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PyritinolWhat is Pyritinol?

Pyritinol (5,5’-[dithiobis(methylene)]bis[4-(hydroxymethyl)-2-methylpyridin-3-ol] or pyridoxine disulfate) is a water-soluble, semi-synthetic pyrithioxine derivative originally created by Merck in the early 1960s. It is often touted as “the oldest nootropic” because it preceded piracetam. It consists of 2 vitamin B6 molecules that are joined with a disulfide bridge. Although it is related to vitamin B6, the effects are different; pyritinol does not possess B6-like activity.

Beginning in the 1970s it was prescribed for cognitive disorders and has been marketed as Bonifen, Cerbon-6, and Encephabol. Pyritinol is currently available in more than 50 countries, is commonly prescribed in Europe, and has been sold as a nootropic dietary supplement in the U.S. since the early 1990s. The U.S. Food & Drug Administrations does not have an official position on the compound.

How does it work?

The primary mechanisms of pyritinol are increased neuronal glucose uptake and antioxidant activity. Maximizing glucose uptake is important in the brain, because it is unable to use other energy sources (e.g., proteins and fats) as fuel. In addition, it is a very active organ that generates many reactive oxygen and nitrogen species (ROS and RNS). Pyritinol’s antioxidant abilities help to neutralize these harmful molecules, preventing them from oxidizing and damaging cell membranes.

Research in animal models showed that pyritinol increase the level of adenosine triphosphate (ATP) in blood. This molecule is the main energy form utilized by all cells in the body, and the observed effect of greater ATP levels may contribute to pyritinol’s effect on cognition.

Pyritinol also seems to increase choline metabolism and activity. How exactly this occurs is not well understood, but augmented cholinergic signaling in the brain can improve attention and focus.

Pyritinol Benefits

People who take pyritinol as a cognition enhancer claim that it improves recall, increases energy, and enhances mental acuity and reaction time. A study of 12 healthy males reported that reaction time and visual attention scores improved following 3 days of 600- or 1,200- mg doses. It is also said to increase neuron firing rates and glucose metabolism. However, properly randomized clinical studies in healthy populations are limited.

In Europe, pyritinol is used to treat stroke, dementia, traumatic brain injury, encephalitis, and even childhood learning disorders (e.g., dyslexia and autism).

Pyritinol has antioxidant activity and may also improve immune system function (by increasing neutrophils, a specific type of white blood cell). For these reasons, it is sometimes used as a treatment for rheumatoid arthritis (RA). In fact, study has shown that it is more effective than auranofin, an RA-specific drug, in treating symptoms associated with the disease.

Studies in dementia patient populations have been mixed. A 12-week double-blind study found that pyritinol was superior to placebo in 3 separate assessments of cognition, and it improved brain activity associated with vigilance as assessed by electroencephalogram (EEG). Other studies did not replicate this finding.

Pyritinol has been useful in individuals who suffered a traumatic brain injury. One study examined 270 patients who had suffered different types of brain injury and found that a 6-week regimen of pyritinol (600 mg/day in 3 divided  oral doses) significantly improved clinical and psychoneurological manifestations when compared to placebo therapy.

Pyritinol Side Effects

Pyritinol is well tolerated by most people, and few side effects have been reported. Mild to moderate headaches are the most common adverse effect reported by pyritinol users. Others have developed skin rashes during a pyritinol regimen.

Rarely, severe cholestatic hepatitis and acute pancreatitis have been associated with pyritinol use. These side effects seem to be limited to individuals who have reactive immune responses to the compound and are unlikely to occur is most people.

Brain Games

Pyritinol Dosage

Pyritinol is available in capsule and powder formulations. The most common dosing regimen is 600 mg/day in divided doses (200 mg in the morning, at noon, and in the late afternoon). Capsules are usually 100-200 mg (1-3 per day); an equivalent powder dose would be 1/8 or 1/4 of a teaspoon. Both forms should be taken with water and possibly a small amount of food, which may help alleviate some of the gastrointestinal side effects. Because some users may experience insomnia, it should not be taken in the evening.


Fischhof, P.K., B. Saletu, E. Rüther, G. Litschauer, R. Möslinger-Gehmayr, and W.M.. Herrmann. “Therapeutic Efficacy of Pyritinol in Patients with Senile Dementia of the Alzheimer Type (SDAT) and Multi-infarct Dementia (MID).” Neuropsychobiology 26.1-2 (1992): 65-70. Print.

 Greiner, H., A. Haase, and C. Seyfried. “Neurochemical Studies on the Mechanism of Action of Pyritinol.” Pharmacopsychiatry 21.S 1 (1988): 26-32. Print.

 Hindmarch, I., D.M. Coleston, and J.S. Kerr. “Psychopharmacological Effects of Pyritinol in Normal Volunteers.” Neuropsychobiology 24.3 (1990): 159-64. Print.

 Kitamura, K. “Therapeutic Effect of Pyritinol on Sequelae of Head Injuries.” Journal of International Medical Research 9.3 (1981): 215-21. Print.

 Lemmel, E.-M. “Comparison Of Pyritinol And Auranofin In The Treatment Of Rheumatoid Arthritis.” Rheumatology 32.5 (1993): 375-82. Print.

 Maria, V. “Severe Cholestatic Hepatitis Induced by Pyritinol.” BMJ 328.7439 (2004): 572-74. Print.

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