Paracetamol is possibly the most common painkiller used today, it in most peoples homes and at the slightest sign of a headache people will take it without a second thought. All most people know is that paracetamol offers affective pain release, and it is a common belief that because it is so easy to purchase over the counter, it is safe. This article will explain how paracetamol works in the body, and review the use of paracetamol on our health. Is paracetamol safe?

How paracetamol works

Surprisingly, the mechanism by which paracetamol works is not fully understood. It is thought that paracetamol inhibits a group of enzymes called COX, which are responsible for making pro-inflammatory molecules. Paracetamol has very mild inhibitory effects on COX-2 and COX-3, and only has an impact on COX-1, which makes its anti-inflammatory properties minimal. This mechanism would also only be significant if the cause of pain was inflammation, which may not always be the case.

Another, and more probable proposed mechanism, is its effects in the endogenous cannabinoid system, which is a system responsible for modulating pain as well as mood, appetite and to some extent our memory. Paracetamol is broken down in the body into a compound which is called AM404. AM404 inhibits the uptake of neurotransmitters in the nerves of this endogenous cannabinoid system, which reduces the signalling to the brain, which will be perceived as a reduction in pain. Paracetamol itself doesn’t cure the cause of the pain, it simply stops us feeling pain.

Infrequent use of paracetamol will have no significant or long term effects on a healthy individuals health. However regular use, which can be as regular as once a week, can have an impact on a number of biological systems, which is of particular concern for some groups of people.

Bone metabolism – We know that paracetamol effects the COX family of enzymes, and endogenous cannabinoid system, which may affect signalling in bone cells and influence bone metabolism and density. To investigate this possibility a study was conducted in 2011, which investigated the incidence of bone fracture with paracetamol consumption. The results showed that those participants who consumed paracetamol regularly had a higher incidence of bone fractures, this difference was still significant when adjustments were made for ages, diet, activity, weight and if they smoked. These results are of particular concern for women over the age of 50 who are a high risk of osteoporosis and so a high risk of bone fracture as it is.

Liver damage – As little as 150mg/kg body weight in one serving can be fatal for most people, which for a 70kg male is 10.5g, but it could be much less for those with damaged livers. When paracetamol is consumed in small dosages it is often converted in non-toxic compounds via phase Ⅱ metabolism. This is simply a method the liver uses to neutralize drugs that have entered out system, however, phase Ⅱ cannot process large amounts of drugs at one time, and can easily become saturated with large dosages of paracetamol, which means not all the paracetamol consumed can be neutralized by this pathway. The amount of paracetamol thought to saturate phase Ⅱ is 7g a day for the average healthy individual but there is variance from person to person. The excess paracetamol will be converted into a highly reactive and toxic compound which is called NAPQI, which in turn must be neutralized by glutathione. Glutathione is in limited supply in the liver and is quickly used up in neutralizing NAPQI. Levels of glutathione can be low if alcohol or any substance which taxes the liver is regularly consumed. Once levels of glutathione are depleted, levels of the highly reactive NAPQI will continue to build up, and cause sever liver damage.

Although 10.5g is a large amount, regularly taking paracetamol throughout the day for an extended period of time can have a similar effect, as levels of glutathione can still deplete, and are replenished very slowly. It is therefore not recommended to consume low dosages regularly.

It is concerning that the way in which paracetamol works in the body is not fully understood, especially considering its wide and ‘care-free’ use by the public. Current evidence shows that infrequent and low dosage use of paracetamol is safe for the majority of people. Regular usage should not occur though, and this is because it is known to inhibit neurotransmitters in the cannabinoid system, which if regular, can reduce bone mineral density resulting in an increased risk of bone fracture. This is of particular concern for women over the age of 50, who are at a high risk of bone fracture as it is.

We also know that regular/ large dosages of paracetamol can cause liver damage, and is of concern for those who may have a damaged liver or regularly tax the liver with alcohol or other substances. It is therefore recommended that paracetamol should not be consumed carelessly, and if you are a high risk group, no more than 2-3g a day should be consumed and never on consecutive days.

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