Caution

Acetaminophen, also known as paracetamol (and by the trade name Tylenol™), is found to have “more risks” than previously thought, especially at the high end of the standard recommended dosage stated on the label. And perhaps even at lower standard dosages if you take it along with certain supplements.

Caution is now the watchword. More side effects of drugs we have come to respect and use with a “sense of safety” come to light daily. And at the same time we are made to be more fearful of nutrients, herbs and diets, when often, not always, they have a better safety profile.

Paracetamol is the most widely used over-the-counter (OTC) and prescription medication for pain worldwide. The World Health Organization has guidelines for pain control called a  “pain ladder” algorithm (formula) for treating pain and they routinely place Paracetamol as the 1st rung of choice. Diverse international guidelines for acute and chronic painful conditions also recommend the same .

A new study in the Annals of Rhematic Diseases published on March 2, 2015 suggests caution is warranted with daily use of acetaminophen even at dosages said to be safe on the label. This study examined every study from the time this drug came on the market up till May 2014 to take a look at acetaminophen’s safety status.

Emmert Roberts, from South London and the Maudsley Mental Health Trust, Maudsley Hospital, London, United Kingdom, and colleagues analyzed 1888 English articles on paracetamol that looked at its links to mortality, cardiovascular, gastrointestinal, or renal adverse events.

Eight studies met the researcher’s in-depth criteria which were: participants had to be adults over 18 years, had to be taking paracetamol orally, in a standard therapeutic dose such as 500 to 1000 mg every 4-6 hours and not going over the suggested maximum of 4/day.

All the studies were cohort studies. This type of study follows groups of people for a period of time who do not have an issue or disease and then identifies who develops a problem. These studies are observational and warnings from these studies, statisticians say, should be taken with a grain of salt, but perhaps a large enough grain to hit you in the head and stun you.

These studies are not what is called “hard data,” like a randomized controlled trial (which can have their issues too, remember the ill-fated hormone arm of the Women’s Health Initiative), but this review is still a very in-depth look-see into almost 2000 articles. In reviewing acetaminophen, these researchers decided not to include randomized controlled trials because they wrote that these trials go on too short to identify long-term effects and are not representative of the general population.

Findings

Mortality. Two studies of the eight studies examined death risk in adults who took paracetamol compared to those who did not. Those who took this medication died statistically earlier than those who did not. In another study, in folks taking standardized doses, the risk of mortality from all causes was higher.

Heart. Four of the eight studies linked paracetamol to heart health. All found a dose-response, meaning the more you took of this med, the more issues you might have with your heart.  One study showed an increased risk of all cardiovascular events at all dosage levels.

Gastrointestinal tract. What about the gut? One study linked all dosages to increasing likelihood of multiple gut problems including  ulcers and bleeding (and you would be shocked at how much inflammation, ulceration and even bleeding can occur without black, tarry stools or pain.) In researching and writing my new gut book, I found that many medications which  you wouldn’t first think of as possibly hurting the gut, can and do, and often silently. These meds range from painkillers such as aspirin and paracetamol to the benzo and anti-depressant families. There is no drug that we don’t pay some price for if we take it continually, and the gut is often left with the check.

Gut links. Remember, the gut contains 70-80% of the entire immune system. It is derived embryologically from the exact same cells as the brain. It is the second brain. Gut hunches are real. Gut health influence is global in the human body. Any continual use of a drug such as paracetamol that tamps down this system, affects all bodily systems, but especially immune and neurologic.

Renal health. What about the kidney? Nephrologists (kidney doctors) tell patients with any chronic kidney disease to avoid nonsteroidal anti-inflammatories and instead use Tylenol. I have recommended the same, having worked in a dialysis practice for a bunch of years . Four studies linked nasty kidney effects from paracetamol with a decrease in demonstrable filtering functionality of the kidney. This was tracked by a blood test called the estimated glomerular filtration rate (eGFR).

Pause…

Doesn’t this information make you pause before you pull out a bottle of Tylenol for a headache? Or if you have kidney disease, or heart disease, does it give you discomfort to regard this old time pain reliever friend, as harmless?

Drugless interventions. What this “screams out loud” is that it makes sense to try non-medication ways of relieving pain first! That is what chiropractic, naturopathy, acupuncture and nutrition have been about for decades.

Magnesium, Nature’s pain reliever

The largest use for paracetamol is for treating pain. There are many nutritional and hands-on interventions as well as exercise and stretching that work both in the short and long run to reduce pain. For example, one of the largest causes of headaches and muscle pain is the epidemic deficiency of magnesium. Magnesium is Nature’s analgesic. Magnesium is the mineral inside the center of the chlorophyll molecule. Dr. Bernard Jensen used to refer to it as “captured sunlight.” Magnesium supplementation, at the right dose, digested optimally, in the most absorbable forms, acts like a natural pain reliever and a muscle relaxant.

Magnesium deficiency epidemic. Millions of Americans are deficient in magnesium. The National Health and Nutrition Examination Survey from 2001-2008, looking at a representative sample of a bit over 18,000 Americans, found over 40% were deficient in magnesium. Dark leafy greens and foods like nuts and seeds are a great source of magnesium but most people don’t eat adequate greens let alone absorb them, and can have chronic pain because of this.  They then grab meds for their pain instead of improving their diet as well as other life-style factors like exercise and stretching.

Magnesium/acetaminophen interaction. In a trial of children with history of recurrent acute migraines, magnesium supplementation helped reduced pain. In this study it was given as pre-treatment before either the acetaminophen or ibuprofen was given. The magnesium increased the pain relieving action of the meds and shortened the duration of the headaches. They pre-treated children with magnesium before application of each med, but they didn’t try magnesium by itself, which over time might have eliminated the migraines all together.

Magnesium the marvelous

By the way, magnesium does so many more unfolding things and we learn more each day. For example, science is showing that magnesium protects the gut microbiome to help it make “feel good neurotransmitters” and help us avoid the need for anti-depressants. Magnesium is also a co-factor for over 600 enzymatic reactions in the body. Supplementation with magnesium has been shown to be beneficial in treatment of, among others, preeclampsia, migraine, depression, coronary artery disease, and asthma. The US National Health and Nutrition Survey from 2001-2006 said that magnesium intake alone contributes to vitamin D status as an independent factor . This means that the all important vitamin D we are hearing so much about, “leans” on magnesium to do some of it’s physiologic “magic.”

Magnesium in a way is like a fabulous “natural paracetamol”, but only if you digest it fully, and it takes a few days to work, not 30 minutes like popping a pill. Oh by the way, proton pump inhibitors  which are handed out like M & M’s for all types of gut issues, block the body’s use of magnesium and thereby contribute to pain syndrome incidence and the increased use of paracetamol.

Interactions. Some natural products can cause standard levels of acetaminophen to go higher in the blood stream than makes sense for the amount ingested. For example in a rat study, quercetin and chrysin were shown to increase systemic exposure to paracetamol by slowing down the metabolizing pathways. Green tea may potentiate acetaminophen, too . It may be that taking herbs and nutraceuticals can elevate blood stream levels of this analgesic and the safe dose ranges on the label can’t address these interactions .

Paracetamol for acute low-back pain. The effectiveness of U.S. pain treatments has been questioned in multiple studies. In the Lancet in 2014, a randomized, placebo controlled trial from across 235 primary care centers in Australia assessed whether the primary first recommended treatment for low back pain, paracetamol, worked or not. This is the most common use for this medication. This study had 550 patients on the med compared to 549 who were not on it. This study found that the drug didn’t help reduce pain compared to a placebo and the authors questioned the “universal endorsement” of using paracetamol for acute low-back pain.

You are not alone when it comes to pain. Over 100 million Americans are said to suffer with chronic pain. Low-back pain is a major cause of suffering and lost hours from work. So the questions surrounding safety and efficacy of pain meds, especially those which are available over the counter, are critical and affect us all.

Additional Links

References


References:
1. Roberts E, Delgado Nunes V, Buckner S, Latchem S, Constanti M,  et al. Paracetamol: not as safe as we thought? A systematic literature review of observational studies. Ann Rheum Dis. 2015 Mar 2.
2. de Vries F, Setakis E, van Staa TP, et al. Concomitant use of ibuprofen and paracetamol and the risk of major clinical safety outcomes. Br J Clin Pharmacol 2010;70:429–38.
3. Lipworth L, Friis S, Mellemkjaer L, et al. A population-based cohort study of mortality among adults prescribed paracetamol in Denmark. J Clin Epidemiol 2003;56:796–801.
4. Chan AT, Manson JE, Albert CM, et al. Nonsteroidal anti-inflammatory drugs, acetaminophen, and the risk of cardiovascular events. Circulation 2006;113:1578–87.
5. Curhan GC, Willett WC, Rosner B, et al. Frequency of analgesic use and risk of hypertension in younger women. Arch Intern Med 2002;162:2204–
6. Dedier J, Stampfer M, Hankinson S, et al. Nonnarcotic analgesic use and the risk of hypertension in US women. Hypertension 2002;40:604–8.
7.de Vries F, Setakis E, van Staa TP, et al. Concomitant use of ibuprofen and
paracetamol and the risk of major clinical safety outcomes. Br J Clin Pharmacol
2010;70:429–38.
8. Curhan GC, Willett WC, Rosner B, et al. Frequency of analgesic use and risk ofhypertension in younger women. Arch Intern Med 2002;162:2204–8
9.Evans M, Fored CM, Bellocco R, et al. Acetaminophen, aspirin and progression of advanced chronic kidney disease. Nephrol Dial Transplant. 2009 Jun;24(6):1908-18
10. Kurth T, Glynn RJ, Walker AM, et al. Analgesic use and change in kidney function
in apparently healthy men. Am J Kidney Dis 2003;42:234–44.
11. Deng X1, Song Y, Manson JE, Signorello LB, et al Magnesium, vitamin D status and mortality: results from US National Health and Nutrition Examination Survey (NHANES) 2001 to 2006 and NHANES III. BMC Med. 2013 Aug 27;11:187
12.Gallelli L1, Avenoso T, Falcone D, Effects of acetaminophen and ibuprofen in children with migraine receiving preventive treatment with magnesium. Headache. 2014 Feb;54(2):313-24
13. Winther G Pyndt Jørgensen BM, Elfving B et al Dietary magnesium deficiency alters gut microbiota and leads to depressive-like behavior. Acta Neuropsychiatr. 2015 Feb 18:1-9
14. de Baaij JH, Hoenderop JG, Bindels RJ.Magnesium in man: implications for health and disease. Physiol Rev. 2015 Jan;95(1):1-46.
15. de Baaij JH, Hoenderop JG, Bindels RJ.Magnesium in man: implications for health and disease. Physiol Rev. 2015 Jan;95(1):1-46.
16 .Salminen WF1, Yang X, Shi Q, Greenhaw J, Davis K, Ali AA. Green tea extract can potentiate acetaminophen-induced hepatotoxicity in mice. Food Chem Toxicol. 2012 May;50(5):1439-46.
17. Pingili RB, Pawar AK, Challa SR. Systemic exposure of Paracetamol (acetaminophen) was enhanced by quercetin and chrysin co-administration in Wistar rats and in vitro model: risk of liver toxicity. Drug Dev Ind Pharm. 2015 Feb 13:1-8.
18. Williams CM, Maher CG, Latimer J et al. Efficacy of paracetamol for acute low-back pain: a double-blind, randomised controlled trial. Lancet. 2014 Nov 1;384(9954):1586-96.
19. Jóźwiak-Bebenista M, Nowak JZ. Paracetamol: mechanism of action, applications and safety concern. Acta Pol Pharm. 2014 Jan-Feb;71(1):11-23.
20.   Jóźwiak-Bebenista M, Nowak JZ. Paracetamol: mechanism of action, applications and safety concern. Acta Pol Pharm. 2014 Jan-Feb;71(1):11-23.