18 replies to this topic

[Addison Strack]

I...

Edited by Addison Strack, 09 August 2007 - 07:53 PM.

[Brainbox]

This is what LEF has to say about cholesterol testing in a broader perspective, but there's no link with NAC preventing the Lp(a).

[shamus]

What's Lp(a)?

[Brainbox]

Lp(a): Lipoprotein(a); an inherited risk factor for heart disease. It is more dangerous than other types of cholesterol, and does not respond to traditional LDL-lowering drugs.

I do not have any knowledge on more detailed biochemical facts.

[zoolander]

I can't see much in support for it except that it prevents apoptosis, is a glutothione precursor, and it is a potent anti-oxidant.

The three benefits that you mention above are all connected to N-A-C ability to act as a good stable and bioavailable form of cysteine. I'm sitting on the other side of the fence to you Addision. I can't see how people do not include this very cheap supplement into their regime. NAC is a staple. An absolute must in my regime.

If I were to explain all the positives I would fill a page. I'll be dedicating a full chapter about the importance of a cysteine rich diet and aging to my thesis.

[woly]

Zoolander, what do you think about the possibility of it having carcinogenic properties too?

Although N-acetylcysteine is an antioxidant which has been expected to be a cancer chemopreventive agent, its safety and risk assessment have not been evaluated. N-acetylcysteine increased the amount of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a characteristic oxidative DNA lesion, in human leukemia cell line HL-60, whereas the amount of 8-oxodG in HP100, which is a hydrogen peroxide (H[2]O[2])-resistant cell line derived from HL-60, was not increased. To clarify the mechanism of cellular DNA damage, we investigated DNA damage and its site specificity induced by N-acetylcysteine, using [32]P-labeled DNA fragments obtained from the human p53 tumor suppressor gene and the c-Ha-ras-1 protooncogene. N-acetylcysteine induced extensive DNA damage in the presence of Cu(II). The DNA cleavage was enhanced by piperidine treatment, suggesting that N-acetylcysteine plus Cu(II) caused not only deoxyribose phosphate backbone breakage but also base modification. N-acetylcysteine plus Cu(II) frequently modified thymine and guanine residues. Bathocuproine, a specific Cu(I) chelator, and catalase inhibited the DNA damage, indicating the participation of Cu(I) and H[2]O[2] in the DNA damage. Typical hydroxyl radical scavengers did not inhibit N-acetylcysteine plus Cu(II)-induced DNA damage, whereas methional completely inhibited it. These results suggest that reactive species derived from the reaction of H[2]O[2] with Cu(I) participates in N-acetylcysteine plus Cu(II)-induced DNA damage. The content of 8-oxodG in calf thymus DNA was increased by N-acetylcysteine in the presence of Cu(II). The present study has demonstrated that N-acetylcysteine could induce metal-dependent H[2]O[2] generation and, subsequently, damage to cellular and isolated DNA. Therefore, it is reasonable to consider that N-acetylcysteine may have the dual function of carcinogenic and anti-carcinogenic potentials. This work requires further studies on safety and risk assessment of N-acetylcysteine.

link

[luv2increase]

Very frightening. So, this is only in leukemia cells, right? That is what I got out of it. If so, this study isn't very relevant because a leukemia cell functions vastly different than the normal, average cell.

What are your thoughts on this Zoo? I agree about NAC being a staple in everyone's regimen. I take about a gram daily, 500mg in morning and 500mg at night.

[Shepard]

Have you guys read the full text for that yet?

http://carcin.oxford.../full/20/8/1485

[wydell]

Have you guys read the full text for that yet?

http://carcin.oxford.../full/20/8/1485

The following statement from the above article has me wondering whether I should readjust the lintake evels of some of my supplements:

"There is growing evidence that compounds that are antioxidants at some concentrations become prooxidants at other concentrations"

Sometimes less is more I suppose. I wonder which "compounds" they have evidence of having this effect.

[inawe]

Atherosclerosis. 1996 Jan 5;119(1):99-106.
N-acetylcysteine treatment lowers plasma homocysteine but not serum lipoprotein(a) levels.
Wiklund O, Fager G, Andersson A, Lundstam U, Masson P, Hultberg B.
Wallenberg Laboratory, Sahlgren's Hospital, Göteborg, Sweden.

High levels of lipoprotein(a) (Lp(a)) or homocysteine in plasma have both been associated with an increased risk for premature cardiovascular disease. For both components, the plasma levels are primarily genetically determined, and they have been very restintant to therapeutic approaches. It has been suggested that N-acetylcysteine (NAC) breaks disulphide bonds in Lp(a) as well as between homocysteine and plasma proteins. In the present study we analyze if this mechanism, in vivo, could be used to lower plasma concentrations of Lp(a) and homocysteine. Treatment with NAC and placebo was performed in a double blind cross over design with 2 weeks wash-out between treatments. Eleven subjects with high plasma Lp(a) (> 0.3 milligram) were recruited from the Lipid Clinic at Sahlgren's Hospital, Göteborg, Sweden. Main outcome measures were treatment effects on plasma Lp(a) and plasma amino thiols (homocysteine, cysteine and cysteinyl glycine). There was no significant effect on plasma Lp(a) levels. Plasma thiols were significantly reduced during treatment with NAC: homocysteine by 45% (P < 0.0001), cysteinyl glycine by 24% (P < 0.0001) and cysteine by 11% (P = 0.0002). The high dose of NAC was well tolerated. In conclusion NAC has no effect on plasma Lp(a) levels while the reduction in homocysteine is considerable and might be of clinical significance in cases with high plasma homocysteine levels.

PMID: 8929261 [PubMed - indexed for MEDLINE]

[Shepard]

1: J Intern Med. 1991 Dec;230(6):519-26.Links
N-acetylcysteine and serum concentrations of lipoprotein(a).
Kroon AA, Demacker PN, Stalenhoef AF.

Department of Medicine, University Hospital Nijmegen, The Netherlands.

A high plasma concentration of lipoprotein(a) [Lp(a)], a complex of low-density lipoprotein linked by disulphide bridges to apoprotein(a), is correlated with premature atherosclerosis. We determined whether the serum Lp(a) concentration could be decreased in vitro and in vivo by the reducing agent N-acetylcysteine (NAC), a drug used as a mucolytic agent, which acts by cleaving disulphide bonds. High concentrations of NAC (greater than or equal to 8 mg ml-1) resulted in dissociation of the Lp(a) antigen in vitro. However, the plasma level of Lp(a) was not changed by administration of NAC 1.2 g d-1 for 4 weeks in 7 subjects with a median Lp(a) concentration of 14.3 mg dl-1 (range 2.1-21.0 mg dl-1) or by doubling the dose to 2.4 g d-1 for a further 2 weeks. In 12 subjects with a high plasma level of Lp(a), median 87.0 mg dl-1 (range 42.0-201.6 mg dl-1), a small but significant decrease in Lp(a) concentration of 7% (P = 0.02) was observed after administration of NAC in a dose of 1.2 g d-1 for 6 weeks. These results indicate that NAC has only a limited capacity to reduce the concentration of Lp(a), which is not clinically significant.

PMID: 1836221 [PubMed - indexed for MEDLINE]

[inawe]

There is a group in Spain quite active in the study of the effects of Lp(a).
As of November 2004 their view was (and I'm translating from Spanish):
"There is no effective treatment for hyper-Lp(a)".

[Brainbox]

Sometimes less is more I suppose.  I wonder which "compounds"  they have evidence of having this effect.

N-acetylcysteine concentrations tested in this study can be considered high relative to concentrations likely to result from the use of the compound in chemoprevention trials to humans (600 mg/daily). However, the concentration of N-acetylcysteine (1 mM) causing oxidative DNA lesion is lower than the concentration (10 mM) which is reported to protect against oxidative stress in the cells (8) and may be considered roughly comparable with the concentrations showing the chemopreventive effect of N-acetylcysteine in animals (1–2 g/kg body weight)

It seems to be the other way round. Strange is that (if I read it correctly) that the oxidative effect occurs at the concentration in which at the same time chemo-preventive effect is shown. I guess this is because different type of cell's are involved in both situations?
Furthermore they seem to compare the result from different studies that could have been carried out in incomparable in vitro conditions?
Does anyone understand what the Cu concentrations have been in this study, was this according to normal situations?

[Brainbox]

Bump

[woly]

isnt the amount of cysteine in whey enough?

my protein powder contains 1.7g of cysteine per 100g. now i take 30grams per scoop. so isnt that roughly 550mg of cysteine which is around the standard dose of NAC?

[luv2increase]

L-Cysteine is not the same as N-acetyl-cysteine. The latter is better.

[ortcloud]

It doesn't respond to drugs, it only responds modestly to lifestyle changes such as diet and exercise, and is largely thought to be an inherited factor. There's no method I know of to control or lower it.

[ortcloud]

Maybe it is more accurate to say "there is not a drug that drs. can prescribe to lower it."


linus pauling discovered decades ago that simple vitamin c lowers it. Check out pauling therapy.

The link here might be glutathione, since vitamin c and NAC both raise glutathione levels. Or another theory is the spackle repair theory. Lpa is very sticky which is why it is so dangerous. But it only seems to appear when you have low vitamin c levels. Vitamin c is needed for collagen production and your arteries need collagen to repair themselves, so some have speculated that lpa is a response to a vitamin c deficiency which causes cracks in the arteries and the lpa is used to fill in the cracks and substitute for collagen.

[ageless]

Maybe it is more accurate to say "there is not a drug that drs. can prescribe to lower it."


linus pauling discovered decades ago that simple vitamin c lowers it. Check out pauling therapy.

The link here might be glutathione, since vitamin c and NAC both raise glutathione levels. Or another theory is the spackle repair theory.  Lpa is very sticky which is why it is so dangerous. But it only seems to appear when you have low vitamin c levels. Vitamin c is needed for collagen production and your arteries need collagen to repair themselves, so some have speculated that lpa is a response to a vitamin c deficiency which causes cracks in the arteries and the lpa is used to fill in the cracks and substitute for collagen.

This might be what you're looking for:
http://www.aor.ca/int/products/tlc.php
http://www.aor.ca/in...esearch/tlc.php