LIVER DISEASE

LICORICE ROOT:

     (More than just the candy you ate as a kid)

Remember when...

Most of us cherish childhood memories of the corner candy store where black or red licorice was sold for only 2 cents a stick. We loved it for its taste, but little did we realize that licorice is so much more than just the candy we ate as a kid.

Few herbs have been as widely used or as carefully examined over the centuries as has licorice. A member of the pea family, licorice contains a therapeutic compound known as “glycyrrhizin”, which is 50 times sweeter than sugar. The extreme sweetness of licorice makes it a real oddity, and people just love it. It is commercially used as a flavoring agent in food, tobacco, alcohol and cosmetics. But there is much more...

3,000 YEARS OF HISTORY

The earliest usage of licorice dates back over 3,000 years. It seems that the Greeks first got their hands on the sweet roots from the Scythians. Alexander the Great, Roman Emperor Caesar, and even India’s great prophet, Brahma, are on record endorsing the beneficial and valuable healing properties of licorice.

Due to its extreme sweetness, licorice was abundantly used throughout the centuries in many medicines to mask the unpleasant taste of the other ingredients. This is still a common practice in China today.

And now, modern researchers have discovered the diverse healing properties of licorice root, from its anti-inflammatory abilities to its capacity to smooth stomach upset and control coughs. Even the National Cancer Institute has investigated the medicinal benefits of licorice.

USES OF LICORICE

Most of the licorice used in medicine comes either from Europe or from China. The Chinese variety is known as “Glycyrrhiza Uralensis” (gan-cao), or sweet herb. The Chinese have had a long history of licorice use and have found at least 10 anti-inflammatory flavonoids in the root, along with an acid that has proved to be both anti-bacterial, anti-viral and anti-tussive. Its anti-inflammatory action acts like the steroid ‘cortisone’, but without cortisone’s immune-suppressing side-effects. The anti-inflammatory action of licorice is so powerful that people attempting to get off the steroid merry-go-round often use licorice to help wean their bodies off the drugs.

LICORICE IN LIVER DISEASE

A major ingredient in licorice root is called ‘glycyrrhizinic acid, or just ‘glycyrrhizin’ for short. This ingredient makes licorice a valuable herb for treating a host of liver ailments.

Licorice both protects the liver and promotes healing of this vital organ. The herb’s anti-inflammatory properties help calm hepatitis-associated liver inflammation. It also fights the virus commonly responsible for hepatitis, and supplies valuable anti-oxidant compounds that help maintain the overall health of the liver.

WHAT DO WE REALLY KNOW ABOUT LICORICE ROOT?

    (The Scientific Research Behind the Herb)

In recent years, researchers have examined the effects of licorice root used traditionally by herbalists to support liver function and to treat diseases of the liver. In most cases, clinical research has confirmed this traditional experience and wisdom by discovering the mechanisms and modes of action by which licorice exerts its therapeutic effects.

Known as the “Grandfather of Herbs”, licorice, (and especially glycyrrhizin, its major extract), are backed by a multitude of clinical research and double-blind scientific studies that support their positive and direct protective effects on the liver.

We now know that:

LICORICE ROOT EXTRACT (GLYCYRRHIZIN)--- LOWERS LIVER ENZYME LEVELS.

In the American Journal of Gastroenterology, 2001, Van Rossum TG and collaborators evaluated the short term effect of glycyrrhizin extract from licorice root on serum ALT in European patients. Results indicated a significant reduction in ALT liver enzymes in patients with chronic hepatitis C. [1]

In a multi-center double-blind study performed in Japan (Oncology, 2002) ALT enzyme levels decreased in patients receiving a licorice preparation known as ‘stronger neo-minophagen c (SNMC). Results indicated that glycyrrhizin treatment was particularly helpful in patients with chronic hepatitis C who failed to respond to interferon and in those who could not be treated with interferon for various reasons. [2]

These findings were supported by several other investigators including: Suzuki et al (1983), who confirmed licorice’s ability to suppress ALT in patients with chronic hepatitis in a randomized double-blind controlled trial of 133 patients; Hino L, et al (1986) and Yasuda et al (2001) who proved snmc licorice preparation to be useful in the improvement of transaminase and liver histology. [3-5]

In a further study, eighty patients with hepatitis, 40 acute and 40 chronic, were given oral glycyrrhizin or placebo. In the glycyrrhizin group, all indicators of liver function returned to normal in 85 percent of subjects with acute hepatitis within 30 days, compared to 35 percent in the control group. In patients with chronic hepatitis, 75 percent experienced normalization of liver function, versus 10 percent in the control group. Su XS, et al [7]

LICORICE ROOT EXTRACT LOWERS LIVER CANCER RATES IN HEP C PATIENTS

In Arase and collaborators (1997), the authors investigated the long term effect of glycyrrhizin on hepatic cancer rates in patients with chronic HCV. In this study, liver cancer rates of 84 patients who underwent long term glycyrrhizin treatment were significantly lower than in the 109 patients who were not treated with glycyrrhizin. [6]

At Toranomon Hospital, Okinaka, Memorial Institute for Medical Research in Tokyo, Japan (J. Gastroenterology, 2002), a retrospective study to evaluate the long-term preventive effect of glycyrrhizin on hepatocellular carcinoma development showed that the therapy was effective in lowering the ALT value and in preventing liver cancer. [8]

MECHANISMS OF HEPATOPROTECTION:     >> Further Clinical Studies <<

The mechanisms of hepatoprotection of the liver by licorice are diverse. They include:

• anti-oxidant activity of glycyrrhizin - Kiso et al (1984); Abdugafurova et al (1990); Ju et al (1989). [9-11]
• direct anti-viral effects - Hikino (1988) ; Crance (1990). [12-13]
• enhancement of interferon production - Shinada (1986). [14]
• enhancement of interleukin and T-Cell activity in the liver - Abe, M (2003); Kimura (1992). [15-16]
• direct anti-inflammatory effects - Abe, (2003); Fujisawa Y, (2000). [15, 17]
• anti-cancer effects - Wang (2001). [19]

ORAL EFFECTIVE DOSE

Oral administration of glycyrrhizin alone or as licorice root extract has been tested in mice (Ozaki et. al; Wang Z et al) and found to be comparable, with each form achieving similar levels of glycyrrhizin in the plasma [18, 20]

SUMMARY

Licorice is the most frequently used herb in Traditional Chinese Medicine and has been extensively studied. It is a sweet, mild herb and has many functions. Numerous scientific studies support its value in hepatitis and liver disease.

It exhibits anti-viral effects and can inhibit virus proliferation. It can normalize liver ALT and AST enzymes and restore liver function from damage due to carbon tetrachloride. Licorice can reduce degeneration and necrosis, promote regeneration of liver cells, and inhibit fibrosis.

Licorice is the most broad-spectrum natural detoxifying agent known, ridding the body of over 1200 different toxins. It is often used as an anti-inflammatory agent because it contains chemical components (i.e. glycyrrhizin) that act similarly to cortisone, but without the side effects.

Licorice root is rich in flavonoids, amino acids and biotin. As a tea, it acts as an anti-tussive (anti-cough) action similar to codeine, but without the drowsiness. It is safe in a carefully prepared formulation. Since the herb is powerful, only small doses are usually sufficient to achieve excellent results.

Many Chinese formulas use licorice as a harmonizing ingredient. It is believed that licorice harmonizes the ingredients in an herbal formulation, eliminating harshness of action and promoting smooth activity of the herbs.

WHAT YOU DIDN’T WANT TO HEAR:

(The downside of licorice)

Licorice is generally a very safe herb when consumed in small amounts. The United States Food and Drug Administration (FDA) has rated licorice as “generally recognized as safe” (GRAS) [[Code of Federal Regulations] [Title 21, Volume 3] [Revised as of April 1, 2004] [CITE: 21CFR184.1408] as an additive to most foods. However, when consumed in large amounts, licorice can exhibit side-effects in certain individuals.

Remember those licorice sticks you ate as a child? Those candies contain a very high amount of glycyrrhizic acid that can increase the sodium content of blood, thereby gradually increasing blood pressure. This can also cause a loss of potassium (hypokalemia) that can react with certain medication you may be taking.

Also, certain people lack a type of bacteria in their gut that is needed to breakdown licorice. If they ingest large amounts of licorice extract daily, the by-products of licorice metabolism can build up in their blood to high levels. This can also result in water retention, potassium loss and increased blood pressure. No one knows why this occurs. Researchers suspect that something in the gut flora is different in these people that prevents the complete breakdown of licorice in their bodies. Fortunately, the number of people lacking this type of bacteria is quite small.

HOW MUCH GLYCYRRHIZIN IN LICORICE IS TOO MUCH?

Several scientific studies have been performed to determine the minimum dosage of glycyrrhizin extract (derived from licorice) required to raise blood pressure in a normal individual. This is known as the “no effect on hypertension.”

In one such scientific experiment by Van Gelderen and associates, doses of 0,1,2, and 4mg of glycyrrhizin (GA) extract per kilogram of body weight were administered orally to 39 healthy female volunteers for 12 weeks . Females in the 4mg/kg group experienced a ‘slight rise’ in blood pressure after this time. The author’s concluded that a “no effect level” of 2mg/kg would not cause a rise in blood pressure. This “no effect level” corresponds to 120 mg of glycyrrhizinic acid (glycyrrhizin) in a 60 kg (132 pound) woman. [21]

In a further study consisting of a review of published reports on licorice, (Stormer, FC, et al) it was observed that : “for the most sensitive individuals, a regular daily intake of more than about 100 mg of glycyrrhizic acid (derived from licorice roots) seems to be enough to produce adverse effects. Most individuals, who consume 400 mg of glycyrrhizic acid daily, experience adverse effects.” [22]

So there appears to be a consensus that consuming fewer than 100mg to120 mg a day of glycyrrhizin extract from licorice root is safe for most healthy adults. As a further protective measure, it has been suggested by some that the above dosage of 120mg be further reduced by a safety factor of 50%. This would mean dividing 120mg a day in half. Those who advocate using only 60 mg of glycyrrhizin (one half of the 120 mg found safe in the Van Gelderen study), further suggest that this amount should then prove safe for everyone (even those who might be sensitive to licorice effects). Other researchers have gone so far as to suggest using only 20% or even 10% of the Van Gelderen study as a safety margin for everyone. This would equate to between 12 mg and 24 mg of glycyrrhizin from licorice root per day.

Generally, licorice roots contain variable amounts of glycyrrhizin extract, with typical figures in the range of 4% for Chinese licorice roots. The German Commission E monograph on licorice, (Blumenthal, M [editor] ) also defines the glycyrrhizin content of licorice root at 4%. Using 60 mg (half of the recommended 120 mg) of glycyrrhizin as the maximum allowable amount based on the above estimates, regular ingestion of licorice root would be limited to about 2 grams (2,000mg) of the raw herb per day. [23]

HOW MUCH GLYCYRRHIZIN EXTRACT IS IN NU-LIVER PC?

Definitions:

1. Licorice Root: the entire raw herb containing several ingredients
2. Glycyrrhizin Extract: the major ingredient found in Licorice Root

Nu-Liver PC contains 20 mg of a 5:1 concentration of licorice root in each capsule. This is equivalent to 100 mg of the raw licorice herb in decoction (after the herb is boiled and powdered). Since Chinese licorice root contains approximately 4% of glycyrrhizin extract, one capsule of Nu-Liver PC would contain approximately 4 mg of glycyrrhizin.

The daily dose of 1 capsule of Nu-Liver PC taken 3 times a day contains approximately 12 mg of glycyrrhizin, a dose well BELOW the 50 to 60 mg safety margin established by the scientific journals as ‘safe for even those who might be sensitive to licorice.’

WHY ADD GLYCINE TO NU-LIVER PC?

We have also added glycine to our Nu-Liver PC formulation. Glycine is an amino acid normally used by the body to help the liver in detoxification of compounds and for the synthesis of bile acids. However, based on the original Russian trials, scientific data compiled from clinical experiments using glycine clearly show that adding glycine can also help to prevent the development of hypertension and protect the body from a rise in blood pressure potentially caused by increased amounts of glycyrrhizin. [24-28]

LABEL WARNING

Regardless of the results of all these scientific studies, and even with a built-in safety margin of 50%, 20% or even 10% of the recommended dosage of licorice, Nu-Liver PC will carry the following recommendation on each bottle:

• If pregnant, lactating, have high blood pressure, or taking medication, consult a healthcare practitioner before using this product.

FINAL THOUGHTS:

Modern society has inherited knowledge about the herbal treatment of liver disease from many cultures. The dominant Western medical culture has largely ignored this knowledge until recently. Research into licorice, traditionally used in the treatment of liver disease, has significantly advanced in the past 15 years, and much of what has now been scientifically discovered supports traditional knowledge.

GO TO BUY NU-LIVER PC --- click here*****

REFERENCES

(Click on the author(s) for more information)

1. Van Rossum TG, Vulto AG, Hop WC, Schalm SW. Glycyrrhizin-induced reduction of ALT in European patients with chronic hepatitis C. Am J Gastroenterol. 2001 Aug; 96(8):2432-7.
2. Kumada H. Long-term treatment of chronic hepatitis C with glycyrrhizin [stronger neo-minophagen C (SNMC)] for preventing liver cirrhosis and hepatocellular carcinoma. Oncology. 2002;62 Suppl  1:94-100.
3. Suzuki H, Ohta T, Takino T, Fujisawa K, Hirayama C. Effects of glycyrrhizin on biochemical tests in patients with chronic hepatitis. Double-blind trial. Asian Med J 1983; 26:423-38 [NO ABSTRACT]
4. Hino L, Miyakawa H, Takahashi J, Kumada H, Ikeda K, Yoshiba A, et al. Effect of large dose of SNMC on the liver histology of chronic active hepatitis. Kan- Tansui 1986; 12: 797 [NO ABSTRACT]
5. Iino S, Tango T, Matsushima T, Toda G, Miyake K, Hino K, Kumada H, Yasuda K, Kuroki T, Hirayama C, Suzuki H. Therapeutic effects of stronger neo-minophagen C at different doses on chronic hepatitis and liver cirrhosis. Hepatol Res. 2001 Jan 1;19(1):31-40.
6. Arase Y, Ikeda K, Murashima N, Chayama K, Tsubota A, Koida I, Suzuki Y, Saitoh S, Kobayashi M, Kumada H. The long term efficacy of glycyrrhizin in chronic hepatitis C patients. Cancer. 1997 Apr 15; 79(8):1494-500.
7. Su XS, Chen HM, Wang LH, Jiang CF, Liu JH, Zhao MQ, Ma XH, Zhao YC, Han DW. Clinical and laboratory observation on the effect of glycyrrhizin in acute and chronic viral hepatitis. J Tradit Chin Med. 1984 Jun;4(2):127-32.
8. Chayama K. Management of chronic hepatitis C and prevention of hepatocellular carcinoma. J Gastroenterol. 2002; 37 Suppl 13:69-73.
9. Kiso Y, Tohkin M, Hikino H, Hattori M, Sakamoto T, Namba T. Mechanism of antihepatotoxic activity of glycyrrhizin. I: Effect on free radical generation and lipid peroxidation. Planta Med. 1984 Aug;50(4):298-302.
10. Abdugafurova MA, Li VS, Sherstnev MP, Atanaev TB, Isamukhamedov ASh, Bachmanova GI. Antioxidative properties of glycyrrhyzic acid salts and their effect on the liver monooxygenase system. Vopr Med Khim. 1990 Sep-Oct;36(5):29-31.
11. Ju HS, Li XJ, Zhao BL, Han ZW, Xin WJ. Effects of glycyrrhiza flavonoid on lipid peroxidation and active oxygen radicals. Yao Xue Xue Bao. 1989;24(11):807-12.
12. Hikino. "Natural products for liver diseases" 1988 Economic and Medicinal Plant Research Volume 2 (39-67). [NO ABSTRACT]
13. Crance JM, Biziagos E, Passagot J, van Cuyck-Gandre H, Deloince R. Inhibition of hepatitis A virus replication in vitro by antiviral compounds. J Med Virol. 1990 Jun;31(2):155-60.
14. Shinada M, Azuma M, Kawai H, Sazaki K, Yoshida I, Yoshida T, Suzutani T, Sakuma T. Enhancement of interferon-gamma production in glycyrrhizin-treated human peripheral lymphocytes in response to concanavalin A and to surface antigen of hepatitis B virus. Proc Soc Exp Biol Med. 1986 Feb;181(2):205-10.
15. Abe M, Akbar F, Hasebe A, Horiike N, Onji M. Glycyrrhizin enhances interleukin-10 production by liver dendritic cells in mice with hepatitis. J Gastroenterol. 2003; 38(10):962-7. [NO ABSTRACT]
16. Kimura M, Watanabe H, Abo T. Selective activation of extrathymic T cells in the liver by glycyrrhizin. Biotherapy. 1992;5(3):167-76.
17. Fujisawa Y, Sakamoto M, Matsushita M, Fujita T, Nishioka K. Glycyrrhizin inhibits the lytic pathway of complement--possible mechanism of its anti-inflammatory effect on liver cells in viral hepatitis. Microbiol Immunol. 2000; 44(9):799-804.
18. Ozaki Y, Noguchi M, Kamakura H, Harada M. Studies on concentration of glycyrrhizin in plasma and its absorption after oral administration of licorice extract and glycyrrhizin. Yakugaku Zasshi. 1990 Jan;110(1):77-81.
19. Wang ZY, Nixon DW. Licorice and cancer. Nutr Cancer. 2001;39(1):1-11.
20. Wang Z, Nishioka M, Kurosaki Y, Nakayama T, Kimura T. Gastrointestinal absorption characteristics of glycyrrhizin from glycyrrhiza extract. Biol Pharm Bull. 1995 Sep;18(9):1238-41.
21. van Gelderen CE, Bijlsma JA, van Dokkum W, Savelkoul TJ. Hum Exp Toxicol. 2000 Aug;19(8):434-9.
22. Stormer FC, Reistad R, Alexander J. Food Chem Toxicol. 1993 Apr;31(4):303-12.
23. Blumenthal, M [editor] :The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin, Texas: American Botanical Council, 1998.] [NO ABSTRACT]
24. Jackson AA, Dunn RL, Marchand MC, Langley-Evans SC. Increased systolic blood pressure in rats induced by a maternal low-protein diet is reversed by dietary supplementation with glycine. Clin Sci (Lond). 2002 Dec;103(6):633-9.
25. Quan H, Athirakul K, Wetsel WC, Torres GE, Stevens R, Chen YT, Coffman TM, Caron MG. Hypertension and impaired glycine handling in mice lacking the orphan transporter XT2. Mol Cell Biol. 2004 May;24(10):4166-73.
26. Yamada K, Moriguchi A, Mikami H, Okuda N, Higaki J, Ogihara T. The effect of central amino acid neurotransmitters on the antihypertensive response to angiotensin blockade in spontaneous hypertension. J Hypertens. 1995 Dec;13(12 Pt 2):1624-30.
27. Hafidi ME, Perez I, Zamora J, Soto V, Carvajal-Sandoval G, Banos G. Glycine intake decreases plasma free fatty acids, adipose cell size, and blood pressure in sucrose-fed rats. Am J Physiol Regul Integr Comp Physiol. 2004 Dec;287(6):R1387-93. Epub 2004 Aug 26.
28. Quan H, Athirakul K, Wetsel WC, Torres GE, Stevens R, Chen YT, Coffman TM, Caron MG. Hypertension and impaired glycine handling in mice lacking the orphan transporter XT2. Mol Cell Biol. 2004 May;24(10):4166-73.

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