The Virucidal, Bactericidal and Fungicidal Effects
of Glycyrrhizin, Phyllanthus Species and Monolaurin
By Shari Lieberman, PhD, CNS, FACN
Antibiotic, antiviral and antifungal resistance has become a worldwide problem
for numerous organisms. The need for safe, effective virucidals, bactericidals
and fungicidals not subject to resistance are desperately needed. As
microorganisms become resistant to existing drugs, stronger, more toxic drugs
are often required to overcome resistance. However, over the course of time
these drugs become resistant as well. This review will focus on the promising
research that has been conducted on glycyrrhizin, Phyllanthus and monolaurin
demonstrating their broad-spectrum activity against a host of microorganisms.
Glycyrrhizin has been used in Japan for more than 20
years orally and as the intravenous drug Stronger Neo-Minophagen C (SNMC). Oral
glycyrrhizin is metabolized in the intestine to glycyrrhetinic acid (GA) and
intravenous (IV) glycyrrhizin is metabolized into glycyrrhetinic acid when
excreted through the bile into the intestines. Glycyrrhizin and glycyrrhetinic
acid exhibit similar properties and have been shown to be effective for
Hepatitis A, B, C; HIV; herpes (I, II, zoster (shingles virus), perhaps 6);
lichen planus, influenza, CMV (cytomegalovirus) and cancer. Personal experience
and reports of effectiveness show it is effective against chronic fatigue immune
deficiency syndrome (CFIDS) and the viruses associated with this condition (EBV
(Epstein-Barr) virus, CMV), condyloma (genital wart virus) and other "viral"
Glycyrrhizin has antiviral activity by inhibiting some RNA transcriptases (e.g.
HIV) and an indirect activity by decreasing cell membrane permeability (e.g.
hepatocyte injury). It inactivates viruses and inhibits viral proliferation.
Glycyrrhizin is a powerful free radical scavenger and it increases gamma
interferon, T cells and natural killer cells.
It selectively inhibits an immune system process that leads to inflammatory host
cell injury. It may enhance immune adherence responsible for immune phagocytosis
(the process by which pathogens "digest" foreign invaders) and regulation of
antibody production in protective immunity against invaders. It also inhibits a
process in the body known as the arachidonic acid cascade, which is linked to
Glycyrrhizin and Hepatitis
Hepatitis C is occurring at epidemic proportions with an estimated 3.9 million
infected in the USA, which is 4 times those infected with HIV, and 170 million
worldwide with a reported 8,000-10,000 deaths per year. Mortality is expected to
triple by 2010. It increases the risk of death from liver disease 17-fold and
increases the risk of death from liver cancer by 6-fold.6
Current treatment prognosis with interferon (INF) and antivirals provide less
than a 30 percent response rate after 1 year. Of those who exhibit viral
clearance, 30-70 percent relapse within the first few months. A sustained
response of at least 6 months occurs in 10-15 percent of patients and serious
side effects occur such as myalgia, fatigue, fever, headache, nausea, leukopenia,
thrombocytopenia, alopecia, irritability, depression, thyroid abnormalities,
pulmonary complications and retinal damage. The treatment is often worse than
the disease as many patients cannot function or work during treatment.
Interferon decreases the risk of progression to hepatocellular carcinoma only in
sustained virulogical responders. When ribavirin is used with interferon,
reports show a 28-66 percent sustained response in patients although personal
communications with infectious disease specialists reveal much poorer response
rates. The side effects of combined treatment with ribavirin are significant and
serious with an increased risk of hemolytic anemia. Pegylated interferon, in
which polyethylene glycol is added to make the interferon last longer in the
body, is given with ribavirin and adverse effects and outcome is similar to
standard therapy. The treatment is extremely expensive and unaffordable without
prescription insurance coverage.1-7
The intravenous drug form of glycyrrhizin, SNMC, is composed of monoammonium
glycyrrhizinate (as glycyrrhizin) 4 mg; aminoacetic acid 40 mg; L-cysteine HCL 2
mg; and sodium sulfite 1.6 mg per 2 ml vial. A 20 ml vial provides 40 mg
glycyrrhizin, 400 mg glycine and 20 mg L-cysteine. The therapeutic IV dose range
is 40-60 ml and as high as 100 ml. The oral therapeutic dose may be as high as
200 mg/day. SNMC has aminoacetic acid and L-cysteine added to prevent
pseudoaldosteronism, a condition resulting in sodium retention, potassium
depletion and hypertension. However, pseudoaldosteronism is rarely reported at
therapeutic doses and can be treated with spironolactone or higher intakes of
A comparative study was conducted by dividing at random 100 cases into two
groups. Group A received 100 ml SNMC per day for 3 weeks and group B received 40
ml/day for 3 weeks. The patient population consisted of: HBV (hepatitis B
virus), HCV (hepatitis C virus) and cirrhosis with 49 percent of patients
previously treated with interferon therapy showing no improvement of ALT liver
enzyme. ALT reductions (rather than viral load) are the best prognostic
predictor with respect to later development of liver cancer. Cases were rated
"markedly improved" if ALT levels dropped to less than 1.2 times normal upper
limit and "improved" if ALT levels dropped to less than 1.2-1.5 upper limit.
After intervention the results revealed that in group A, 23 of 44 cases (52.3
percent) improved and in group B, 12 of 26 cases (26.1 percent) improved. Group
A (the higher dose group) showed significant improvement compared to B (the
lower dose group).1
Another study examined collected data on hepatitis C cases treated with SNMC
followed for 15 years. Eighty-four patients received 100 ml/day of SNMC for 8
weeks, and thereafter received a maintenance dose of 2-7 times/week for 2-16
years. They were compared to 109 control patients receiving only oral
botanical/nutritional supplements. The ALT fell to normal in 35.7 percent of the
SNMC group, and 6.4 percent of the control group. After being followed for 15
years the incidence of cirrhosis was 21 percent in the SNMC group compared to 37
percent in the control group. Liver cancer incidence after 15 years was 12
percent in the SNMC group and 25 percent in the control group.2
Fifty-nine patients with chronic hepatitis C, non-responders to interferon or
those unlikely to respond to interferon were included in a study where they
either received SNMC 3 times per week or 6 times per week for a total of 4 weeks
and the results of the two groups were compared to another group receiving a
placebo. SNMC was administered either as an IV drip for 15-20 minutes (80, 160,
240 mg glycyrrhizin) or SNMC was given undiluted injected directly into a vein
in 3-5 minutes (200 mg glycyrrhizin). The proportion of patients with ALT
normalization at the end of treatment was higher in actively treated patients
than in placebo; and higher in those receiving SNMC 6 times per week (47
percent) versus 3 times per week (26 percent). Many of the patients asked for
prolongation of SNMC therapy rather than interferon because they felt better
during glycyrrhizin therapy. Since persistently high ALT greater than 80 IU/L
with chronic hepatitis C is associated with more rapid development of liver
cancer than persistently low ALT levels less than 80 IU/L, the authors suggest
oral glycyrrhizin or glycyrrhetinic acid should be for maintenance therapy.3-5
A 13-year follow up study with SNMC was conducted with chronic hepatitis C
patients. The therapeutic schedule of SNMC was aimed at suppressing ALT levels
(below 75 U/L). The patients were administered 40 ml (80 mg glycyrrhizin) of
SNMC 5-6 times per week and if ALT was lowered the maintenance therapy was 3
times per week. If this failed to lower ALT levels then SNMC was increased to
100 ml (200 mg glycyrrhizin) 5-6 times per week until patients responded. The
maintenance dose was tailored to keep ALT levels low. Liver cirrhosis occurred
significantly less frequently in 178 patients on long-term SNMC than in 100
controls (28 percent vs. 48 percent at year 13). Liver cancer developed
significantly less frequently in 84 patients on long-term SNMC than in the 109
controls (13 percent vs. 25 percent at year 15). The author notes a relationship
between the cumulative ALT score and the increase in the stage of fibrosis,
irrespective of the stage of fibrosis found in the first biopsy. To prevent
progression of fibrosis the cumulative ALT score needs to be kept increasingly
lower as the stage of fibrosis increases. Furthermore, the incidence of liver
cancer increases in parallel with the mean ALT score. Oral treatment with
glycyrrhizin and IV treatment with SNMC has been shown to significantly improve
hepatitis B with marked improvement on indices of liver function and lowering of
HbsAg (Hep B surface antigen), the levels of which are often linked to active
Glycyrrhizin and HIV
AIDS patients with high CD4/CD8 ratios (also known as helper cell/suppressor
cell ratios) improved significantly with SNMC (5 mg glycyrrhizin /kg). Almost
half the patients improved during treatment. In another study SNMC was given to
patients with haemophilia A with HIV infection who were asymptomatic.
Glycyrrhizin inhibited viral replication and had interferon-inducing,
natural-killer-cell enhancing effects. It was extremely effective in preventing
progression to AIDS and improved CD4/CD8. In vitro studies have shown that
cell-to-cell infection by HIV1, HIV-2, and T-cell lymphotropic virus type 1 is
inhibited by glycyrrhizin. Glycyrrhizin inhibits HIV replication in cultures of
cells from HIV-infected patients. In 31 percent of samples, glycyrrhizin
inhibited more than 90 percent of HIV replication. Virucidal effects include
interference with cell binding, and induction of endogenous interferon gamma.
Glycyrrhizin also affects protein kinase II and casein kinase II. Kinases
regulate many aspects that control cell growth, movement and cell death.
It also affects transcription factors, groups of proteins that read and
interpret the genetic "blueprint" in the DNA, such as activator protein 1, which
regulates gene expression in response to bacterial and viral infections, and
nuclear factor kappa B, which plays a key role in regulating the immune response
SARS and Corona Virus
No treatment for SARS (severe acute respiratory syndrome) has been established.
Glycyrrhizin inhibits SARS-associated corona virus replication and inhibits
absorption and penetration during the early steps of the replication cycle.
Glycyrrhizin is found to be most effective when given both during and after the
In vitro studies show glycyrrhizin is effective against varicellea zoster
(herpes) inactivating more than 99 percent when incubated with glycyrrhizin for
30 minutes. Glycyrrhizin demonstrates an additive effect when given with
acyclovir and beta-interferon. Herpes simplex virus 1 and 2 (HSV-1 and 2), and
Epstein Barr virus (EBV) are inactivated in vitro by glycyrrhizin.4-5
Glycyrrhizin is effective against CMV in vitro and in vivo. Liver dysfunction
improved in 4 cases and CMV disappeared after glycyrrhizin was given through IV
by the age of 12 months. In 6 infants treated with IV glycyrrhizin (10-20
mg/kg/day), liver dysfunction normalized and CMV disappeared significantly
sooner than controls. Six infants received oral glycyrrhizin at a dose of 25
mg/day (2-4 mg/kg) for 12 weeks with similar results demonstrating oral
Upper Respiratory Tract Infections
Patients with upper respiratory tract infections (URTIs) received either
glycyrrhizin or placebo in a double-blind, placebo-controlled randomized study.
Forty-one patients received 40 mL GL (SNMC) per day and 269 patients received IV
placebo. Glycyrrhizin therapy resulted in shorter hospital stay, lower-grade
fever and lower cost of therapy.7
Summary of GL Effects
Human studies showing efficacy of glycyrrhizin include: hepatitis B, hepatitis
C, HIV, upper respiratory tract infections, cytomegalovirus and SARS. In vivo
animal studies of glycyrrhizin efficacy include: influenza, herpes, encephalitis
and Candida albicans. In vitro studies of glycyrrhizin demonstrate efficacy
against hepatitis A, herpes I, II, EBV, zoster, Vaccina virus, Newcastle
disease, Vesicular stomatitis, Flaviviruses, respiratory syncytial virus, Kaposi
sarcoma-associated herpes virus and H. pylori.
Phyllanthus And Hepatitis
Researchers conducted a systematic review of 22 randomized trials for
Phyllanthus on chronic hepatitis B (HBV) infections. Combined results showed
that Phyllanthus had a positive effect on clearance of HbsAg (Hepatitis B
surface antigen). No significant difference of clearing of HBsAg, and HBV DNA
was demonstrated between Phyllanthus and interferon. There was also no
significant difference between Phyllanthus and interferon in clearing of HBeAg,
an antigen of hepatitis B virus sometimes present in the blood during acute
infection, usually disappearing afterward but sometimes persisting in chronic
disease. Phyllanthus plus interferon showed a better effect of clearance of
HBeAg and HBV DNA than interferon alone. Phyllanthus has a significant effect on
antiviral activity and was better than interferon for ALT normalization.
Phyllanthus amarus and urinaria show positive effects on HBsAg/HBeAg while only
urinaria shows a positive effect on HBV DNA.8
Twenty-five compounds from Phyllanthus were studied for in vitro effects on
hepatitis B. Niranthin, nirtetralin, hinokinin and geraniin suppressed
effectively both HBsAG and HBeAG. Niranthin showed the best anti-HBsAG activity;
hinokinin, showed the most potent anti-HBeAG activity.9
Lauric acid was discovered as the most active antiviral and antibacterial
substance in human breast milk. Monolaurin is the glycerol ester of lauric acid
and is more biologically active than lauric acid. Monolaurin has been shown to
be active against (in vitro): Influenza virus, Pneumovirus, Paramyxovirus
(Newcastle), Morbillivirus (Rubella), Coronavirus (Avian Infectious, Bronchitis
virus), herpes simplex I & II, CMV, EBV, HIV, measles, leukemia virus, Simliki
forest virus, HPV, Visna virus, Vesicular stomatitits virus, respiratory
syncytial virus, Dengue virus (type 1-4), and lymphocytic choriomeningitis. It
is effective against Gram Positive Bacteria including: Anthrax, Listeria
monocytogenes, Staphylococcus aureus, Groups A, B, F, and G streptococci,
Streptococcus agalactiae, Mycobacteria Clostridium perfringens and Gram Negative
Bacteria including: Chlamydia pneumonia, Neisseria gonorrhoeae, H. pylori,
Mycoplasma pneumonia, and Vibrio parahaemolyticus. It has also been shown to be
effective against yeast, fungi and molds including Aspergillus niger,
Saccharomyces cerevisiae, Ringworm/Tinea, Malassezia species, Penicillium
citrinum, and Candida utilis. A number of protozoa like Giardia lamblia are also
inactivated or killed by Monolaurin. Monolaurin acts by disrupting the lipid
bylayer of the virus and prevents the attachment to susceptible host cells.
Recent evidence has also indicated that it prevents replication and removes all
measurable infectivity by directly disintegrating the viral envelope making the
virus more susceptible to host defense.10
There are no known side effects of Phyllanthus or monolaurin and resistance has
not been seen with any of these natural compounds including glycyrrhizin. Blood
pressure should be monitored and a high potassium diet implemented with patients
on glycyrrhizin. There may be a synergy combining these 3 natural compounds (as
in the new formula Nutracidin™) enhancing the virucidal, bactericidal and
fungicidal effects. The effective doses may also be lower. Many patients
presenting with viral symptoms may be co-infected with bacteria and fungi (and
vice versa); therefore the broad spectrum effects of these compounds may
optimize patient outcomes.
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1. Iino S, Tango T, Matsushima T et al. Therapeutic effects of stronger neo-minopahgen
C at different doses on chronic hepatitis and liver cirrhosis. Hepatol Res.
2. Kumada H. Long-term treatment of chronic hepatitis C with glycyrrhizin
[Stronger Neo-Minophagen C (SNMC)] for preventing liver cirrhosis and
hepatocellular carcinoma. Oncol 2002;62(suppl):94-100.
3. Okuno T, Arai K, Shindo M. Efficacy of interferon combined glycyrrhizin
therapy in patients with chronic hepatitis C resistant to interferon therapy.
Nippon Rinsho. 2004;52(7): 1823-7.
4. Fiore C, Eisnhut M, Krausse R et al. Antiviral effect of Glycyrrhiza species.
Phytother Res 2008;22:141-148.
5. Numazaki K. Glycyrrhizin therapy for viral infections. African J Biotech.
6. Patrick L. Hepatitis C: Epidemiology and review of complementary/alternative
medicine treatments. Alt Med Rev. 1999;4(4):220-221.
7. Yanagawa Y, Masatsune O, Fujimoto E et al. Effects and cost of glycyrrhizin
in the treatment of upper respiratory tract infections in members of the
Japanese maritime self-defense force: preliminary report of a prospective,
randomized, double-blind, controlled, parallel-group, alternate day treatment
assignment clinical trial. Curr Ther Res. 2004;65(1):26-3.
8. Liu J, Lin H, McIntosh H. Genus Phyllanthus for chronic hepatitis B virus
infection: a systematic review. J Viral Hepat. 2001;8:358-366.
9. Huang RL, Huang YL, Chen CC et al. Screening of 25 compounds isolated from
Phyllanthus species for anti-human hepatitis B virus in vitro. Phytother Res.
10. Lieberman S, Enig MG, Preuss HG. A review of monolaurin and lauric acid:
natural virucidal and bactericidal agents. Alternative & Complementary Therapies
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