48 replies to this topic

[rongqiaohe]

We must pay attention to the problems resulted from taking D-ribose. Please a recent paper by my group.
http://www.pibb.ac.c...20130341&flag=1

[hav]

What are the pulmonary or other issues regarding NAC?

I've been taking 600mg/day of time released NAC a day because of a recent study which indicated that it helps curtail damage caused by long term antibiotic use. What other problems could I be causing for myself by taking the NAC?

So does cellgevity bypass the concerns that N.A.C has regarding pulmonary issues? Also came across this thread (of course after I ordered some) http://scam.com/show...d.php?p=1181842

Here's the 2007 mouse study that showed an increase in pulmonary arterial hypertension after feeding mice 10/mg per ml of NAC in their drinking water:
http://www.ncbi.nlm....pubmed/17786245

But probably more relevant is an older 2002 study in humans that found an increase in hypoxic ventilatory response at a NAC dosage level of 600 mg taken 3x a day.

I think both of these studies are measuring the same effect: an increase in localized pressure specific to a vessel carrying deoxygenated blood. The 2007 study found the effect only showed up at NAC dosage levels sufficient to cause an excess formation of S-nitroso-N-acetylcysteine (SNOAC) as a NAC metabolite. Which they found at 10mg/ml but not at 1 mg/ml in mice. Eyeballing the charts the effect in humans looks like only about a 25% increase compared to what looks like about a 66% increase in mice at the dosages tested and seems to persist about 3 weeks.

I have no idea is the ribocene combo might result in SNOAC metabolites. But some of the ingredients seem to be there.

Howard

[GetMaxed]

We must pay attention to the problems resulted from taking D-ribose. Please a recent paper by my group.
http://www.pibb.ac.c...20130341&flag=1

Hi rongqiaohe,

I did notice the glycating properties of Ribose when I first looked at RiboCeine. However it is also a essential building block of ATP and RNA. Like many nutrients there is a U shaped dose-response curve. Too little is a problem, as it too much. The same can be said with supplements for other nutrients required for glutathione synthesis and function, such as L-Cysteine and Selenium.

Supplementing with Ribose has also been shown to have beneficial results, see http://www.lef.org/m...our-Life_01.htm
The doses in the patient groups ranged from 5g/day to 30g/day, which is significantly more than the 250mg of RiboCeine in the recommended daily dose.

Diabetics have low levels of glutathione which increases the the formation of glycation products.

For anyone interested in Glutathione, Redox homeostasis and Cysteine in the aging process, I've just posted up the first cut of my 5,000 word Part 1 epic on the topic at http://danielcampagn...-gsh-cysteine-1

[GetMaxed]

FYI I have just posted up my 2nd article Factors Affecting Redox, GSH Levels and Function (the follow up to The Master Regulator of Aging? - Redox, Glutatione and Cysteine, Part 1)

[Logic]

GetMaxed

Shot for an interesting read.

The fact that James Watson and Vince Guiliano have decided that you should win the the princely sum of 2$ and coveted 'Most Important cellular adaptive mechanism in aging' prise says a lot!

Its kinda peer reviewed now IMHO!
Well won!

"...I am not the Nobel Laureatte (James D Watson) who unraveled the 3D structure of DNA, but I am the one who made the two $1 wagers with Vince Guiliano regarding what signaling pathway is the most important one in aging. As part of the prestigious committee who awards these two very high priced wagers, I am concerned that I have “lost the wager”. It is not even the end of 2013 and you have “outdone both Dr. Vince Guiliano and Dr. Watson. Your two blogs regarding Redox, Glutathion, and Cysteine were fabulous and should be applauded as outstanding blog journalism..."
http://danielcampagn...-gsh-cysteine-1
http://danielcampagn...-gsh-cysteine-2
http://danielcampagn...-gsh-cysteine-3

I think a closer look at the role ribose plays is worth a closer look.

Ribose looks to be involved in the intracellular salvage of Nicotinamide and may lower its levels by helping in its salvage back into NAD+ - ATP and thus unlocking SIRT etc. potential and all that is downstream...
http://www.longecity...-strikes-again/
http://www.longecity...-thread/page-12

I have a pet theory that Nicotinamede Ribocide is mostly, likely slow release Nicotinamide and ribose, based on the only study looking at NR in the gut which did not find any NR making it through the intestinal lining?
http://www.longecity...ndpost&p=690504


Do you have any info how RiboCeine is digested etc?

Edited by Logic, 06 October 2014 - 09:58 PM.

[GetMaxed]

GetMaxed

Shot for an interesting read

The fact that James Watson and Vince Guiliano have decided that you should win the the princely sum of 2$ and coveted 'Most Important cellular adaptive mechanism in aging' prise says a lot!

Its kinda peer reviewed now IMHO!
Well won!

Thanks! I hadn't thought of it like that before haha
 

Do you have any info how RiboCeine is digested etc?

 
There is a link on the page here with all the RiboCeine studies. There is one on bio distribution of glutathione elevation
Time course for the elevation of glutathione in numerous organs of L1210-bearing CDF1 mice given the l-cysteine prodrug, RibCys 
 

 GSH content was assayed 1, 2, 4, 8 and 16 h after RibCys administration[/size]; various organs achieved maximal GSH content at different time points. GSH in the liver was elevated 1.5-fold compared to untreated controls at the 16-h time point. Kidney GSH also was maximal at 16 h and achieved 1.6-times control values. GSH in muscle achieved 2.5 times the levels in control animals, while the bladder was elevated 2.1-fold, and the heart 1.8-fold.[/size]

 
I've heard it said about RibCys that it absorbs through the digestive track and into the cells, and that it is "release-on-demand" which the above data would support with maximal levels after 16hrs, so you're getting the slow release if required.  The toxicity studies with acetaminophen poisoning shows it is effective in shorter time frames. The molecule separates by non-enzymatic ring opening and hydrolysis.
 
I had thought the Ribose component was underrated for it's direct benefits such as replenishing ATP levels, and not just protecting the cysteine.  There some good bits to read in the patent about the Ribose side of it.

 

Have a read through this other post on my blog, some interesting things I was learning about GSH, NAD, NAPDH, AMPK and redox regulation.

 

I had a read through the threads on the NR. Will be interested to see where that develops. I'm interested in NAD+ and NR too as NAD/NADH and NADP/NADPH along with GSH/GSSG make the main redox couples.

[ta5]

New study showed up today:

 

 

Atherosclerosis. 2014 Nov 1;237(2):725-733.

Ribose-cysteine increases glutathione-based antioxidant status and reduces LDL in human lipoprotein(a) mice.

Kader T1, Porteous CM1, Williams MJ2, Gieseg SP3, McCormick SP4.

Department of Biochemistry, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.

Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.

School of Biological Sciences, University of Canterbury, Christchurch, New Zealand.

Objective: 

d-ribose-l-cysteine (ribose-cysteine) is a cysteine analogue designed to increase the synthesis of glutathione (GSH). GSH is a cofactor for glutathione peroxidase (GPx), the redox enzyme that catalyses the reduction of lipid peroxides. A low GPx activity and increased oxidised lipids are associated with the development of cardiovascular disease (CVD). Here we aimed to investigate the effect of ribose-cysteine supplementation on GSH, GPx, lipid oxidation products and plasma lipids in vivo.

Methods:

Human lipoprotein(a) [Lp(a)] transgenic mice were treated with 4 mg/day ribose-cysteine (0.16 g/kg body weight) for 8 weeks. Livers and blood were harvested from treated and untreated controls (n = 9 per group) and GSH concentrations, GPx activity, thiobarbituric acid reactive substances (TBARS), 8-isoprostanes and plasma lipid concentrations were measured.

Results:

Ribose-cysteine increased GSH concentrations in the liver and plasma (P < 0.05). GPx activity was increased in both liver (1.7 fold, P < 0.01) and erythrocytes (3.5 fold, P < 0.05). TBARS concentrations in the liver, plasma and aortae were significantly reduced with ribose-cysteine (P < 0.01, P < 0.0005 and P < 0.01, respectively) as were the concentrations of 8-isoprostanes in the liver and aortae (P < 0.0005, P < 0.01, respectively). Ribose-cysteine treated mice showed significant decreases in LDL, Lp(a) and apoB concentrations (P < 0.05, P < 0.01 and P < 0.05, respectively), an effect which was associated with upregulation of the LDL receptor (LDLR).

Conclusions:

As ribose-cysteine lowers LDL, Lp(a) and oxidised lipid concentrations, it might be an ideal intervention to increase protection against the development of atherosclerosis.

PMID: 25463112

[ironfistx]

Some people use NAC for treatment of ringing in the ears and it is supposed to prevent hearing damage if taken before and after exposure to noise.  Could Riboceine have this same effect since the concept is that glutathione is depleted by loud noises and replenish the supply will allow your body to reduce ear damage?

[caruga]

Just remember if you raise GSH you'll want to take b-vitamins and selenium to recycle GSSG.

[GetMaxed]

 

New study showed up today:

 

 

Atherosclerosis. 2014 Nov 1;237(2):725-733.

Ribose-cysteine increases glutathione-based antioxidant status and reduces LDL in human lipoprotein(a) mice.

Kader T1, Porteous CM1, Williams MJ2, Gieseg SP3, McCormick SP4.

Department of Biochemistry, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.

Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.

School of Biological Sciences, University of Canterbury, Christchurch, New Zealand.

Objective: 

d-ribose-l-cysteine (ribose-cysteine) is a cysteine analogue designed to increase the synthesis of glutathione (GSH). GSH is a cofactor for glutathione peroxidase (GPx), the redox enzyme that catalyses the reduction of lipid peroxides. A low GPx activity and increased oxidised lipids are associated with the development of cardiovascular disease (CVD). Here we aimed to investigate the effect of ribose-cysteine supplementation on GSH, GPx, lipid oxidation products and plasma lipids in vivo.

Methods:

Human lipoprotein(a) [Lp(a)] transgenic mice were treated with 4 mg/day ribose-cysteine (0.16 g/kg body weight) for 8 weeks. Livers and blood were harvested from treated and untreated controls (n = 9 per group) and GSH concentrations, GPx activity, thiobarbituric acid reactive substances (TBARS), 8-isoprostanes and plasma lipid concentrations were measured.

Results:

Ribose-cysteine increased GSH concentrations in the liver and plasma (P < 0.05). GPx activity was increased in both liver (1.7 fold, P < 0.01) and erythrocytes (3.5 fold, P < 0.05). TBARS concentrations in the liver, plasma and aortae were significantly reduced with ribose-cysteine (P < 0.01, P < 0.0005 and P < 0.01, respectively) as were the concentrations of 8-isoprostanes in the liver and aortae (P < 0.0005, P < 0.01, respectively). Ribose-cysteine treated mice showed significant decreases in LDL, Lp(a) and apoB concentrations (P < 0.05, P < 0.01 and P < 0.05, respectively), an effect which was associated with upregulation of the LDL receptor (LDLR).

Conclusions:

As ribose-cysteine lowers LDL, Lp(a) and oxidised lipid concentrations, it might be an ideal intervention to increase protection against the development of atherosclerosis.

PMID: 25463112

 

 

Good find! And seems like good results. The dosage is fairly close to whats in the product Ribose-Cystine is in I take, which has 250mg/day ~ 3.6mg/day for a 70kg person.  The study used 4 mg/day ribose-cysteine (0.16 g/kg body weight) 

 

ironfistx, Riboceine would most likely have the same effect on the ears.  Ribose-Cysteine works by providing cysteine for GSH synthesis, and studies have shown it to have better bio-availability than NAC

[Inka]

A 51-year-old man from Puerto Rico with Child-Turcotte-Pugh Class C decompensated cirrhosis due to genotype 1a chronic hepatitis C was referred for worsening jaundice and diuretic-resistant ascites. He began experiencing symptoms of hepatic decompensation 5 months prior to referral with new-onset ascites and spontaneous bacterial peritonitis, evolving into diuretic-resistant ascites, increasing jaundice, and a MELD increase from 12 to 29. During his hospitalization, his MELD score increased to >40 from a rapidly increasing international normalized ratio (INR) and evolving type 1 hepatorenal syndrome. Clinically, the patient appeared quite well despite such a high MELD score. After an extensive pretransplant evaluation and exclusion of infection, he underwent successful orthotopic liver transplantation. After histologic examination of the explanted liver, he subsequently admitted to 5 months of daily use of a detoxifying supplement known as MaxOne (®), containing D-ribose- L-cysteine, consistent with a drug-induced acute-on-chronic liver failure. The use of complementary and alternative medicines and its potential for causing drug-induced liver injury and acute-on chronic liver failure requires a high index of suspicion and increased awareness among health care providers.

 

Is this something to worry about? I just got 2 months supply and now hesitant to take it.

[Captain Obvious]

Bump. Is anyone still taking a ribose-cysteine product?

I wonder why this combination might lead to liver cirrhosis. Does the liver have to work too hard to synthesize glutathione when stimulated with ribose-cysteine, or what could be the cause?

[GetMaxed]

I'm still taking it regularly, and up the dose when I'm enjoying a few drinks.  Note that person had chronic hepatitis C and already a sick liver.  I do remember when researching the topic that when the liver is in the final stages of diseases that treatments/supplements that might otherwise benefit can have a detrimental effect as its past the stage of being able to properly process them and benefits from hormetic effects. For a health person its really not an issue. The compound was developed by a highly regarded medicinal chemist to prevent cirrhosis from happening in the first place.

[Logic]

I'm still taking it regularly, and up the dose when I'm enjoying a few drinks.  Note that person had chronic hepatitis C and already a sick liver.  I do remember when researching the topic that when the liver is in the final stages of diseases that treatments/supplements that might otherwise benefit can have a detrimental effect as its past the stage of being able to properly process them and benefits from hormetic effects. For a health person its really not an issue. The compound was developed by a highly regarded medicinal chemist to prevent cirrhosis from happening in the first place.

 

Ah GetMaxed; our 'peer reviewed' Riboceine pusher!  

I'm glad to see you're still around!

• How long have you been taking Riboceine?
• What effects have you experienced subjectively?
• Have you had any blood tests etc done that show an improvement in health markers?
• How is your liver!?
• Where do you/is the best place to get Riboceine?

I ask as I am very interested in Riboceine as a form of slow release D-Ribose GetMaxed.
I think that it, combined with a slow release form of Niacin/nicotinic acid, may give better results than Nicotinamide Riboside for boosting NAD+.

You mentioned its slow intracellular release of Ribose?  Any proof/studies?

Inositol Hexanicotinate is a good form of slow release Niacin, but ​Inositol blocks the very necessary autophagy that occurs at night/during the fasted state.
Chromium (Poly/Hexa) Nicotinate looks like a better choice later in the day.

 

'Don't try this at home kids!'

Especially with plain D-Ribose:

Ribose and Niacin are turbo boosters of nasty gut bacteria like Candida!!!
Ribose is a potent AGE former!

 

Pterostilbene is an anti biofilm supp besides being a SIRT booster, if you do try, and is in good NR supps for both reasons IMHO.

VCO is also anti Candida and many other nasty pathogens. 

Edited by Logic, 09 June 2016 - 02:54 AM.

[gamesguru]

• Onion extract (kaempferol, apigenin, quercetin) was able to increase the intracellular concentration of glutathione by approximately 50%.
• galangin increases levels 123% [1]
• silymarin by 125-150%
• blueberries by 130% [2]

1.5 * 1.5 *1.23 * 1.25 * 1.3 = 4.5 > 3.0

also i think exercise has a small effect

[Harkijn]

 

I'm still taking it regularly, and up the dose when I'm enjoying a few drinks.  Note that person had chronic hepatitis C and already a sick liver.  I do remember when researching the topic that when the liver is in the final stages of diseases that treatments/supplements that might otherwise benefit can have a detrimental effect as its past the stage of being able to properly process them and benefits from hormetic effects. For a health person its really not an issue. The compound was developed by a highly regarded medicinal chemist to prevent cirrhosis from happening in the first place.

 

Ah GetMaxed; our 'peer reviewed' Riboceine pusher!  

I'm glad to see you're still around!

• How long have you been taking Riboceine?
• What effects have you experienced subjectively?
• Have you had any blood tests etc done that show an improvement in health markers?
• How is your liver!?
• Where do you/is the best place to get Riboceine?

I ask as I am very interested in Riboceine as a form of slow release D-Ribose GetMaxed.
I think that it, combined with a slow release form of Niacin/nicotinic acid, may give better results than Nicotinamide Riboside for boosting NAD+.

You mentioned its slow intracellular release of Ribose?  Any proof/studies?

Inositol Hexanicotinate is a good form of slow release Niacin, but ​Inositol blocks the very necessary autophagy that occurs at night/during the fasted state.
Chromium (Poly/Hexa) Nicotinate looks like a better choice later in the day.

 

'Don't try this at home kids!'

Especially with plain D-Ribose:

Ribose and Niacin are turbo boosters of nasty gut bacteria like Candida!!!
Ribose is a potent AGE former!

 

Pterostilbene is an anti biofilm supp besides being a SIRT booster, if you do try, and is in good NR supps for both reasons IMHO.

VCO is also anti Candida and many other nasty pathogens. 

 

Logic if I read you right you see a Candida risk for NR use. That's a serious drawback. Did you post about it in another thread? I don't think I read about it in the NR(Curated) thread... Have you got a source so I can dig a little deeper? Thanks!

[GetMaxed]

Hi Logic! haha yes I still get an email when there's a new post, its been a while since I've had a browse of pubmed so its nice to think about it again.

 

This was one of the articles that indicated a slow release with maximal GSH 16 hours after.

http://www.sciencedi...37842749190078K

 

 

GSH content was assayed 1, 2, 4, 8 and 16 h after RibCys administration (8 mmolkg, i.p.); various organs achieved maximal GSH content at different time points. GSH in the liver was elevated 1.5-fold compared to untreated controls at the 16-h time point. Kidney GSH also was maximal at 16 h and achieved 1.6-times control values.

This NASA sponsored study hints at a prophylactic usage from pre-loading hours before the radiation dosage, 

 

 

These results, together with the minimal side effects reported in mice and pigs, indicate that RibCys may be useful, perhaps even when used prophylactically, in reducing the load of mutations created by high LET radiation in astronauts or other exposed individuals. RibCys is an attractive drug that may reduce the risk of carcinogenesis in people exposed to high LET radiation.

 

• How long have you been taking Riboceine? 
• What effects have you experienced subjectively? 

A few years now, in the Cellgevity formulation. Before that I took the NAC formulation. I remember when I first took that noticeably needing less sleep and waking up feeling more refreshed, and recovering a bit quicker from hard exercise. 

• Have you had any blood tests etc done that show an improvement in health markers?  
• I haven't done any blood tests myself. I'm pretty healthy and not too old, 35, so only a smaller room for improvement. Its the more unwell people I've heard from that have the more impressive improvements. I got the email recently from someone I sent a weeks supply to.

•  

  I've been super impressed with the Cellgevity / Riboceine. My strength and endurance is increasing noticeably and I'm handling my other treatments (immune system treatments for chronic fatigue syndrome) with greater ease. 

   

  Currently I'm only taking 1 cap/day [1/4 dose], I hope to increase that over time. So a 1-month supply will last me longer than 1 month.  

   

•  
• How is your liver!? 
• It seems pretty good! I can knock back a few drinks without any ill effects the next day, I try not to do that as often these days :p
•  
• Where do you/is the best place to get Riboceine?
• You should only get it (maxone and cellgevity are the product names) through the max.com website (a referral link/id is required)

Ribose is a potent AGE former!

Oxidative stress causes AGE's too, don't breathe too much Ribose is a building block of RNA. Just like oxygen can't live forever with it, can't live without it!

 

 

 

I think that it, combined with a slow release form of Niacin/nicotinic acid, may give better results than Nicotinamide Riboside for boosting NAD+.

I was interested in this link too, and also any interplay between GSH/GSSG and NADH/NAD+, but I scratched my intellectual itch a while ago and haven't done any bio-chem research for a while.

 

 

A couple of new journal articles since then:

d-ribose-l-cysteine supplementation enhances wound healing in a rodent model

Ribose-cysteine increases glutathione-based antioxidant status and reduces LDL in human lipoprotein(a) mice.

Edited by GetMaxed, 27 June 2016 - 05:13 PM.

[Matt79]

Getmaxed- thanks for your participation and sharing your knowledge.

 

I am curious though if anyone else, besides getmaxed, has taken ribcys? I find the story kind of interesting

 

With that said

1. Much of the information online has a bit of a spammy nature to it focusing on RiboCeine ™ and also seemingly non-independent.
2. hepatoxicity / safety issue. I want to see liver panels from frequent users

 

Edited by Matt79, 02 April 2017 - 04:59 PM.

[RWhigham]

I checked a couple of the mouse studies for Riboceine dosing. One example gave a daily dose of 4 mg per 25 g mouse.

 

Human Equivalent Dose for a 70 kg man is (70000 g/25 g)(4 mg/12) = 933 mg daily  (with a HED mouse correction factor of 1/12)

 

933 mg of Riboceine at 125 mg/capsule takes 933/125 = 7.46 capsules. This costs about $140/120 capsules x 7.46 capsules = $8.70 per day

 

Comparison with NAC

One study found 2.5 mmol concentration of NAC to be comparable to 1 mmol concentration of Riboceine. 

 

Molar Masses

Riboceine ref  2(R,S)-D-ribo-(1′,2′,3′,4′-tetrahydroxybutyl)thiazolidine-4®-carboxylic acid has a molar mass of 253.28 ref 

N-acetyl cysteine has a molar mass of 163.19 mg/mmol

 

Riboceine dose in mmol

The riboceine dose is (933 mg)/(253 mg/mmol) = 3.69 mmol.

 

NAC dose giving 2.5 higher mmol concentration

     (2.5)(3.69 mmol) = 9.22 mmol

 

Nac dose in mg

(9.22 mmol)(163.19 mg/mmol) = 1.5 g = three 500mg capsules. Jarrow 500 mg costs about 8.5 cents per capsule for a cost of 25 cents per day

 

Caveat: I will not take more than 500 mg per day of NAC.   I would much prefer the Riboceine except for its cost. 

 

Edited by RWhigham, 28 October 2017 - 11:22 PM.