537 replies to this topic

[Heisok]

Good points Castiel. I take my BroccoMax with another product which claims 24 mgs glucosinolates per capsule. Before taking the capsules, I chew on some brown mustard seeds. Do not know how effective this can be.

 

Nate-2004, thanks for the Jarrow information that the myrosinase is from Broccoli. I chewed on a couple BroccoMax capsules, and the taste was very similar to brown mustard seeds. I wondered.

[ironfistx]

I conceal a bottle of Broccomax. It says on the site that it was checked in vitro.

[Turnbuckle]

From the OP--

 

Now, I propose that if we were to ask researchers to study any anti-aging combination, it should be Sulforaphane and Nicotinamide Riboside. The combination could potentially produce EXTREMELY synergistic results.

 

 

I think it's likely to be the opposite. NR and other NAD+ precursors get the mitochondrial quality control system running, whereby dysfunctional mitochondria are tagged, engulfed by lysosomes, and digested. To fit them into lysosomes they must be fissioned into the smallest possible size, and then later they fuse together to produce mitochondria that are more robust than before. So anything that prevents fission is going to reduce or eliminate the effectiveness of NR. And sulforaphane is a promoter of "hyperfusion," which means they are even larger than normal. Thus these supplements are working at cross purposes.

 

See this paper--

 

We demonstrate here that SFN [Sulforaphane] induces mitochondrial hyperfusion . . .

https://www.ncbi.nlm...les/PMC5126150/

 

 

 

So unless someone is getting amazing results with this combination (I doubt it), I wouldn't take them at the same time. And I wouldn't take either supplement all the time.

 

[Andey]

From the OP--

 

Now, I propose that if we were to ask researchers to study any anti-aging combination, it should be Sulforaphane and Nicotinamide Riboside. The combination could potentially produce EXTREMELY synergistic results.

 

 

I think it's likely to be the opposite. NR and other NAD+ precursors get the mitochondrial quality control system running, whereby dysfunctional mitochondria are tagged, engulfed by lysosomes, and digested. To fit them into lysosomes they must be fissioned into the smallest possible size, and then later they fuse together to produce mitochondria that are more robust than before. So anything that prevents fission is going to reduce or eliminate the effectiveness of NR. And sulforaphane is a promoter of "hyperfusion," which means they are even larger than normal. Thus these supplements are working at cross purposes.

 

 

    Its somewhat common that NR have immediate effect like more energy and awareness (in anecdotal terms) within hours after administration. Some people could not sleep if it was taken in the evening.

 Can it be attributed to the action you described or may be its too fast for that and there is something else going on besides mitochondrial quality control system activation ?

Edited by Andey, 09 March 2017 - 01:34 PM.

[Turnbuckle]

 

 

 

    Its somewhat common that NR have immediate effect like more energy and awareness (in anecdotal terms) within hours after administration. Some people could not sleep if it was taken in the evening.

 Can it be attributed to the action you described or may be its too fast for that and there is something else going on besides mitochondrial quality control system activation ?

 

 

 

Sure. NAD+ and NADH are central to energy production by mitochondria and act as substrates for important enzymes, so many people will see a boost of energy. See Wikipedia for more. As for mito QC, it's the ratio NAD+/NADH that's important, and taking nicotinamide, NR or niacin will boost that ratio as well--

 

Active autophagy coupled with rapid mitochondrial fusion and fission constitutes an important mitochondrial quality control mechanism and is critical to cellular health. In our previous studies, we found that exposure of cells to nicotinamide causes a decrease in mitochondrial content and an increase in mitochondrial membrane potential (MMP) by activating autophagy and inducing mitochondrial fragmentation. Here, we present evidence to show that the effect of nicotinamide is mediated through an increase of the [NAD+]/[NADH] ratio and the activation of SIRT1, an NAD+-dependent deacetylase that plays a role in autophagy flux. The [NAD+]/[NADH] ratio was inversely correlated with the mitochondrial content...

 

https://www.ncbi.nlm...pubmed/22493485

 

 

[Andey]

Sure. NAD+ and NADH are central to energy production by mitochondria and act as substrates for important enzymes, so many people will see a boost of energy. See Wikipedia for more. As for mito QC, it's the ratio NAD+/NADH that's important, and taking nicotinamide, NR or niacin will boost that ratio as well--

 

Active autophagy coupled with rapid mitochondrial fusion and fission constitutes an important mitochondrial quality control mechanism and is critical to cellular health. In our previous studies, we found that exposure of cells to nicotinamide causes a decrease in mitochondrial content and an increase in mitochondrial membrane potential (MMP) by activating autophagy and inducing mitochondrial fragmentation. Here, we present evidence to show that the effect of nicotinamide is mediated through an increase of the [NAD+]/[NADH] ratio and the activation of SIRT1, an NAD+-dependent deacetylase that plays a role in autophagy flux. The [NAD+]/[NADH] ratio was inversely correlated with the mitochondrial content...

 

https://www.ncbi.nlm...pubmed/22493485

 

 

 

Thanks. Thats an important point to consider.

 

[ironfistx]

After having taken .5 capsules the other day and 1 capsule yesterday and one earlier, I feel a bit sluggish.

[Nate-2004]

After having taken .5 capsules the other day and 1 capsule yesterday and one earlier, I feel a bit sluggish.

 

How much do you weigh? How small are you? .5 isn't going to do anything really. You were likely sluggish and tired because of anything else but that. Lack of sleep, something you ate, etc.

 

If anything, 2 or 3 caps of BroccoMax should give anyone more energy than they can handle. 

[DareDevil]

 

A synthetic form of sulforaphane

http://www.evaluateg...Story&id=534658

Hi Cube,

 

This Irish product isn't yet on the market, however it is said to contain a dosage of 43mg/capsule of sulforaphane. While some say it is very low, maybe it depends on the bioavailability of various forms of sulforaphane?

 

For example this French one, declared by another Longecity member to have 70% bioavailability, is dosed at only 10mg/capsule. They say to not exceed 30mg to 60mg/day:

 

http://www.prostapha...rostaphane.html

 

I would like to better understand what target dosage might be useful. I plan to buy a pack of 90 capsules and test Prostaphane at various doses.

 

Cheers,

 

DareDevil

 

 

I just received delivery of the following product and plan to try it. It came delivered with an ice-pack and was still cold when I placed it in the fridge.

 

 

http://www.vitalya.f...0cp-p-9132.html

 

By some strange coincidence, I stopped taking NR a few weeks ago due to digestive side effects. I had been taking NR at 250mg/day along with 15mg of MitoQ. I in fact stopped taking either NR or MitoQ after that. From the latest news this might be a good thing if, in fact, it turns out that NR shouldn't be taken together with Sulforaphane?

 

I will be starting with 3 capsules of Prostophane equal to 30mg/day of Sulforaphane. I am wondering if I had best take it alone, or maybe with MitoQ or another supplement? Synergetic effects would be nice, but otherwise I will avoid complicating things unless there's a potentiator for the Sulforaphane to get higher effectiveness? For example in my fridge I have an unopened bottle of Methyl Blue I planned to try in intranasal spray.

 

.... low dose Methylene Blue (10 mg) since it can cross easily the BBB, activates Sirt1 and AMPK.

https://www.ncbi.nlm...les/PMC5034653/
 

 

This is my first attempt with a purified pharmaceutical form of Sulforaphane.

Thanks for your advice on dosages and experimental combinations.

 

DareDevil

Edited by DareDevil, 10 March 2017 - 05:05 AM.

[Harkijn]

I don't think this research was linked to yet. More good news about SFN:

https://www.scienced...70307100402.htm

[Richard McGee]

From the OP--

 

Now, I propose that if we were to ask researchers to study any anti-aging combination, it should be Sulforaphane and Nicotinamide Riboside. The combination could potentially produce EXTREMELY synergistic results.

 

 

I think it's likely to be the opposite. NR and other NAD+ precursors get the mitochondrial quality control system running, whereby dysfunctional mitochondria are tagged, engulfed by lysosomes, and digested. To fit them into lysosomes they must be fissioned into the smallest possible size, and then later they fuse together to produce mitochondria that are more robust than before. So anything that prevents fission is going to reduce or eliminate the effectiveness of NR. And sulforaphane is a promoter of "hyperfusion," which means they are even larger than normal. Thus these supplements are working at cross purposes.

 

See this paper--

 

We demonstrate here that SFN [Sulforaphane] induces mitochondrial hyperfusion . . .

https://www.ncbi.nlm...les/PMC5126150/

 

 

 

So unless someone is getting amazing results with this combination (I doubt it), I wouldn't take them at the same time. And I wouldn't take either supplement all the time.

 

Should we extend this observation to include other similar compounds that might be working against each other? Perhaps one of our knowledgeable posters could compile a chart listing compounds that are compatible (to be taken concurrently) and those that are incompatible (to be taken separately).

 

You mentioned mitochondrial fission and fusion. Are there other processes affected by supplementation that might lead to such conflicts?

[Turnbuckle]

 

You mentioned mitochondrial fission and fusion. Are there other processes affected by supplementation that might lead to such conflicts?

 

 

 

There may well be other factors to consider, such as which genes are being turned on and off (like PINK1 and Parkin).

 

There's also the stress on mitochondria. Exercise should put strain on mitochondria and make NAD QC more efficient. I've personally found that NAD supplements seem to magnify the effect of exercise and it's easy to go to far with it. Fasting and diet will likely have an effect, as will antioxidants. Antioxidants will likely decrease the value of NAD supplements for the same reason some muscle builders avoid them during exercise, as they will shield defective mitochondria from the QC mechanism thus reducing the ATP generating ability of the cell. See here. This may not apply to all anti-oxidants, but I've personally noted that a strong antioxidant like C60 allows me to lift far more weight without any subsequent muscle soreness, yet has little apparent benefit for building muscle. 

[j87]

After having taken .5 capsules the other day and 1 capsule yesterday and one earlier, I feel a bit sluggish.

 

 

 

After having taken .5 capsules the other day and 1 capsule yesterday and one earlier, I feel a bit sluggish.

 

How much do you weigh? How small are you? .5 isn't going to do anything really. You were likely sluggish and tired because of anything else but that. Lack of sleep, something you ate, etc.

 

If anything, 2 or 3 caps of BroccoMax should give anyone more energy than they can handle. 

 

My dad and I both feel similar effects from 2 capsules of broccomax, I feel doped up for a couple hours afterward. The guy from selfhacked reported something similar in his blog post from eating sprouts.

[DareDevil]

Thanks for the new information. I stumbled upon a controversial declaration.

Point 5 of the following analysis indicates that Nicotinamide accelerates aging?

 

 

http://www.anti-agin...life-extension/

 

 

QUOTE:

 

 

5.  Nicotinamide (Nam)

Nicotinamide is a direct inhibitor of both the SIRT enzymes and the PARP enzymes.

The accumulation of excess nicotinamide in cells is probably a major cause of aging.  Whereas we typically associate “NAD deficiency” with aging, “Nam excess” may have a similar effect.  To no one’s surprise, the levels of the two compounds are inversely related in aging.

Nam plays a role in both aging and in disease.   In hypertension and in aging individuals with normal blood pressure, Nam inhibits the methylation-mediated degradation of catecholamines.  Thus Nam excess plays a role in hypertension (see references below).

Nicotinamide also has an epigenetic effect. When SIRT1 is inhibited, cells age and cancer oncogenes are re-activated.  SIRT1 silences these genes  by histone deacetylation of H3K9 and H4K16 residues on the histones of these oncogenes.

A recent article showed that in rats, nicotinamide supplementation during pregnancy causes global DNA hypomethylation in rat fetuses.  Nicotinamide has detrimental effects in development, detrimental metabolic effects, and detrimental epigenetic effects when given to young rats.  Low dose nicotinamide increased weight gain in developing rats.  High dose nicotinamide did not, however.  The livers of nicotinamide-fed young rats had more DNA damage (8oxoG), impaired glucose tolerance, and increased insulin resistance.  Nicotinamide increased the levels of N-methylnicotinamide in the blood and decreased betaine levels in the blood.  This resulted in a global hypomethylation of DNA in the rat genome.  Nicotinamide also had “gene-specific effects” on CpG islands within the promoters of the following genes:

1. NNMT gene – this was down-regulated
2. DNMT genes – these were down-regulated
3. Homocysteine metabolism genes – these were down-regulated
4. Antioxidant genes and oxidative stress protection genes – these were down-regulated

Since niacin is converted into nicotinamide in human tissues, high dose niacin probably produces all of the above effects.  A recent paper called niacin and nicotinic acid “methyl consumers” and strongly suggested that high niacin/nicotinic acid intake is bad.

Excess nicotinamide has also been shown to increase plasma serotonin and histamine levels in humans, due to disrupting the metabolism of these neurotransmitters.  This is probably due to the fact that methyl donors and methylation enzymes are needed for serotonin/histamine metabolism.   Most importantly, nicotinamide is a direct inhibitor of the Sirtuin enzymes (SIRT1-7) and the PARP enzymes (all 17 of the PARPs).

The molecular mechanism by which Nam works is very straightforward. Nam acts as a direct inhibitor of the SIRT1 enzyme pocket where NAD binds.  Thus Nam is a “competitive inhibitor” of NAD and is “bad” when it comes to most cancers, aging, and most diseases.

 

[Nate-2004]

Thanks for the new information. I stumbled upon a controversial declaration.

Point 5 of the following analysis indicates that Nicotinamide accelerates aging?

 

 

http://www.anti-agin...life-extension/

 

 

QUOTE:

 

 

5.  Nicotinamide (Nam)

Nicotinamide is a direct inhibitor of both the SIRT enzymes and the PARP enzymes.

The accumulation of excess nicotinamide in cells is probably a major cause of aging.  Whereas we typically associate “NAD deficiency” with aging, “Nam excess” may have a similar effect.  To no one’s surprise, the levels of the two compounds are inversely related in aging.

Nam plays a role in both aging and in disease.   In hypertension and in aging individuals with normal blood pressure, Nam inhibits the methylation-mediated degradation of catecholamines.  Thus Nam excess plays a role in hypertension (see references below).

Nicotinamide also has an epigenetic effect. When SIRT1 is inhibited, cells age and cancer oncogenes are re-activated.  SIRT1 silences these genes  by histone deacetylation of H3K9 and H4K16 residues on the histones of these oncogenes.

A recent article showed that in rats, nicotinamide supplementation during pregnancy causes global DNA hypomethylation in rat fetuses.  Nicotinamide has detrimental effects in development, detrimental metabolic effects, and detrimental epigenetic effects when given to young rats.  Low dose nicotinamide increased weight gain in developing rats.  High dose nicotinamide did not, however.  The livers of nicotinamide-fed young rats had more DNA damage (8oxoG), impaired glucose tolerance, and increased insulin resistance.  Nicotinamide increased the levels of N-methylnicotinamide in the blood and decreased betaine levels in the blood.  This resulted in a global hypomethylation of DNA in the rat genome.  Nicotinamide also had “gene-specific effects” on CpG islands within the promoters of the following genes:

1. NNMT gene – this was down-regulated
2. DNMT genes – these were down-regulated
3. Homocysteine metabolism genes – these were down-regulated
4. Antioxidant genes and oxidative stress protection genes – these were down-regulated

Since niacin is converted into nicotinamide in human tissues, high dose niacin probably produces all of the above effects.  A recent paper called niacin and nicotinic acid “methyl consumers” and strongly suggested that high niacin/nicotinic acid intake is bad.

Excess nicotinamide has also been shown to increase plasma serotonin and histamine levels in humans, due to disrupting the metabolism of these neurotransmitters.  This is probably due to the fact that methyl donors and methylation enzymes are needed for serotonin/histamine metabolism.   Most importantly, nicotinamide is a direct inhibitor of the Sirtuin enzymes (SIRT1-7) and the PARP enzymes (all 17 of the PARPs).

The molecular mechanism by which Nam works is very straightforward. Nam acts as a direct inhibitor of the SIRT1 enzyme pocket where NAD binds.  Thus Nam is a “competitive inhibitor” of NAD and is “bad” when it comes to most cancers, aging, and most diseases.

 

DareDevil this is old news and why people take NR instead.

[Turnbuckle]

 

 

 

DareDevil this is old news and why people take NR instead.

 

 

 

I thought most people took it because of the marketing, based on results obtained on one person--the inventor himself. Only last year was a larger human trial done, and that one was only 12 people (with a week between doses), and was mainly to assess safety. The inventor did that study as well. 

 

They previously compared these various NAD+ precursors in mice, and found the following according to the link above--

 

In particular, the researchers compared the ability of all three NAD+ precursor vitamins—NR, niacin, and nicotinamide—to boost NAD+ metabolism and stimulate the activity of certain enzymes, which have been linked to longevity and health benefits. The study showed for the first time that oral NR is superior to nicotinamide, which is better than niacin in terms of the total amount of NAD+ produced at an equivalent dose. NR was also the best of the three in stimulating the activity of sirtuin enzymes. However, in this case, NR was the best at stimulating sirtuin-like activities, followed by niacin, followed by nicotinamide.

 

 

 

So presumably, one could simply take more nicotinamide, or take it with ribose and let your body do the chemistry. Here is the latest paper in which the inventor looked the responses at doses up to 1 gm NR, as well as niacin and nicotinamide. The inventor shows a lot of plots of NAD+ over time, but he doesn't have any for the NAD+/NADH ratio, which is the driver for mito QC, and which should be of primary interest to anyone who wants to improve their mitochondrial health.

 

I've been experimenting with 2 g nicotinamide combined with a few grams of ribose (not continuously), and considering its dramatic magnifying effect on exercise, I haven't seen any need to take more. As for the possible negatives of nicotinamide, none of these NAD+ precursors should be taken all the time, if you're looking for maximum benefit. If evolution had found a benefit for jacking up the NAD+/NADH ratio continuously, it would be naturally higher than it is. 

 

Edited by Turnbuckle, 11 March 2017 - 11:58 AM.

[DareDevil]

 

Thanks for the new information. I stumbled upon a controversial declaration.

Point 5 of the following analysis indicates that Nicotinamide accelerates aging?

 

DareDevil this is old news and why people take NR instead.

 

Thanks Nate,

 

I'm guilty of confusing Nicotinamide (NAA) with Nicotinamide Riboside (NR)

 

All my apologies

 

DD

[Nate-2004]

 

 

 

 

DareDevil this is old news and why people take NR instead.

 

 

 

I thought most people took it because of the marketing, based on results obtained on one person--the inventor himself. Only last year was a larger human trial done, and that one was only 12 people (with a week between doses), and was mainly to assess safety. The inventor did that study as well. 

 

They previously compared these various NAD+ precursors in mice, and found the following according to the link above--

 

In particular, the researchers compared the ability of all three NAD+ precursor vitamins—NR, niacin, and nicotinamide—to boost NAD+ metabolism and stimulate the activity of certain enzymes, which have been linked to longevity and health benefits. The study showed for the first time that oral NR is superior to nicotinamide, which is better than niacin in terms of the total amount of NAD+ produced at an equivalent dose. NR was also the best of the three in stimulating the activity of sirtuin enzymes. However, in this case, NR was the best at stimulating sirtuin-like activities, followed by niacin, followed by nicotinamide.

 

 

 

So presumably, one could simply take more nicotinamide, or take it with ribose and let your body do the chemistry. Here is the latest paper in which the inventor looked the responses at doses up to 1 gm NR, as well as niacin and nicotinamide. The inventor shows a lot of plots of NAD+ over time, but he doesn't have any for the NAD+/NADH ratio, which is the driver for mito QC, and which should be of primary interest to anyone who wants to improve their mitochondrial health.

 

I've been experimenting with 2 g nicotinamide combined with a few grams of ribose (not continuously), and considering its dramatic magnifying effect on exercise, I haven't seen any need to take more. As for the possible negatives of nicotinamide, none of these NAD+ precursors should be taken all the time, if you're looking for maximum benefit. If evolution had found a benefit for jacking up the NAD+/NADH ratio continuously, it would be naturally higher than it is. 

 

 

No, we take it because it's a step ahead of NAM in the process of becoming NAD+. It skips over the part where it can inhibit SIRT. Also, there are newer published studies than that one study you mention, you might want to catch up on the NR Curated thread. Certainly more research is needed but even just in theory it's a better option and the research is certainly a lot more robust and positive than any of the one fluke research study on C60.

 

P.S. That's not how evolution works.

Edited by Nate-2004, 11 March 2017 - 02:41 PM.

[Turnbuckle]

 

 

No, we take it because it's a step ahead of NAM in the process of becoming NAD+. It skips over the part where it can inhibit SIRT. Also, there are newer published studies than that one study you mention, you might want to catch up on the NR Curated thread. Certainly more research is needed but even just in theory it's a better option and the research is certainly a lot more robust and positive than any of the one fluke research study on C60.

 

P.S. That's not how evolution works.

 

 

 

No, we take it because it's a step ahead of NAM in the process of becoming NAD+.

 

That's been the marketing pitch since early on, but so what? The bottom line for mito QC is the ratio of NAD+/NADH and the resulting increase of mitophagy. Can you point me to a paper that addresses that? 

 

It skips over the part where it can inhibit SIRT.

 

That's probably not a concern for intermittent use (or for low dose use), or for co-use with ribose. For use to protect hearing (and perhaps for neurons in general) NR seems advantageous as it actually promotes SIRT3. See the following study involving rodents, which suggests that NR is indeed superior for neurons--

We find that administration of NR, even after noise exposure, prevents noise-induced hearing loss (NIHL) and spiral ganglia neurite degeneration. These effects are mediated by the NAD+-dependent mitochondrial sirtuin, SIRT3, since SIRT3-overexpressing mice are resistant to NIHL and SIRT3 deletion abrogates the protective effects of NR and expression of NAD+ biosynthetic enzymes. These findings reveal that administration of NR activates a NAD+-SIRT3 pathway that reduces neurite degeneration caused by noise exposure.

 

https://www.ncbi.nlm...les/PMC4940130/

 

 

Now the question remains--and it has been debated on other threads--is NR absorbed as NR or as NAM + ribose. If the latter, then there is no reason to take the far more expensive NR. The following research suggests that NR is not absorbed as such but is broken down. In the study, retroactively labeled NAD was broken down in several steps in rats until it became NR, which was further broken down in the digestive system--

 ... to nicotinamide riboside, which accumulated, but was not absorbed. It was slowly cleaved by an enzyme associated with the mucosal cells to nicotinamide, which was the major if not the only labeled compound absorbed.

 

http://www.jbc.org/c...6/3701.full.pdf

 

 

 

Also, there are newer published studies than that one study you mention

 

The human trial I linked to is from 2016 Oct 10. Can you link to a human study subsequent to that? 

 

That's not how evolution works

 

Really? You don't think biological set-points are heritable if they give the organism an advantage?

Edited by Turnbuckle, 11 March 2017 - 04:40 PM.

[Harkijn]

 ... to nicotinamide riboside, which accumulated, but was not absorbed. It was slowly cleaved by an enzyme associated with the mucosal cells to nicotinamide, which was the major if not the only labeled compound absorbed.

 

http://www.jbc.org/c...6/3701.full.pdf

 

 

 Really? A fifty year old study about injecting radioactive nicotinamide in the portal vein? Ah well, noone will argue against you if you want to take NAM plus riboside. If it works for you, just do it!

 

 

 

[Turnbuckle]

 

 ... to nicotinamide riboside, which accumulated, but was not absorbed. It was slowly cleaved by an enzyme associated with the mucosal cells to nicotinamide, which was the major if not the only labeled compound absorbed.

 

http://www.jbc.org/c...6/3701.full.pdf

 

 

 Really? A fifty year old study about injecting radioactive nicotinamide in the portal vein? Ah well, noone will argue against you if you want to take NAM plus riboside. If it works for you, just do it!

 

 

Sorry. I had two old PDFs open and I linked to the wrong one. As it's now too late to fix it, here is the correct PDF--

 

http://nadh.wiki/wp-...-of-the-Rat.pdf

 

Note that if NR is broken down in the gut and then reassembled, some ribose will be lost and thus taking NAM with excess ribose should give better results.

Edited by Turnbuckle, 11 March 2017 - 06:00 PM.

[Oakman]

Hey guys, I've lost all sense of "the answer" in this thread, amongst all the back and forth. Maybe it's time for a summary....

 

Wasn't the original question...

 

"Sulforaphane and Nicotinamide Riboside: The best combination for maximizing AMPK and the (sic) SIRTULINS?" 

 

So ultimately...

 

1) is it good or bad (or neither) to mix NR and Sulforaphane? (Y or N or ?)

2) If Yes, then what is the ratio NR/sulforaphane and amounts of sulforaphane to be used with NR? (the original ?)

 

I've got plenty of each, I've read a lot of this thread, but am left wondering if there is a consensus answer or just continued controversy (among the 290 replies so far)!

[Turnbuckle]

Hey guys, I've lost all sense of "the answer" in this thread, amongst all the back and forth. Maybe it's time for a summary....

 

Wasn't the original question...

 

"Sulforaphane and Nicotinamide Riboside: The best combination for maximizing AMPK and the (sic) SIRTULINS?" 

 

So ultimately...

 

1) is it good or bad (or neither) to mix NR and Sulforaphane? (Y or N or ?)

2) If Yes, then what is the ratio NR/sulforaphane and amounts of sulforaphane to be used with NR? (the original ?)

 

I've got plenty of each, I've read a lot of this thread, but am left wondering if there is a consensus answer or just continued controversy (among the 290 replies so far)!

 

It's bad. See post 273.

[Oakman]

 

Hey guys, I've lost all sense of "the answer" in this thread, amongst all the back and forth. Maybe it's time for a summary....

 

Wasn't the original question...

 

"Sulforaphane and Nicotinamide Riboside: The best combination for maximizing AMPK and the (sic) SIRTULINS?" 

 

So ultimately...

 

1) is it good or bad (or neither) to mix NR and Sulforaphane? (Y or N or ?)

2) If Yes, then what is the ratio NR/sulforaphane and amounts of sulforaphane to be used with NR? (the original ?)

 

I've got plenty of each, I've read a lot of this thread, but am left wondering if there is a consensus answer or just continued controversy (among the 290 replies so far)!

 

It's bad. See post 273.

 

Great...fission and hyperfusion are incompatible. So if we want to take both (separately), anyone have suggestions on timing?

 

Say filling in the variables in this sentence, "If taking NR, do a washout for X days, then Y days take Z mg sulforaphane/day, then wash out W days and restart NR?

 

Obviously, pretty much opinion at this point (or maybe you have references), but has anyone tried doing anything like this and how did it play out?

[Andey]

Am I wrong that NR and sulforaphane works on a different levels in the 'chain of command' ?

Sulforophane is a hormetic compound (accordingly to dr Ronda Patrick) and its action is a body response to a unique stress factor that triggers favorable gene expression. BTW mitochondrial fusion is just a one of hundreds of its outcomes.

NR|NAD works at a low level of cell processes. As for me most probably excess NAD will override easily any sulforaphane influence because it works on a lower, basic level of cell mechanics.

No way IMHO you take 2gr of niacin and few cups of broccoli would stop its action (its quite easy to check BTW) 

 

P.S No doubt though that almost any supplement should be cycled.

Edited by Andey, 11 March 2017 - 08:35 PM.

[Nate-2004]

 

 

 

No, we take it because it's a step ahead of NAM in the process of becoming NAD+. It skips over the part where it can inhibit SIRT. Also, there are newer published studies than that one study you mention, you might want to catch up on the NR Curated thread. Certainly more research is needed but even just in theory it's a better option and the research is certainly a lot more robust and positive than any of the one fluke research study on C60.

 

P.S. That's not how evolution works.

 

 

 

No, we take it because it's a step ahead of NAM in the process of becoming NAD+.

 

That's been the marketing pitch since early on, but so what? The bottom line for mito QC is the ratio of NAD+/NADH and the resulting increase of mitophagy. Can you point me to a paper that addresses that? 

 

It skips over the part where it can inhibit SIRT.

 

That's probably not a concern for intermittent use (or for low dose use), or for co-use with ribose. For use to protect hearing (and perhaps for neurons in general) NR seems advantageous as it actually promotes SIRT3. See the following study involving rodents, which suggests that NR is indeed superior for neurons--

We find that administration of NR, even after noise exposure, prevents noise-induced hearing loss (NIHL) and spiral ganglia neurite degeneration. These effects are mediated by the NAD+-dependent mitochondrial sirtuin, SIRT3, since SIRT3-overexpressing mice are resistant to NIHL and SIRT3 deletion abrogates the protective effects of NR and expression of NAD+ biosynthetic enzymes. These findings reveal that administration of NR activates a NAD+-SIRT3 pathway that reduces neurite degeneration caused by noise exposure.

 

https://www.ncbi.nlm...les/PMC4940130/

 

 

Now the question remains--and it has been debated on other threads--is NR absorbed as NR or as NAM + ribose. If the latter, then there is no reason to take the far more expensive NR. The following research suggests that NR is not absorbed as such but is broken down. In the study, retroactively labeled NAD was broken down in several steps in rats until it became NR, which was further broken down in the digestive system--

 ... to nicotinamide riboside, which accumulated, but was not absorbed. It was slowly cleaved by an enzyme associated with the mucosal cells to nicotinamide, which was the major if not the only labeled compound absorbed.

 

http://www.jbc.org/c...6/3701.full.pdf

 

 

 

Also, there are newer published studies than that one study you mention

 

The human trial I linked to is from 2016 Oct 10. Can you link to a human study subsequent to that? 

 

That's not how evolution works

 

Really? You don't think biological set-points are heritable if they give the organism an advantage?

 

 

I don't see how mito QC is relevant to my point that marketing or not, it is a fact that NR is 2 steps from NAD+, and if it's true that it makes it all the way into the cell as NR, then it's also true that it doesn't inhibit SIRT.  I'll have to go back over the NR Curated thread to find and create a list of all the relevant studies so give me time on that one.

 

Evolution is highly reproduction dependent. The only advantages are purely related to reproduction success. This is why we continue to age, it's a late acting process. NAD+ doesn't start it's decline until after most people have kids. If people were consistently having kids in their 50's and fewer and fewer people were having them in their 20's, things might change. However, this is not most of human history. You can't say "If evolution had found a benefit for jacking up the NAD+/NADH ratio continuously, it would be naturally higher than it is" because that's just not true. Unless you mean much higher than it is in a person's 20's. Maybe we're talking past each other, but I am not "ill informed" here.

[Nate-2004]

From the OP--

 

Now, I propose that if we were to ask researchers to study any anti-aging combination, it should be Sulforaphane and Nicotinamide Riboside. The combination could potentially produce EXTREMELY synergistic results.

 

 

I think it's likely to be the opposite. NR and other NAD+ precursors get the mitochondrial quality control system running, whereby dysfunctional mitochondria are tagged, engulfed by lysosomes, and digested. To fit them into lysosomes they must be fissioned into the smallest possible size, and then later they fuse together to produce mitochondria that are more robust than before. So anything that prevents fission is going to reduce or eliminate the effectiveness of NR. And sulforaphane is a promoter of "hyperfusion," which means they are even larger than normal. Thus these supplements are working at cross purposes.

 

See this paper--

 

We demonstrate here that SFN [Sulforaphane] induces mitochondrial hyperfusion . . .

https://www.ncbi.nlm...les/PMC5126150/

 

 

 

So unless someone is getting amazing results with this combination (I doubt it), I wouldn't take them at the same time. And I wouldn't take either supplement all the time.

 

Mitochondrial fission isn't the only positive or even primary benefit of NR. Sulforaphane activates a number of pathways, NQ01 (NQO1 stabilizes p53), NrF2, and inhibits phase 1 biotransformation enzymes as well as activating phase 2 detoxification enzymes. There are also other benefits. That the two might cancel out one aspect of benefit from each other doesn't mean they're bad to take together. Even if it reduces the effectiveness of NR in that one area, you still benefit from both. You could see more benefit from alternating days that you take sulforaphane. However, it's not a bad thing to take both. That's just not true.

Edited by Nate-2004, 11 March 2017 - 11:04 PM.

[jjnz]

fwiw Rhonda Patrick no longer heats her sprouts, I'll try to find a reference to this

[Nate-2004]

Really? Would love to know why. I also happen to know that she doesn't grind the seeds either, just eats the sprouts apparently.

[Cube]

https://www.google.c...followup_to_my/

Another interview with jw fahey
Some interesting points most of you have probably seen it. The miracle tree is easy to grow I'd be interested in myrosinase content.