3 replies to this topic

[Advanc3d]

i was reading somewhere that high dose of the amino acid l-cysteine will cause oxidative stress and dna damage
whats the deal with this? and how much is a high dose

i take this formula capsule daily for hair health
1200mg cysteine
300mg vitamin c
25mg vitamin b6

would that be a high dose, could it be causing toxic effects?

[Mixter]

I think it may depend on the supplement quality. If the cysteine is in an oxidized state, with disulfide bonds formed, it's probably a harmful oxidant.

600mg N-Acetyl-L-cysteine per day (for other reasons) is reasonably safe if taken with a lot of water,
it's a common way to boost gluthatione and also provides cysteine. IIRC some study indicates that
even excessive NAC may be a risk factor for hypertension, though...

For hair health and structure, rather try a silicate supplement... usually it's
not a lack of sulfur/cysteine, plus maybe try a shampoo with PEG + caffeine.

To really supplement with a lot of sulfur in a safe way, if needed, the best way
may be (good-quality) methyl-sulfonyl-methane (MSM) for a limited time, which is for
example used for joint and connective tissue problems.

[Wulf]

Where did you read this and which study was referenced?

A few papers I found were:

L-cysteine-induced brain damage in adult rats.
Sawamoto O, Hagiwara R, Kurisu K. Drug Safety and Metabolism, Otsuka Pharmaceutical Factory Inc, Muya-cho, Naruto, Tokushima 772-8601, Japan. sawamoos@otsukakj.co.jp

The time-dependent brain damage induced in adult rats by a single dose of L-cysteine was examined morphologically. Five-week-old male Sprague-Dawley rats that received 1500 mg/kg of L-cysteine by intraperitoneal injection were examined at 12 and 24 h and 3, 7, and 14 days after administration. Pathological changes were seen in the cerebral and cerebellar cortex. Neuronal karyopyknosis was observed in the granular and molecular layers of the superficial cerebellar cortex at 12 h, and well-demarcated infarct-like lesions were seen with a widespread distribution in the cerebral cortex at 24 h. A large number of lipid phagocytes and glial cell proliferation were noted in the affected regions on days 3 to 14. The neuronal cell death observed in the cerebellar granular layer cells was demonstrated to be due to apoptosis by histopathological and ultrastructural examinations as well as by the terminal deoxyribonucleotide transferase-mediated dUTP nick-end labeling (TUNEL) method and agarose gel electrophoresis for DNA laddering. It was found that L-cysteine induced brain lesions mainly in the cerebral and cerebellar cortex in adult rats, in contrast to lesions in various regions as observed in neonatal rats. The histopathological findings reported here suggest that the pathogenesis of the brain damage induced by L-cysteine in adult rats differs from that in neonatal rats. It appears likely that L-cysteine-induced brain damage is secondary to impairment of blood flow or other unknown factors that are responsible for the subsequent development of brain lesions.

PMID: 15581274 [PubMed - indexed for MEDLINE]

The HED used in the aforementioned study works out to be 17027 mg in a 70kg human.

Mechanisms of L-Cysteine Neurotoxicity

Abstract We review here the possible mechanisms of neuronal degeneration caused by L-cysteine, an odd excitotoxin. L-Cysteine lacks the omega carboxyl group required for excitotoxic actions via excitatory amino acid receptors, yet it evokes N-methyl-D-aspartate (NMDA) -like excitotoxic neuronal death and potentiates the Ca²⁺ influx evoked by NMDA. Both actions are prevented by NMDA antagonists. One target for cysteine effects is thus the NMDA receptor. The following mechanisms are discussed now: (1) possible increase in extracellular glutamate via release or inhibition of uptake/degradation, (2) generation of cysteine -carbamate, a toxic analog of NMDA, (3) generation of toxic oxidized cysteine derivatives, (4) chelation of Zn²⁺ which blocks the NMDA receptor-ionophore, (5) direct interaction with the NMDA receptor redox site(s), (6) generation of free radicals, and (7) formation of S-nitrosocysteine. In addition to these, we describe another new alternative for cytotoxicity: (8) generation of the neurotoxic catecholamine derivative, 5-S-cysteinyl-3,4-dihydroxyphenylacetate (cysdopac).

http://www.springerl...13384gu6110614/

Most of the the other studies I found relate to NAC and its prevention of oxidative damage, such as this:

Effect of N-acetyl cysteine on oxidative DNA damage and the frequency of DNA deletions in atm-deficient mice.
Reliene R, Fischer E, Schiestl RH. Department of Pathology, Geffen School of Medicine and School of Public Health, University of California-Los Angeles, 650 Charles E. Young Drive South, Los Angeles, CA 90024, USA.

Ataxia telangiectasia (AT) is a hereditary human disorder resulting in a wide variety of clinical manifestations, including progressive neurodegeneration, immunodeficiency, and high incidence of lymphoid tumors. Cells from patients with AT show genetic instability, hypersensitivity to radiation, and a continuous state of oxidative stress. Oxidative stress and genetic instability, including DNA deletions, are involved in carcinogenesis. We examined the effect of dietary supplementation with the thiol-containing antioxidant N-acetyl-l-cysteine (NAC) on levels of oxidative DNA damage and the frequency of DNA deletions in Atm-deficient (AT-mutated) mice. We confirmed that Atm-deficient mice display an increased frequency of DNA deletions (Bishop et al., Cancer Res 2000;60:395). Furthermore, we found that Atm-deficient mice have significantly increased levels of 8-OH deoxyguanosine, an indication of oxidative DNA damage. Dietary supplementation with NAC significantly reduced 8-OH deoxyguanosine level and the frequency of DNA deletions in Atm-deficient mice. These levels were similar to the levels in wild-type mice. Our findings demonstrate that NAC counteracts genetic instability and suggest that genetic instability may be a consequence of oxidative stress in Atm-deficient mice.

PMID: 15289318 [PubMed - indexed for MEDLINE]

Edited by Wulf, 30 June 2008 - 01:43 PM.

[krillin]

http://www.thorne.co...glutathione.pdf

But cysteine is probably unsafe for routine oral administration. When circulating in the blood it readily auto-oxidizes to potentially toxic degradation products. Saez and collaborators demonstrated that the highly reactive hydroxyl radical is among the products formed from the auto-oxidation of cysteine.(94) Cysteine also has “excitotoxin” activity in the brain, similar to that of the amino acids glutamate and aspartate, and can be toxic to the retina. GSH has none of these liabilities, and the GSH redox system may have evolved to supplant the relatively fallible, cysteine-based system.

Teratology. 1988 Aug;38(2):145-55.
Distribution of mercury 203 in pregnant rats and their fetuses following systemic infusions with thiol-containing amino acids and glutathione during late gestation.
Aschner M, Clarkson TW.
Division of Toxicology, School of Medicine and Dentistry, University of Rochester, New York 14642.

To investigate the effect of amino acids and the tripeptide glutathione (GSH) on tissue uptake of methylmercury (MeHg) in the developing rat fetus in utero, pregnant rats were continuously infused into the external jugular vein with 0.1 mM L-cysteine, 0.1 mM L-leucine, 0.1 mM GSH or saline commencing on day 17 of gestation. This was followed at 24, 48, and 72 hours by external jugular infusion of 50 microM [203Hg]-MeHgCl administered in 1 ml over 1 hour. Pups were surgically removed from the uterus on gestational day 21. Whole body, brain, kidney, liver, and placental 203Hg radioactivity was measured by means of gamma-spectrometry. Brain 203Hg concentration in pups exposed in utero to L-cysteine was significantly higher compared with pups exposed to saline (P less than 0.05). Brain 203Hg concentration in pups exposed in utero to L-leucine and GSH was significantly depressed compared with pups exposed to saline (P less than 0.05). Kidney 203Hg concentration was not significantly changed in all treatment groups compared with controls. Liver 203Hg concentration was significantly depressed in L-leucine- and GSH-treated pups compared with controls (P less than 0.05). Placental 203Hg concentration was not affected by any treatment compared with controls. These effects occurred despite no difference in total 203Hg body burden among pups, irrespective of the treatment. In addition, infusion with L-cysteine resulted in a significant increase in 203Hg brain concentration in dams compared with controls, and 203Hg brain concentration in L-leucine- and GSH-treated dams was significantly depressed compared with controls. Thus 203Hg distribution in both adult and developing animals is altered by chronic amino acid or GSH infusions and suggests that MeHg uptake may be mediated through the formation of a cysteine-MeHg complex which is transported across the blood-brain barrier by the neutral amino acid carrier transport system.

PMID: 3175948

Biochem J. 2002 Oct 1;367(Pt 1):239-46.
Transport of a neurotoxicant by molecular mimicry: the methylmercury-L-cysteine complex is a substrate for human L-type large neutral amino acid transporter (LAT) 1 and LAT2.
Simmons-Willis TA, Koh AS, Clarkson TW, Ballatori N.
Department of Environmental Medicine, University of Rochester School of Medicine, 575 Elmwood Avenue, Box EHSC, Rochester, NY 14642, U.S.A.

Methylmercury (MeHg) readily crosses cell membrane barriers to reach its target tissue, the brain. Although it is generally assumed that this rapid transport is due to simple diffusion, recent studies have demonstrated that MeHg is transported as a hydrophilic complex, and possibly as an L-cysteine complex on the ubiquitous L-type large neutral amino acid transporters (LATs). To test this hypothesis, studies were carried out in Xenopus laevis oocytes expressing two of the major L-type carriers in humans, LAT1-4F2 heavy chain (4F2hc) and LAT2-4F2hc. Oocytes expressing LAT1-4F2hc or LAT2-4F2hc demonstrated enhanced uptake of [(14)C]MeHg when administered as the L-cysteine or D,L-homocysteine complexes, but not when administered as the D-cysteine, N -acetyl-L-cysteine, penicillamine or GSH complexes. Kinetic analysis of transport indicated that the apparent affinities ( K (m)) of MeHg-L-cysteine uptake by LAT1 and LAT2 (98+/-8 and 64+/-8 microM respectively) were comparable with those for methionine (99+/-9 and 161+/-11 microM), whereas the V (max) values were higher for MeHg-L-cysteine, indicating that it may be a better substrate than the endogenous amino acid. Uptake and efflux of [(3)H]methionine and [(14)C]MeHg-L-cysteine were trans -stimulated by leucine and phenylalanine, but not by glutamate, indicating that MeHg-L-cysteine is both a cis - and trans -substrate. In addition, [(3)H]methionine efflux was trans -stimulated by leucine and phenylalanine even in the presence of an inwardly directed methionine gradient, demonstrating concentrative transport by both LAT1 and LAT2. The present results describe a major molecular mechanism by which MeHg is transported across cell membranes and indicate that metal complexes may form a novel class of substrates for amino acid carriers. These transport proteins may therefore participate in metal ion homoeostasis and toxicity.

PMID: 12117417