Introduction

Dark, sticky, chewy licorice conjures up memories of childhood for many adults. Licorice makes me think of ‘trick or treating’ on cold winter nights, odd looking licorice all sort candy figures and tangy, bitter sweet sherberts.

Licorice has an unusual status in life. Reason being, it spans many categories. It is not just used in candies – it is also commonly used in the wider food industry as a flavoring and sweetener.

It features in the tobacco industry.

It is also used as a medicinal agents in both western medicine and holistic healing systems eg Traditional Chinese Medicine where it is used for a range of conditions eg to reduce inflammation, soothe mouth ulcers, heal peptic ulcers and relieve cough.

What does the scientific literature say about licorice?

What Is Licorice Root?

Licorice (also known as liquorice, sweet wood and sweet root) is harvested from a plant that is native to the Mediterranean basin and Russia. The scientific name for licorice is Glycyrrhiza glabra Fabaceae which comes from the Greek words ‘glykos’ meaning sweet and ‘rhizo’ meaning root.

In terms of sweetness, it is thought to be 50 times sweeter than sugar. Apart from sugar and carbohydrate, licorice contains very little else in terms of macronutrients, minerals and vitamins. It does contain more than 20 triterpenoids and 300 flavonoids including triterpene saponins, flavonoids, isoflavonoids and chalcones along with the glycyrrhizic acid.

I guess the high sugar content of licorice explains its role in the food industry but how about its use in health and wellness?

Let’s start with a quick review of some physiology and biochemistry.

There are three main types of steroids produced by the adrenal glands:

  • Cortisol which is the active anti-inflammatory steroid
  • Aldosterone which affects the electrolyte content of the body and blood pressure and some
  • Sex hormones (you know what they do).

Natural licorice is extracted from Glycyrrhiza glabra root which contains glycyrrhizin or glycyrrhizic acid. Glycyrrhizic acid prevents the local inactivation of cortisol. Hang in there- this is important and will all make sense.

There are two consequences to this:

Firstly, there is an increase in the level of circulating cortisol which means an increased anti-inflammatory effect in the body. Here is the twist in the tail. This effect occurs for both endogenous (or steroids made by the body) and exogenous (or prescribed steroids). This explains why cortisol is sometimes used as a ‘steroid sparing agent’ in western medicine.

This might be used in someone with chronic obstructive airways disease when the patient needs a continuous and maybe increasing dose of steroids. Some physicians might try adding licorice to boost the effects of locally produced and prescribed steroids. Need I mention, that this is not something for you to try at home. This has to be done under careful medical supervision with close monitoring.

Secondly, the excess cortisol that is hanging around essentially switches allegiance resulting in excess mineralocorticoid activity or pseudohyperaldosteronism.That means high BP and disturbance of electrolytes.

It gets even more interesting (in a geeky sort of way). There are two main forms of licorice :

  • Glycyrrhiza licorice and
  • Deglycycrriziated licorice (DGL)

The deglycycrrizinated licorice has less mineralocorticoid spill-over effects which makes it less likely to cause salt retention and electrolyte disturbance.

There are significant differences between different licorice products in the quantity, quality and even the presence of licorice (1).

There are over 8000 licorice products for sale on Amazon including candies, tea, mouthwash, toothpaste, shampoo, capsules, powder. Licorice based medication is available as an over the counter product without a prescription. There is also an intravenous formulation of licorice in some countries .

Is There Any Research?

There are 4000 publications related to licorice and almost 200 clinical trials. To put this into context, there are 599 publications and 14 clinical trials for anise which is the main imitator of licorice in the food industry.

Does Licorice Root Protect Against Heartburn and Acid Reflux?

A 2016 study from Iran evaluated the effect of adding licorice to the standard treatment of Helicobacter Pylori peptic ulcer disease. They used a randomized control trial design of 120 patients who were allocated to either standard treatment (clarithromycin, a proton pump inhibitor and amoxicillin) or standard treatment plus licorice.

The response rate in the standard group was 62% which compares to an 83% response rate in the licorice therapy arm. This difference was statistically significant (2).

Bottom Line

There is some clinical data to support a role for licorice for peptic ulcer disease.

Does It Treat Leaky Gut?

‘I have no idea’ is my official answer here. There are a grand total of 266 publications on the subject of leaky gut. Only 6 of these are clinical trials. None of these publications talk about licorice. What does that mean?

It means we don’t have a clue. Why is that? Leaky gut is a group of symptoms that are caused when the immune system reacts to germs, toxins or other substances that have been absorbed into the bloodstream via a porous (leaky) bowel.

Leaky gut is a relatively new concept in scientific medicine. Suffice it to say that it is not one of the Top 17 Sustainable Development Goals for the WHO. This means that research funders such as the National Institutes for Health, the Wellcome Trust or even the more progressive funders like the Gates Foundation are not exactly rushing out to promote earth shattering research on ‘leaky gut’.

The reality is that major funders such as these groups have a huge influence on what research is actually done (or not). I can be totally passionate about a subject but unless I have a trust fund, I can’t finance a large study without a research grant.

Bottom Line

There is no credible science linking licorice and leaky gut.

Does It Reduce Adrenal Fatigue?

There are no studies looking at adrenal fatigue and licorice. There are some (unreferenced) comments about the use of a combination of licorice with panax ginseng for adrenal fatigue.

I think that the issue here is probably the fact that there is almost nothing in the published literature about adrenal fatigue in the first place. Again adrenal fatigue is not considered to be a real entity by much of the scientific community at this stage.

Theoretically, if we consider adrenal fatigue as burn-out of the adrenal glands from overuse, then considering the fact that licorice can reduce the breakdown of cortisol which in turn directly boosts cortisol levels and indirectly acts as a mineralocorticoid mimic, then it is biologically plausible that licorice could help. Bla, bla bla. That is all theory. Unsubstantiated theory.

Here is where the basic science comes in to the picture. Deglycycrriziated licorice (DGL) is generally considered to be safer but it lacks the active ingredient for adrenal fatigue. That gives us another reason to pause before recommending licorice for adrenal fatigue. Not only is it unproven, it would be necessary to take the glycyrrhiza form of licorice which increases the chances of side effects.

A Second Look (Just To Be Sure)

The website www.Clinicaltrials.gov records ongoing research (3). Anytime that we conduct clinical research, we enter the details onto this website. This helps to coordinate research worldwide and helps to prevent duplication of research.

There are 52 studies registered on clinicaltrials.gov for licorice which means that there are 52 studies at various stages of completion. None of these studies relate to adrenal fatigue or leaky gut. That means that not only is there nothing in the published literature about adrenal fatigue, leaky gut and licorice, it means that there is nothing in the pipeline.

Bottom Line

There are no studies looking at the role of licorice for adrenal fatigue.

Does it Boost Immunity?

Despite the fact that there are papers relating to licorice and immunity, only one is relevant.

This 2006 pilot study from the National College of Naturopathic Medicine, Portland showed that glycyrrhiza herbal tinctures stimulated immune cells as quantified by CD69 expression on CD4 and CD8 T cells (4). This was a small study and involved just 7 days of observation.The study showed that licorice did increase CD69 expression on CD4 and CD8 T cells. Cool but so what? I have no idea what this means and if this is clinically relevant.

Bottom Line

There is no substantial proof that licorice boosts immunity in a clinically meaningful way.

Does It Help a Sore Throat?

There are 4 clinical studies looking at licorice for sore throats. All studies involved looking at sore throats cause by intubation and ventilation. Some general surgical procedures require full ventilation as opposed to sedation. This requires passage of a tube down the throat into the lungs to control breathing. Many patients complain of throat pain post-operatively which is caused by mechanical friction from the breathing tube.

A recent publication related to this comes from the Cleaveland Clinic where a study in 236 patients showed that pre-operative licorice gargling halved the incidence of sore throat (5). Similar findings were noted in a study carried out in India where pre-operative gargling with licorice was noted to significantly reduce the rates of sore throat ad post-operative cough (6).

The same research group in India compared the effects of licorice or candy pre-operatively in smokers and found significant reductions in sore throats and cough in this at-risk group (7).

Bottom Line

There is scientific evidence to support a role for licorice in sore throats caused by intubation and mechanical ventilation but there is no evidence to support a role for licorice in other types of sore throats eg winter colds and flus.

Can It Help Menstrual And Fertility Related Concerns?

Licorice root for fertilityThere are two clinical studies of interest here.

A 2008 study from China looked a Traditional Chinese Medicine known as Bushen Houxue for refractory polycystic ovarian disease (8). Bushen Hoxue contains consists of dodder seed 20 g, prepared rehmannia root 10 g, mulberry mistletoe 20 g, epimedium 15 g, psoralea fruit 10 g, solomonseal rhizome 10 g, honeylocust thorn 15 g, peach kernel 10 g, pleione bulbocodioides 10 g, red sage root 20 g, and licorice root 6 g.

The study used a randomized trial design and allocated 20 women to 42 cycles in the observation group and 24 women to 56 cycles in the control group. All women had received human menopausal gonadotrophin and were monitored by blood tests and monthly aspiration of their ovarian follicles.

The dose of human menopausal gonadotrophin required to induce ovulation was statistically lower in the group that received the Bushen Kouxue formula as compared to the placebo.

Pregnancy was achieved in 8 out of the 18 patients in the observation group (one twins and 7 single), with the pregnancy rate of 44.4%; while in the control group, 7 in 22 (2 twins and 5 single) was found, the pregnancy rate being 31.8%. There was no comment on the statistical significance of this difference in the abstract and the original paper was not available online.

The other problem with this study is the fact that it is impossible to select out the unique contribution of licorice over and above the effects of the other constituents in the herbal blend.

In another related study (albeit less relevant to fertility), 60 menopausal women were randomly allocated to licorice or hormone replacement therapy (HRT) in a randomized, double blind, clinical trial design (9). The participants in this trial received licorice (1140 mg/day) or HRT (a conjugated estrogen 0.312 mg/day and Medroxyprogesterone 2.5 mg/day) for 90 days.

In this study, it was observed that licorice was not very different from hormones in terms of reducing the number and duration of hot flashes, but licorice was not as good at reducing the severity of hot flashes as compared to HRT.

Bottom Line

There is no incontrovertible data showing that licorice helps with fertility.

Is Licorice Root Safe?

Licorice and licorice extract are “generally recognized as safe” (GRAS) as foods by the U.S. Food and Drug Administration.

That being said, over 93 case reports of liquorice related toxicity have been reported in the medical literature (10).

A 65 year old lady had a six month history of eating 2 to 4 boxes of Snaps licorice per day (11). This particular brand of licorice is based on a recipe from the 1930s which includes licorice granules. She presented to hospital with symptomatic hypertension and She required a seven-day hospitalization (five of which were in the ICU) until her symptoms and hypertension were controlled with a three-drug regimen.

A similar case was published but this time involved a 19 year old in Oslo (12). She too made a full recovery and kicked her licorice habit.

I am pretty sure that there is under-reporting of licorice induced hypertension as doctors may be unaware of the licorice-BP connection and many cases go unrecognised.

Two years ago, Italian pediatricians reported a case of seizures and encephalopathy in a 10 year old boy who had been eating 72 mg of glycyrrhizic acid per day for the previous 4 months (13). The astute physicians were aware of other similar case reports in the literature and made the connection.

A 50 year old lady presented to the University of Rochester in 2012 with dark urine and muscle aches (14). A diagnosis of rhabdomyolysis was made. This is a potentially life-threatening situation where muscles breakdown and release a heavy protein load which can overwhelm the kidneys. She had been consuming one and a half bags of black licorice bites containing 2% natural licorice in the prior 3 weeks.

The rhabdomyolysis was caused by the steroid effects of the licorice. And it does not end there either. The rhabdomyolysis along with the effect of licorice led to secondary hypocalcaemia, which in turn triggered secondary hyperparathyroidism. This caused even further chaos in her body biochemistry.As the title of the case report said ‘a big price for a sweet tooth’.

If you have a fondness for black licorice, the US FDA offer the following advice:

  • Avoid eating large amounts of black licorice at one time.
  • If you have been eating a lot of black licorice and have an irregular heart rhythm or muscle weakness, stop eating it immediately and contact your healthcare provider.
  • Black licorice can interact with some medications, herbs and dietary supplements. Consult a health care professional if you have questions about possible interactions with a drug or supplement you take (15).

Licorice should be avoided during pregnancy and when breastfeeding.

It should definitely be avoided during fasting as this is a time when electrolytes may be already be perturbed and licorice may worsen this further.

Finally, licorice can reduce the potency of blood thinning drugs like coumadin (warfarin).

Conclusion

As mentioned earlier, licorice has an odd status in life. It is sold as a candy but has some pretty significant side effects. I totally accept that the well-intentioned manufacturers of licorice never intended people to binge eat licorice and end up in ICU.

On the other hand, given the fact that licorice is extremely sweet, it is no wonder that people can become addicted to things like sherbert fountains (16). The FDA take this seriously and have a ‘Trick or Treat’ video on licorice that has been watched almost 100,000 times.

There is nothing about licorice that would make it a candidate for a DIY home based remedy. Firstly, there are limited data on possible benefits and secondly, it has very serious side-effects.

The best data on licorice relates to reductions in post-operative cough. It would be a terrible (possibly life-threatening) idea to try to self-medicate with licorice pre-operatively. Surgery is a major stress on that causes fluxes in hormones and electrolytes. Adding licorice to the mix (with its effects on cortisol, aldosterone, potassium and BP) could be fatal.

I think that apples sound like a much better option in my house for the ‘trick or treat’ season this year.