NAC (N acetyl cysteine)-also apparently lowers triglycerides but I don’t know the dose; NAC helps diabetes
[adding taurine to NAC accentuates the benefit of NAC]

NOTE: Michael Berk, MD did 2 studies with NAC. For depression it no doubt took 5 months to have dramatic benefit because over 90% is metabolized by the liver. In a 2nd study on schizophrenia it had significant benefit in 6 weeks, though the benefit was not as dramatic as it was for bipolar depression. Interestingly, I have had positive benefit in 1-2 weeks with schizophrenia. When I think it has helped depression, it was one month or more–but in 2 bipolar patients it was a very dramatic response in a week from profound depression, and the rapid response was unlike any previous experience with these patients.

MY USUAL INSTRUCTIONS:

Try 7 pills [of 600mg] per day of NAC [N-acetyl cysteine] capsules for 3-4 months, — or use 4 grams of powder {put 1½ teaspoons in liquid or in yogurt}. In 3 to 4 months, if it seems to be helping, we may try to  it to ½ dose—i.e., 4 pills or ¾ teaspoon. If it seems not to help, we may stop it abruptly to see if there is a difference.
NAC works better if you take vitamin C also: I suggest 1000mg with the NAC dose.

SOURCES of NAC:

it is available in all health food stores but costs about $60/month, and from companies such as below it costs about $10.00 +/month. POWDER: 500 grams of NAC powder for $34.99, at www.bulknutrition.com [on that website pick category “bulk amino acids”  then scroll down to N-acetyl cysteine] PHONE: 800-975-8125 [BulkNutrition.com 455 Whitney Street Northborough, MA 01532] You would take 4 grams per day; ask a pharmacy for a measuring spoon. Mix it in juice or diet soda to drink. I find yogurt works the best, and it still tastes too bad, then add jam to the yogurt. 1½ teaspoons is about the right dose. If you use 4 grams per day $34.99 will buy you a 4 month supply. CAPSULES: From various sites you can get pills that cost about $10 for #240, including www.bulknutrition.com. Source Naturals has 1000mg pills—then you would only swallow 4 pills/d. #120 for $21 on Amazon. (Or $17.67 if you get it automatically sent at regular intervals – no shipping.)

INFORMATION SHEET on NAC / N-acetyl cysteine

 Formerly I recommended Dr Michael Berk’s research dose: N acetyl cysteine (NAC) 600mg or 500mg pills : 2 pills twice a day–i.e., 1200mg 2x/ day or 1000mg 2x/ day [note: it is called either acetyl cysteine or N-acetyl cysteine]. But now I recommend 8 pills per day, as it took some 5 months to work in most people on 4 pills/day. This is an amino acid that was recently shown to definitely help depression [it was compared to a placebo].

It is a nutrient naturally found in humans– we make it ourselves and it is present in small amounts in the meat we eat. A summary of the study was briefly presented at an international conference in Pittsburgh in June, 2007 by the primary investigator, Michael Berk, MD. He is a professor at the medical school of Melbourne University in Australia, designed the study based on basic science.

Neuroscientists have determined that in bipolar depression there is significant oxidative stress in the brain, which means more rapid metabolism producing excessive free radicals [which are toxins/poisons we produce and must neutralize]. Glutathione is the most important free radical scavenger [antioxidant] in the body [i.e., it cleans the body of these highly charged, toxic chemicals]. Glutathione itself is a combination of 3 amino acids [the middle one being cysteine], and is thus too large to pass the blood brain barrier. It is present in virtually all cells, including red blood cells, and is important to mlaintain cell health. Brain cells make their own glutathione. It has been known for years that if you administer the amino acid N-acetyl cysteine {NAC}, cells use it to produce more glutathione. NAC is small enough to pass the blood brain barrier. Glutathione is not well absorbed by the stomach. Nor does it cross the blood brain barrier.

 It was a 6 month study. [The study is not published yet, but the abstract of the study is below.] For the 1st 5 months the patients on NAC did about the same as the patients on placebo [they did better numerically than placebo, but it was not statistically significant]. After 5 months, the patients on acetyl cysteine suddenly did dramatically better than people on placebo on 8 different scales–mostly measures of depression and overall functioning–and maintained that benefit for the two weeks remaining in the study. When the study was stopped the responders gradually lost the benefit and a month later were at the same level of depression as the patients on placebo. I suspect the reason for the 5 ½ month delay in benefit is because the dose was too low. NAC is rapidly metabolized, and only about ten percent of the amount consumed stays in the blood for an appreciable time–and some authorities say only 2 to 5%. Thus, of a 2000mg dose, only 200mg stays in the blood for an appreciable time, and only a fraction of this enters the brain. I suspect 4000mg [4 grams/day] would be a better dose.

 This is practically the first time a treatment in psychiatry was devised by looking at the mechanism of the disorder first, and then postulating a place to intervene–whereas all other treatments in psychiatry were found by accident. Later, better drugs have been “me-too” drugs designed to mimic the original ones.

SIDE EFFECTS:

The only side effect I have seen is dyspepsia infrequently — which means an upset stomach. NAC in normal food supplementation ranges is without known toxicity and has been administered by physicians under supervision in doses of 500 milligrams to four grams daily. Daily levels of 1,000 milligrams of NAC per kilogram in rats for several months did not produce adverse effects in behavior, weight gain, hematology, liver function and kidney function. (That’s the equivalent of 60 grams/ 120 pills of NAC per day for a 132 pound person.) Larger quantities used for treating acetaminophen [paracetamol or Tylenol] overdoses have produced adverse reactions such as nausea, vomiting, and other gastrointestinal symptoms–and sometimes allergic reactions. The does for treatment of acetaminophen/ Tylenol overdose is quite high. For a person weighing 220 lbs, the dose of NAC / acetyl cysteine is 15 grams initially and then 7.5 grams grams every 4 hours for 3 days [17 doses] = 142.5 grams = 285 of the 500mg pills in 3 days–i.e., over 90 pills [45 grams] per day. When it is given to drink as a liquid, it is usually mixed with coca cola.

THE ABSTRACT OF THE STUDY:

Antioxidant treatment of the glutathione deficiency in bipolar disorder with n-acetyl cysteine: a double blind randomized placebo controlled trial. M Berk DL Copolov a, 0 Dean a,b K Lu a C S Jeavons’, I Schapkaitz “ MA Hunt Al Bush ‘Mental Health Research Institute of Victoria, b University of Melbourne, C Barwon Health, d Orygen Youth Health, Australia. Background: Oxidative stress is documented to occur in bipolar disorder. Existing mood stabilisers have effects on oxidative biology. Glutathione is the body’s major endogenous free radical scavenger. N-acetyl cysteine (NAC) is a tolerable, orally bioavailable precursor of glutathione. Methods: In a randomized, double-blind, multi-center, placebo-controlled study, we evaluated 75 individuals with bipolar disorder who were treated with NAC (1 gram BID) as an add-on to their usual mood stabilizer medication over a 6 month period, followed by a 4 (± 2) week washout. Outcome measures included the MADRS, BDRS, YMRS, CGI-l and CGI-S, CGI-BP and a modified CGI for substance use, GAF, SOFAS, SLICE LIFE, LIFE RIFT, LFQ and Q-LES-Q. Results: NAC treatment led to a significant improvement on the BDRS, MADRS, CGI-BP, GAF, SOFAS, Q-LES-Q, LIFE RIFT and SLICE LIFE at trial endpoint (week 24). At the one month post discontinuation visit there was no longer any significant difference between the groups on any of the outcome measures. There were no significant between group differences in treatment emergent adverse events. A calculation of effect sizes revealed significant improvements in the medium range, from 0.3930 to 0.64. Conclusions: NAC is a novel, efficacious and tolerable therapeutic option for bipolar disorder, which is safe affordable and readily available. In particular, it ameliorates depressive symptoms in the maintenance phase, addressing a major unmet need.
—-There was a report of it working for nail biting.

For liver toxicity secondary to acetaminophen overdose, NAC is used: about 1500mg of NAC p.o. every 4 hours x 18 times= 27,000 mg in 3 days, about 9000mg/day.

In a study treating severe alcoholic hepatitis (NEJM 11/10/11, p 1781), the maximum NAC used was 100mg/kg I.V. over 16 hours. For a 70 kg person, that would be 7000mg, which is equivalent to 70,000 mg p.o.—i.e., 70 grams vs the 4 grams I suggest.