Is Licorice Dangerous?

The answer is NO... unless you now suffer from hypertension.

In addition, the potassium depletion rumored to be associated with licorice ingestion is also of no concern to someone taking licorice under this recovery program.

This researcher forced down 20 grams of licorice extract per day for 35 days just to see if he could deplete his potassium but failed to lower plasma levels by any significant amount. Failure to cause hypokalemia can be explain by research done in Japan in 1995. This work found that something was strangely different about the way people with licorice induced illnesses were metabolizing licorice.

Normally, glycyrrhizic acid in licorice is converted by bacteria in the intestines to 18 beta-glycyrrhetic acid before it is absorbed into the blood stream. This is done by special gut flora in a two-step process. First glycyrrhizic acid is converted to 3-Monoglucuronyl-Glycyrrhetic acid (3MGA), which is then converted to 18 beta-glycyrrhetic acid. Both are potent biologically active ingredients. In those individuals showing signs of hypokalemia, glycyrrhizic acid was hyroxyolized into 3-Monoglucuronyl-Glycyrrhetic acid (3MGA) and the metabolizing process stopped . Their gut bacteria did not continue to the second breakdown step; therefore, 3MGA was found in their plasma, not 18 beta-glycyrrhetic acid as is found in the plasma of those who do not suffer hypokalemia.

Here's what's going on: 3MGA inhibits steroid enzymes just as rapidly as 18 beta-glycyrrhetic acid so both metabolites are bioactive equals. The big difference between the two is that 3MGA remains biologically active for much longer than 18 beta-glycyrrhetic acid. Therefore, if someone with unique gut flora is taking large amounts of licorice extract daily, 3MGA can build up in the blood to high levels and completely inhibited steroid enzymes and thus cause mineralocorticoid excess and potassium depletion.

No one knows why this occurs. Researchers suspect that something in the gut flora is different which prevents the complete conversion of glycyrrhizic acid to 18-beta glycyrrhetic acid. Whatever is the cause, it is extremely rare and usually only occurs in older people.

If you want to make sure you are not one of those rare few who metabolizes licorice to 3MGA only, all you have to do, once you have acclimated yourself to taking licorice for a few weeks, is increase your dose until you notice extra edema, then stop taking licorice altogether and see how long it takes to lose the extra fluid. If you lose all the extra water you gained within 24 hours, you are metabolizing licorice to 18-beta glycyrrhetic acid and will not develop hypokalemia. If you are still puffy 24 hours after stopping licorice, you might be one of those who converts licorice to 3MGA, giving you an increased risk of developing potassium depletion. You should discontinue licorice.

But don't worry. Licorice extract is not going to seek up on you and cause problems as long as you educate yourself on how to use the herb. Fact is, when compared to the 3 million people who consumed licorice daily in the world, the number of individual cases of licorice induced hypokalemia in the literature is extremely rare. So rare that a group Japanese doctors, who searched the medical literature over the past fifty years, were only able to isolate 59 reported cases of serious illness caused by eating excessive licorice.

However, these cases have received more than ample publicity as witnessed by over 535 medical articles and letters to the editor that have discussed the 59 cases.

Not only have these 59 cases been hashed over and over and over again in the published medical literature, but well-meaning semi-professionals have allow themselves to be so swayed by the overblown bias against licorice to the point that they have mounted web-based campaigns to protect innocent people from those who suggest licorice might have an excellent benefit in recovery from certain illnesses.

Nurse Camilla Cracchiolo is the best example of someone with an obsession to inform the public about licorice dangers. Although most of what she wrote pointed out the benefits of the herb, in typical fashion and due to her strong bias, she fail to properly interpret the published material simply because so only read the abstracts, not bothering to read the full articles. Matter of fact, she has copied the abstracts to her web site in an attempt to prove her point (web site now closed). Nurse Camilla failed to mention the abstract above about the differences in gut flora and metabolism of those injured by licorice. She obviously either did not read it, or failed to understand the work.

Another web-based bias mention of licorice dangers is posted on the People Pharmacy (web site now closed). To report that a young woman developed severe headaches and lost her sex drive and menstrual periods due to excessive licorice consumption without offering any reference whatsoever is irresponsible. The same goes for saying: "As little as one ounce of natural licorice candy a day can interfere with mineral balance."

These are just examples of how negativism and bias begets more negativism and bias. Not only is the excessive number of articles about licorice dangers unwarranted, the alarming manner in which several of these unique cases were presented creates an entirely false picture and offers the rationale for understanding how level-headed people can easily allow themselves to become biased.

One example most often cited in the medical literature is reported in a Letter to the Editor of the American Journal of Psychiatry entitled, "Life-Threatening Hypokalemia Associated With Excessive Licorice Ingestion". (pubmed) In this published one-page work, two psychiatrists report on a case of licorice induced hypokalemia. There's no abstract associated with this article because abstracts don't accompany Letters to the Editor. All anyone researching licorice reads in the Pubmed data base is a scary, hair-raising title: "Life-Threatening Hypokalemia Associated With Excessive Licorice Ingestion."

The above Letter was cited hundreds of times in recent literature simply because, like Nurse Camilla, the authors believed licorice was dangerous and were looking for something scary to report. They found it in the title alone so did not bother to actually read the Letter. The title supported their bias so they just assumed someone ate too much licorice and it almost killed them!.

But the subject of the Letter was a very sick 29-year-old woman suffering from a severe case of anorexia nervosa and bulimia who was also using diuretics, and maybe using laxatives. A month before admission to the hospital, she had increased her daily consumption of licorice from her usually 300 grams/day to 600 grams/day. (Licorice is refuted to cause weight loss so it is easy to understand how anorectic people might ingest large amounts.)

As her lethargy increased, she ate more licorice and less other food and drink. She denied vomiting or laxative abuse but did admit to taking 40 mg/day of furosemide (a potent diuretic) for what she assumed was "premenstrual edema".

"Histopathologic and MRI Findings in Hypokalemic Myopathy Induced by Glycyrrhizin," is another common example of a scary title (abstract) and used by Nurse Camilla in her attempt to show how dangerous Licorice use really is. Read the article and you quickly find out that it is not about licorice at all, rather it is a report dealing with the proper use of magnetic resonance imaging equipment. It reports on the method used to imagine the muscles in the 29 year old girl above and in a 61 year old man dying of liver disease. The article is all about "T2-weighted images corresponding to the state of water retention". It concludes by suggesting that MRI is a useful non-evasive tool for follow-up procedures in muscle damage.

In 90% of the reported cases of licorice-induced illness other critical co-conditions were not made obvious in the article titles. One has to read the entire article to learn of the patient also suffered from liver failure, heart disease, anorexia, metal disorders, old age, involvement of other drugs, and etc.. Even today most doctors don't know about these other "co-conditions".

Often true for any type of investigative reading, one must pay close attention to details in order to get the whole story. The group of Japanese doctors reported that the combined use of large amounts of diuretics along with excessive use of licorice drastically increased the risk of hypokalemia in an overwhelming number of the 59 cases.

Recently, the same potent diuretic used by the 29-year-old girl with anorexia above was involved in another severe case of hypokalemia in an Italian girl also using licorice (pubmed). At least the title here is a bit more descriptive and tells the casual reader that there was a potent diuretic involved in the illness.

What does the use of diuretics really signify?

In times past, before doctors had diuretics to prescribe, consuming too much licorice induced lots of fluid retention and this obvious edema served as a warning signal. Go to a doctor's office all puffy and swollen 50 years ago and he started asking about your diet and what you had been eating lately. The doctor didn't have diuretics to give you so he continued to try to find the root cause of the fluid retention. But things changed with the use of diuretics in the 50's. If a person suffered edema from consuming too much licorice went to see a busy doctor a few years ago, the doctor might prescribe a potent diuretic to get rid of the fluid retention and the patient could then continue to ingest more licorice without a noticeable swelling and become potassium depleted! Fact is, doctors prescribing diuretics were responsible for most of the 59 cases.

Trying to warn these doctors about the dangers of licorice edema so they would not prescribe diuretics was the underlying reason why all the articles and Letters to the Editors were overly published in the medical journals.

It goes without saying that an article detailing how doctors had wrongly prescribed diuretics to treat licorice-induced edema would not have gotten past the editor's circular file.

Of course, licorice is a potent medicinal herb that can cause serious side effects if someone, not educated in its use, takes too much. And, yes, doctors and the public should be made aware of these dangers. But leaving out pertinent facts and slanting the information in such a way as to scare people who could receive great benefit from the herb is wrong!

Alcoholism and alcoholic liver disease was responsible in eight cases. Most of these occurred in France 40 years ago when a none-alcohol drink was promoted as a treatment for alcoholism. The drink was made from potent licorice extract. The alcoholics had liver disease and suffered potassium depletion even before they drink the licorice drink.

In three cases of Licorice-induced illness, severe diarrhea (lasting several weeks or more) was noted. There nothing surprising here--in many cases of hypokalemia, diarrhea alone has been found responsible.

Advanced age (65+ years) accounted for eighteen licorice induced hypokalemia cases.

It was also report that very small amounts of licorice was associated with eight cases of licorice induced illness. But this was due to congenital defect in the production of cortisol digesting enzymes.

Here's another fact! With exception of the eight found to have rare congenital enzyme defects, the rest of those who became ill ingesting licorice, ate from 100 to 200 grams of the herb per day.

Our experience suggest ~ 200 - 600 mg/day of glycyrrhizic acid as a proper dose necessary to treat most illnesses. At 90 mg of glycyrrhizic acid per gram of licorice, 400 mg equals less than five grams per day, or 1/20th of the dose found to cause illness in those who also took diuretics or suffered from some other co-condition.

In summary, 50% of the victims of mineralocorticoid excess caused by licorice were senior citizens, over 65 years old. Of the remaining, 25% were taking diuretics or laxatives. Eight percent had congenital deficiency of 11 beta-hydroxysteroid dehydrogenase and didn't not know it.

The numbers of true cases where licorice has mysteriously caused someone severe hypokalemia is reduced to two or three worldwide in the last 50 years. Two or three out of millions of daily users is not too scary when you take a close look.

Here's a few precautions to reduce your danger of developing hypokalemia to absolute zero:

1. If you have hypertension and must watch your salt consumption to keep your BP down, the chances are good that you have excessive cortisol and/or reduced levels of 11 beta-hydroxysteroid dehydrogenase. You don't need any more cortisol or any less 11 beta-hydroxysteroid; therefore, don't take licorice products.

2. Do not take diuretics or abuse laxatives when taking licorice.

3. Reduce your dose of licorice if you notice too much puffiness. A slight swelling of the ankles late in the day is a signal that you are getting enough salt-retention benefits from your current licorice so do not increase dosage.

4. Don't take licorice if you have heart problems, liver problems, kidney problems, or any other serious illness.

5. Monitor your weight and blood pressure often. Discontinue licorice if you gain excessive water-weight (retain too much fluid) or if your blood pressure increases more than 20 points above pre-licorice levels.

6. Have your electrolytes checked every few months, but do not supplement with potassium. If you are taking large doses of potassium as a preventive measure, you could masked some problem you have with licorice ingestion and potassium excretion and be lulled into a false sense of security. Potassium supplements when taking licorice extracts are NOT recommended, and are not needed unless in the rare case where something is wrong.

7. If you want to make absolutely sure you are not one of those unlucky few who metabolizes licorice to 3MGA only, all you have to do every few months (after you have already established your proper dose) is to increase your dose by 50% for several days. You should notice an increased edema. Weigh yourself late that afternoon while the increased edema is obvious, and then stop taking licorice altogether and see how long it takes to lose the extra fluid. If you lose all the extra water you gained in 24 hours, you are metabolizing licorice to 18-beta glycyrrhetic acid and will not develop hypokalemia as long as you follow the other precautions.

If you are still puffy 24 hours after stopping licorice, you might be one of those who convert licorice to 3MGA, giving you an increased risk of developing hypokalemia. You should discontinue licorice.