1. Patients launch $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
Brain Cells Making us Sick? The microglia connection in ME/CFS & Fibromyalgia
Simon McGrath looks at theories that microglia, the brain's immune cells, could trigger and perpetuate the symptoms of ME/CFS and fibromyalgia.
Discuss the article on the Forums.

N-Acetylcysteine

Discussion in 'Other Health News and Research' started by heapsreal, Aug 14, 2012.

  1. heapsreal

    heapsreal iherb 10% discount code OPA989,

    Messages:
    7,103
    Likes:
    4,349
    australia (brisbane)
    http://www.pspinformation.com/nutrition/aminoacids/nac.shtml
    I hope this is of interest.



    Introduction

    N-Acetylcysteine also know as N-Acetyl Cysteine or NAC is a version of the amino acid L-Cysteine. It is a powerful antioxidant and a premier antitoxin and immune support substance.


    The principal value of NAC covered here is as a nutritional supplement to help the liver create a substance called glutathione. Both Cysteine and Methionine are good precursors of glutathione, but NAC is better. L-Cysteine loses approximately 85% of its sulfur group (which becomes the active part of glutathione) in the digestion process, while NAC, a more stable compound, loses only 15%. This means that NAC has almost six times more effective sulfur groups left after digestion.


    Glutathione

    Glutathione is a tri-peptide composed of three amino acids: Cysteine, Glutamic Acid and Glycine. Glutathione and the enzymes it forms, such as Glutathione peroxidase, are essential to all life and are found in tissues of virtually all plants and animals. Glutathione peroxidase is one of the body's most important naturally occurring antioxidants.
    Glutathione is present in all human cells, with the highest levels found in the liver, lung, lens of the eye, pancreas, spleen and kidneys. Since glutathione is such an vital naturally occurring antioxidant, NAC is now considered a potent protective agent in many diseases and conditions in which reactive oxygen molecules (free radicals) play a role.
    Glutathione is a key protector against all types of pollution. Glutathione protects against cellular peroxidation caused by exposure to pesticides, toxic herbicides like paraquat, plastics, benzene and carbon tetrachloride. It also protects against the toxic effects of heavy metals, cigarette smoke, smog, drugs like Tylenol (acetominophen), solvents, dyes, phenols and nitrates, and the side-effects of anti-cancer drugs like cyclophosphamide and adriamycin.
    Glutathione works to inhibit the formation of free radicals, dangerous agents that suppress the immune system and promote the formation of mutagens and carcinogens. Free radicals also speed up the aging process, and it is due to this antioxidant activity that Glutathione is considered useful in the prevention and treatment of a wide range of degenerative diseases. Supplemental N-Acetyl Cysteine may exert its anti-aging effect by increasing glutathione levels.
    Studies at the Louisville School of Medicine have shown that Glutathione possesses a unique ability to slow the aging process. While Glutathione aids in the protection of all cells and membranes, a study at Harvard Medical School found that glutathione is especially able to enhance immune system cells, protecting against damage from radiation and helping to reduce the side effects of chemotherapy, x-rays, and alcohol.
    NAC, cysteine and reduced glutathione all have properties that act to help repair oxidative damage in the body. All are well absorbed. NAC is rapidly metabolized, and only about ten percent of the amount consumed stays in the blood for an appreciable time. Much of the NAC is very rapidly consumed in producing intracellular glutathione. However, even the thiol metabolites of NAC are good antioxidants.
    NAC readily crosses cell membranes and does not seem to raise tissue or blood levels of glutathione above the desired ranges. Thus, the nutrient role of NAC is to help maintain healthy levels of intracellular glutathione , especially whenever a condition has limited glutathione production. This nutrient role of maintaining optimal levels of essential body compounds is different from "drug roles" in which body compounds are just elevated without homeostasis or normal body regulation.
    NAC, cysteine and glutathione contain sulfur in the form of sulfhydryl groups. Sulfhydryl groups directly react with many poisons, especially heavy metals such as lead, mercury and cadmium. These sulfur-containing nutrients are the body's first line of defense against many poisons as they tie-up the poisons right in the gut. They also offer second-line and third-line defenses in the liver and various individual cells. Sulfhydryl groups also help remove toxins indirectly via an enzyme system called the P-450 System.
    NAC also has a secondary role in detoxification since it helps produce optimal amounts of glutathione which also conjugates with most "foreign" compounds and excess oxidizers that enter cells. The harmful compounds that have been conjugated with glutathione then pass harmlessly out of the body through the biliary system.


    Metabolism of NAC

    NAC is easily absorbed through oral administration, with blood levels peaking within an hour. NAC is metabolized in the gut wall and liver and is converted to L-cysteine, and ultimately, from cysteine into glutathione. Oral NAC has been shown to increase glutathione levels in numerous different tissues of the body in both animals and humans.
    At 12 hours post-dose it is undetectable in plasma. Despite a relatively low bioavailability of only four to ten percent, oral administration of NAC appears to be clinically effective. The biological activity of NAC is attributed to its sulfhydryl group, while its acetyl substituted amino group affords it protection against oxidative and metabolic processes.


    Mechanisms of Action

    NAC's effectiveness is primarily attributed to its ability to reduce extracellular cystine to cysteine, or to act intracellularly as a source of sulfhydryl groups. As a source of sulfhydryl groups, NAC stimulates glutathione (GSH) synthesis, enhances glutathione-S-transferase activity, promotes liver detoxification by inhibiting xenobiotic biotransformation, and is a powerful nucleophile capable of scavenging free radicals. NAC's effectiveness as a mucolytic agent results from its sulfhydryl group interacting with disulfide bonds in mucoprotein, with the mucus subsequently being broken into smaller, less viscous units. NAC may also act as an expectorant by stimulating both ciliary action and the gastro-pulmonary vagal reflex, thereby clearing the mucus from the airways. Studies have also shown NAC to be of benefit in heart disease by lowering homocysteine and lipoprotein(a) levels via dissociation of disulfide bonds,protecting against ischemic and reperfusion damage via replenishment of the glutathione redox system,as well as potentiating the activity of nitroglycerin.


    Clinical Indications

    Respiratory Illness

    Several animal and human studies have explored NAC's effectiveness as a therapeutic agent for various types of respiratory illness. While results varied, NAC administration resulted in decreased expectoration difficulty, cough severity,and diaphragm fatigue. A small study was conducted with 18 patients diagnosed with fibrosing alveolitis; a condition characterized by severe oxidative stress and decreased glutathione levels. NAC was administered at a dose of 600 mg three times daily for 12 weeks and improvement in both pulmonary function and glutathione levels was noted. In contrast, studies of patients with chronic bronchitis, severe airway obstruction, and cystic fibrosis showed a slight, although not statistically significant, decrease in the exacerbation rate.


    HIV Infection

    Human immunodeficiency virus (HIV)-positive individuals usually exhibit low GSH and cysteine levels, prompting studies on NAC's effectiveness as a therapeutic tool for these patients. Research suggests that NAC is capable of enhancing T cell immunity by stimulating T cell colony formation,and blocking NF kappa B expression. In a double-blind, placebo-controlled trial Akerlund et al found NAC to positively impact both plasma cysteine levels and CD4+ lymphocyte cell counts. More studies are needed but it appears that if given to HIV-positive patients early in the course of disease, NAC may help to prevent progression to AIDS.


    Cancer/Chemoprevention

    Research has shown NAC to have potential both as a chemopreventative agent and a treatment in certain types of cancer, including lung, skin, head and neck, mammary, and liver cancer. In vitro studies have demonstrated NAC to be directly anti-mutagenic and anti-carcinogenic as well as inhibiting the mutagenicity of certain compounds in vivo. Research also indicates NAC administration in both cell cultures and animal studies selectively protects normal cells, but not malignant ones, from chemotherapy and radiation toxicity. Other in vitro studies noted NAC's effectiveness at inhibiting cell growth and proliferation in human melanoma, prostate, and astrocytoma cell lines.


    Acetaminophen and Other Poisonings

    The discovery that NAC (and the glutathione formation it promotes) is an effective antidote for acetaminophen poisoning first indicated NAC's importance as an antioxidant. Acetaminophen is a commonly used pain reliever that until recently was considered safe in small commonly used doses. Now new research tends to cast a doubt that the drug is completely safe at any dosage level. Acetaminophen is the main ingedient in many over-the-counter drugs both branded and generic - the principal brand being Tylenol. There is some disagreement about the safety of acetaminophen in small doses so consider that the jury is still out.
    We do know that ingestion of 10-15 grams of acetaminophen in a single dose can result in liver damage or failure and death 2-5 days later unless NAC is given to the patient within within 12 hours of the acetaminophen ingestion. NAC is not effective if given later than 12-16 hours since the although the glutathione can prevent oxidant-derived cellular damage, it cannot reverse cell death that has already occurred.
    Generally we recommend not using acetaminophen if something else is readily available. Since NAC and acetaminophen cancel the effects of each other the use of acetaminophen will limit any benefits you might expect from your use of NAC. Adversely, if you must take acetaminophen for some reason it would be very wise to also take NAC in an attempt to prevent possible liver or/and kidney damage.


    NAC as an Antioxidant

    Antioxidants neutralize free radicals, which are produced by normal metabolic activity. When free radicals are left unchecked they cause damage to cells and DNA and are considered by scientists to be a major factor in the cancer and aging processes.
    NAC has the capacity to scavenge hydrogen peroxide hypochlorous acid, and the hydroxyl radical, but most of its antioxidant value is due to its promotion of glutathione formation. This activity of NAC protects membranes from damage by superoxide radical systems. NAC is receiving growing interest from both scientists and physicians, due to the enormous role that oxidation and free-radical mediated damage play in many diseases.
    NAC directly detoxifies reactive oxygen mutagens such as superoxide, hydrogen peroxide, and singlet oxygen, and inhibits environmental carcinogens such as cigarette smoke condensate and aflatoxin. Within cells, NAC is rapidly converted to cysteine and then to glutathione which detoxifies carcinogens inside cells and helps decrease carcinogen-induced DNA damage. In its role as an inhibitor of DNA mutations in various organs and tissues, NAC and glutathione may prove potent protectors of a wide variety of diseases.
    (NAC should be used with caution by diabetics as it may reduce certain disulphide bonds that determin the structure of insulin. Have a blood test to rule out diabetes if you are uncertain).
    NAC has also been effective for heavy metal poisoning by gold, silver, copper, mercury, lead, and arsenic, as well as in cases of poisoning by carbon tetrachloride, acrylonitriles, halothane, paraquat, acetaldehyde, coumarin, and interferon. Studies involving these poisons are primarily animal studies or single case reports and therefore additional studies are needed to establish NAC's effectiveness in this area.


    Heart Disease

    Several small clinical studies have demonstrated that NAC may be an effective therapeutic agent in the management of heart disease. Wiklund et al demonstrated NAC's ability to reduce plasma homocysteine levels by 45 percent, while Gavish and Breslow demonstrated NAC (2-4 grams daily for eight weeks) was able to reduce lipoprotein(a) by 70 percent. Due to its ability to significantly increase tissue GSH, NAC may also be useful in treating the ischemia and reperfusion seen in acute myocardial infarction, and the resultant depletion in cellular sulfhydryl groups. In addition, NAC appears to potentiate nitroglycerin's coronary dilating and anti-platelet properties and therefore may be a useful combination therapy in-patients with unstable angina pectoris and myocardial infarction.


    Other Clinical Indications

    Clinical studies have also demonstrated NAC's therapeutic benefit in the treatment of Sjogren's syndrome, myoclonus epilepsy,influenza, illness associated with cigarette smoking, hepatitis C and myoclonus epilepsy.


    Dosage

    Usage as a mucolytic agent or as a treatment are the only uses presently accepted as medical treatments and for these NAC is available as a prescription medication.
    For all other usages it is available as a food supplement in health food stores and locations that sell supplements including vitamins.
    In most cases NAC and L-Cysteine are interchangable. NAC is thought to be more effective for most usages, to taste somewhat better and is often cheaper. Compare prices.
    There are differences in opinion on whether glutathione has any value as an oral supplement. Some claim that by the time glutathione is digested and into the bloodstream it is no longer glutathione. They claim that it is better to take NAC or L-Cysteine and let the liver convert them to glutathione.
    The typical oral dose for NAC as a mucolytic agent and for most other clinical indications is 600-1500 mg NAC daily in three divided doses. In patients with cancer or heart disease the therapeutic dosage is higher, usually in the range of two to four grams daily. For acetaminophen poisoning, NAC is usually administered orally with a loading dose of 140 mg/kg and 17 subsequent doses of 70 mg/kg every four hours. In acetaminophen poisoning, it is important to begin administering NAC within 8-10 hours of overdose to ensure effectiveness.
    Although NAC is a food component and a nutrient accessory factor, it is also marketed as a drug with approved medical claims. It has been typically been utilized at dosages from 200 mg to 1200mg per day. Higher doses have been utilized in more severe disease states, but for general use as an antioxidant, most would want to consume from 200 mg to 600 mg daily. People exposed to large sources of oxidants and glutathione depleters, such as smokers or drinkers would probably want to use NAC at the upper level of this range. No NAC-associated toxicity has been reported.
    It is preferable to purchase amino acids from a source where you know they are fresh and have not been on the shelves for a long time.
    Though toxicity at normal dosages has not been proven to be a problem, it is recommended that supplemental dosages be given under the supervision of a health professional.
    Recent studies indicate that other antioxidants, such as vitamin C, vitamin E, and selenium also play a role in the metabolism and regeneration of glutathione and may work synergistically to enhance NAC's properties.


    Safety and Side-Effects

    NAC is generally safe and well tolerated even at high doses. The most common side-effects associated with high oral doses are nausea, vomiting, and other gastrointestinal disturbances, and therefore oral administration is contraindicated in persons with active peptic ulcer. Infrequently, anaphylactic reactions due to histamine release occur and can consist of rash, pruritis, angioedema, bronchospasm, tachycardia and changes in blood pressure.
    Intravenous administration has, in rare instances, caused allergic reactions but they are generally in the form of rash or angioedema. NAC is "Ames test" negative but animal studies on embryotoxicity are equivocal. In addition, studies in pregnant women are inadequate so NAC administration during pregnancy should be with caution and only if clearly indicated.
    Oral administration of NAC and charcoal at the same time is not recommended, as charcoal may cause a reduction in the absorption of NAC. In addition, as with any single antioxidant nutrient, NAC at therapeutic doses (even as low as 1.2 grams daily), has the potential to have pro-oxidant activity and is not recommended at these doses in the absence of significant oxidative stress.
    NK17, JBB, Marco and 3 others like this.
  2. heapsreal

    heapsreal iherb 10% discount code OPA989,

    Messages:
    7,103
    Likes:
    4,349
    australia (brisbane)
    I have been using NAC for a long time as well as lipoic acid and other antioxidants. I wonder if this is why i dont notice any results from methylation type protocols b12/methyl folate etc as NAC is doing a good job on its own?? and maybe protected me in some way that i dont have a partial methylation block problem?? where i dont need b12/folate. I used NAC pre cfs, maybe a different story if i wasnt using NAC then.

    At the end of the day oxidative stress is shown to be high in cfs/me and any way to increase our antioxidants/glutathione is a good thing. It would be interesting to see the difference between those regular uses of nac and those who dont and the treatment effects between them on the partial methylation protocol. At a guess i think the ones who arent regular uses of nac will benefit from partial methylation protocol.

    cheers!!!
    JBB, Allyson and Jarod like this.
  3. ggingues

    ggingues $10 gift code at iHerb GAS343 of $40

    Messages:
    3,918
    Likes:
    784
    Concord, NH
    Can you break up your first posting more to make it easier to read? perhaps it is a software glitch? Thought I would ask.

    GG
    SOC likes this.
  4. Lala

    Lala Senior Member

    Messages:
    317
    Likes:
    57
    EU
    That is very interesting, heapsreal. I was also on high dose NAC for a few years and now, when I take methylfolate and methylcobalamin, I do not feel any dramatic effect, though I like methylfolate better than folic acid.
    heapsreal likes this.
  5. jimmy86

    jimmy86

    Messages:
    47
    Likes:
    33
    I was on NAC for 6 month (and B12, L-Carnitin, Q10) but did not see any difference from it...
  6. adreno

    adreno 3% neanderthal

    Messages:
    2,193
    Likes:
    1,261
    Tundras of Europa
    NAC works well for me, I take 500mg twice daily.
  7. Sallysblooms

    Sallysblooms P.O.T.S. now SO MUCH BETTER!

    Messages:
    1,767
    Likes:
    327
    Southern USA
    :thumbsup: My doctor has it on my supplement schedule. I take NAC every day!:thumbsup:
  8. August59

    August59 Daughters High School Graduation

    Messages:
    1,479
    Likes:
    401
    Upstate SC, USA
    My memory may be wrong here, but was it Rich or Fredd that had a theory as to why we shouldn't take NAC while doing a methylation protocol. I can't think of a reason why, but I felt sure I read it somewhere. It may have had something to do with BBB. Does NAC cross the BBB?
  9. richvank

    richvank Senior Member

    Messages:
    2,717
    Likes:
    738
    Hi, August59.

    If it was I, the issue was that if there is a high body burden of mercury, too high a dosage of NAC can move mercury into the brain. Dr. David Quig of Doctor's Data Lab has written that the dosage should be limited to 300 mg per day if there is a lot of mercury in the body.

    If it was Freddd, the issue was that Freddd himself is not able to tolerate anything that helps to form glutathione, which NAC does. I think this is unusual with respect to ME/CFS, because the depletion of glutathione is what brings on this disorder, in my hypothesis.

    I think that the problem in Freddd's case is that he has inherited what is referred to in the published literature as a rare mutation in the CblC complemetation group. This is part of the intracellular B12 processing pathway. Normally, glutathiione helps CblC to process B12. However, in Freddd's case, apparently when glutathione combines with B12 to form glutathionylcobalamin, his cells are not able to access the B12, and this makes his B12 status worse instead of better. Freddd does not believe that this is rare, and I think he has found some others that respond in this same way. I haven't run across other cases like this in the ones I have studied.

    Best regards,
    ;
    Rich
    Sallysblooms likes this.
  10. August59

    August59 Daughters High School Graduation

    Messages:
    1,479
    Likes:
    401
    Upstate SC, USA
    Thanks Rich - It just seemed that I had remembered something about NAC and it iwas either not recommended or there was caution in using in a given situation.

    Thanks very much for clarifying this!
  11. physicsstudent13

    physicsstudent13 Senior Member

    Messages:
    225
    Likes:
    5
    it seems that NAFLD/NASH played a role in my chronic fatigue with lowered glutathione and sleep apnea
    does NAC cause heart swelling or hypertension, narrowing of the blood vessels permanently in the lungs? I think NAC has helped me a great deal in the short term in repairing my liver and removing toxins, but I'm not sure if I should continue on it. maybe it's helpful to take it with low dose vitamin E and C?
    there is cysteine absorption disorder which may lower glutathione
  12. heapsreal

    heapsreal iherb 10% discount code OPA989,

    Messages:
    7,103
    Likes:
    4,349
    australia (brisbane)
    I havent had any issues, i have been using 600mg bid for a few years now. I also take a variety of antioxidant/mito supps, vit e(mixed tocerophils), vit c, lipoic acid, q10, acetyl carnitine.

    If your having lung issues, chat to @alex3619 who has had bronchoconstriction issues eased with resveratrol??
    physicsstudent13 likes this.
  13. alex3619

    alex3619 Senior Member

    Messages:
    6,833
    Likes:
    10,404
    Logan, Queensland, Australia
    I have had great effect from resveratrol, at 600mg twice a week or every third day, on bronchorestrictive symptoms. It does thin the blood though so anyone with clotting or bleeding issues should avoid it. Tag me for this thread of anyone wants to hear about my latest thoughts, I am doing a lot of experimenting on myself with different resveratrol protocols.

    2g per week sounds great, but taken every day at about 300mg it does nothing for me. Take 900mg twice a week, and the effect is noticeable. There is a threshold effect. The protective value seems to last around three days, hence my twice a week dosage. I think caution is required as resveratrol makes large changes to the regulation of intracellular chemistry.
    physicsstudent13, Hanna and heapsreal like this.
  14. physicsstudent13

    physicsstudent13 Senior Member

    Messages:
    225
    Likes:
    5
    Thanks very much! I take dulera and singulair and occasionally medrol and combivent on a nebulizer. They have a new medication accolate which I am going to try since everything else has failed. I can't exhale anymore, I just went to the ER from an asthma attack, my throat was closing up and I had headaches and 80% O2 on an oximeter.

    I think you have to be really careful with NAC since it damages the lungs and heart by narrowing the lung airways and thickens the heart wall. I tried to warn everyone here but then they were telling me that they had no problems with it but you cannot really see what it does to your heart and lungs at least without imaging like echocardiograms. I had an echo done and it was normal after taking a lot of NAC but maybe it doesn't show up on imaging

    Last edited: Jul 16, 2014
  15. Valentijn

    Valentijn Activity Level: 3

    Messages:
    5,930
    Likes:
    8,061
    Amersfoort, Netherlands
    Where'd you hear that? Could you provide a citation?
  16. Little Bluestem

    Little Bluestem Senescent on the Illinois prairie, USA

    Messages:
    2,351
    Likes:
    1,681
    Midwest, USA
    Can NAC be taken with food? I thought amino acids were supposed to be taken on an empty stomach, but my bottle does not say so.

See more popular forum discussions.

Share This Page