that the researchers ‘reveal unprecedented protection by a single molecule against a complex neurodegenerative disease.’

    They said the higher dietary dose reversed the ageing phenotype in the retina and protected retinal ganglion cells when eye pressure was increased but also decreased eye pressure in the glaucoma mouse model.

    ‘The widespread availability of NAD supplements and good tolerability make this a highly attractive treatment for translating into the clinic to augment existing therapies for decreasing eye pressure,’ they wrote.

    Professor Trounce said that for four years he had been gripped by increasing research showing profound positive effects of nicotinamide on mitochondria and he believed it may have more wide-ranging effects on general diseases of ageing, not just the ageing eye.

    ‘Mitochondria were struggling and disorganised in untreated mice but healthy in treated mice,’ he said.

    He said vitamin B3 could potentially be an adjunct therapy to IOP drops or surgery.

    The US researchers are pursuing clinical partnerships to test the therapy in glaucoma patients.

    Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice

    Glaucoma Australia encourages people to plan their own BIG (Beat Invisible Glaucoma) Breakfast during World Glaucoma Week from 12 to 18 March.
     
  5. OP
    PakPik

    PakPik Member

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    Thanks so much for sharing!
    40 grams daily... That's a huge dose. I personally wouldn't take that dose for a glaucoma. It can be too much for the liver -and for the whole body-. The paper you cited claims that the glaucoma-protective effect is mediated by an increase in NAD+. If I'm not wrong, forum member Haidut has posted some studies showing that niacinamide in low doses can lead to increased NAD+. Maybe low doses of niacinamide can still be protective that way -due to NAD+ increase-, but unfortunately the study didn't test the effect of low doses of niacinamide on glaucoma, so it's hard to know.
     
  6. HempOil

    HempOil Member

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    Happy to share. Perhaps, Haidut can join the conversation as well.

    I agree about the potential risks of large doses. Unfortunately, I think the crux of the article was that the higher the dose, the more effective it is against glaucoma.

    I found some good info on recommended doses for the general population:

    The following information comes from the Vitamin and Mineral Safety 3 rd Edition (2013) Council for Responsible Nutrition (CRN):

    Bioavailability

    Escalating oral doses of 3, 4, 5, 6, and 10 g of nicotinamide showed a linear relationship between maximum recorded plasma concentrations and the dose in grams. Maximum plasma levels were observed by 30 minutes in most patients ingesting up to 6 g of nicotinamide. Doses up to 6 g were well tolerated and resulted in average maximum recorded plasma levels (mean ± 1 SEM) of 156.4 ± 33.6 µg per ml. Doses of 10 g were generally not well tolerated, but a high plasma level was maintained on average for at least 4 hour (Dragovic 1995).

    Safety Considerations

    Nicotinamide does not cause a flushing reaction. The 1998 study by the IOM’s Food and Nutrition Board (FNB) study determined a LOAEL for vasodilatation and the flushing effect from nicotinic acid; but they then, unfortunately, applied that LOAEL to both nicotinic acid and nicotinamide. Later studies by EFSA and the EVM corrected this error.

    CRN Recommendations

    There is much less information on nicotinamide than there is for nicotinic acid, but there also appears to be much less use at high levels of intake. Clinical trials on high-dose nicotinamide have been small. One study observed no adverse effects in 16 subjects who received 3,000 mg of nicotinamide per day (Vague et al. 1987), but the method of monitoring for such effects was not specified. Other studies that describe monitoring methods in more detail have found no adverse effects for nicotinamide intakes in the range of 1,000 to 2,900 mg per day (Mendola et al. 1989; Chase et al. 1990; Pozzili et al. 1995; Lampeter et al. 1998). Nicotinamide intakes of more than 3,000 mg per day have resulted in adverse gastrointestinal and liver effects (Rader et al. 1992).

    The clinical trial results support a very confident NOAEL of 25 mg per kg per day. Because some of these trials were performed with subjects aged younger than 18 years who had lower than fully adult body weights, 60 kg was used to calculate a NOAEL of 1,500 mg per day. The absence of adverse effects in clinical trials that included nicotinamide dosages of up to 3,000 mg per day reduces the uncertainty in this value.

    CRN identifies the following LOAEL and NOAEL values

    LOAEL 3,000 mg/day
    NOAEL 1,500 mg/day
    Flush label warning threshold Not needed

    Quantitative Summary

    CRN UL, supplemental intake 1,500 mg/day
    IOM UL, total intake 35 mg/day
    EC SCF UL, total intake 900 mg/day
    EC supplement maximum Not determined
    EVM, guidance level 500 mg/day supplemental intake;
    560 mg/day total intake
     
  7. OP
    PakPik

    PakPik Member

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    Thank you @HempOil. I've taken doses of nicotinamide ranging form low to high, but never something like 40 grams. That's way too much in my book and from what I've researched about niacinamide.
    I think if you use the search function of the forum you can locate the niacinamide increasing NAD+ posts.
     
  8. HempOil

    HempOil Member

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    Thanks @PakPik, I'll try the search you suggest.

    I found a copy of the study and the amounts used are even more ridiculous at the high dose:

    Low dose:
    550 mg/kilogram of body weight per day, NAM
    Resulted in ~60-75% of treated eyes having no optic nerve damage (my estimate from a chart; actual percentages were not quantified in the text).

    High dose:
    Attempting to further decrease the probability of glaucoma, we administered a higher dose of NAM (2000 mg/kg per day, NAM). NAM was extremely protective, with 93% of treated eyes having no optic nerve damage

    I weigh 140lbs, so my range would be ~35 grams/day on the low dose or 127 grams/day on the high dose!!!
     
  9. SQu

    SQu Member

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    Wow! I'm very, very interested in avoiding glaucoma but more than 100mg a day gives me irregular heartbeat.
     
  10. HempOil

    HempOil Member

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    Perhaps, a better idea is to look into safer alternatives to niacinamide that also increase NAD+?
     
  11. HempOil

    HempOil Member

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    Well, it seems that I should have used a compensating value to come up with a Human Equivalent Dose (HED). It is not 1:1 with animals (refer to chart). One can either divide the mouse dose by 1.3 or multiply the mouse dose by .081. So my revised numbers would be as follows:

    I weigh 140lbs, so my range would be ~2.8 grams/day on the low dose or ~10 grams/day on the high dose. Clearly, the low dose is now realistic.
     
  12. OP
    PakPik

    PakPik Member

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    Yeah, conversions need to be done to calculate human value. I kind of got caught up in the "40 grams" figure for humans I read in the article you shared and thought it represented the converted dose. Great to know that 40 grams figure wasn't referring to a human equivalent from the experiment, and it is much lower!
     
  13. tankasnowgod

    tankasnowgod Member

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    Since it seems that NAD+ itself is protective, you could also use Red Light and Methylene Blue, and a lower dose of Niacinamide. All three generate NAD+, I think through different mechanisms.
     
  14. SQu

    SQu Member

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    good idea, thanks

    quick look at self-hacked suggests a number of things, of which I might look further into these few: fructose (interesting, desire for sugar) apigenin, malic acid, leucine, lithium. Just going to mull these over for a bit
     
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