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Abstract

L-Lysine is an essential amino acid that has to be available in sufficient amounts in feed-stuffs to meet the nutri-tional requirements of animals and humans. This supplementation is realized by the direct addition of Lysine and, as a result, a tremendous growth in the market has taken place in the past ten years. L-Lysine is a necessary build-ing block for all proteins in the body. L-Lysine plays a major role in calcium absorption, building muscle protein, recovering from surgery or sports injuries and the body's production of hormones, enzymes, and antibodies. This review describes the clinical significance of L-Lysine in the treatment of various pathological conditions like herpes simplex virus (HSV) infection, osteoporosis, anxiety and mood disturbances, migraine etc. Clinical studies produc-ing contradictory results on the effects of oral L-Lysine supplementation as prophylaxis or treatment of herpes simplex virus infections have been discussed in detail. This review also discusses the safety profile and scientific rational behind the alleged physiological benefits of its tremendous increase in its uses in the intervention of drug therapies like in Alzheimer's dementia, hair loss, shingles, cancer, cardiovascular diseases and aging. The benefits of using L-Lysine as a diet supplement in relation to future prospective are also covered.
Meenu Singh et al., Int. J. Res. Pharm. Sci., 2(4), 2011, 637-642
©JK Welfare & Pharmascope Foundation | International Journal of Research in Pharmaceutical Sciences 637
Medicinal Uses of L-Lysine: Past and Future
Meenu Singh*
1
, D. Muralidhara Rao
2
, Shivansh Pande
3
, Sowjanya Battu
4
, Mahalakshmi. K
4
, K. Rajeswar Dutt
4
,
M. Ramesh
5
1
Department of Pharmacy, NIMS University, Shobha nagar, Jaipur- 303121, Rajasthan, India
2
Dept. of Biotechnology, S. K. University, Anantapur, Andhra Pradesh, India
3
Apollo Hospitals, Jubilee Hills, Hyderabad, Andhra Pradesh, India
4
CMR college of Pharmacy, Medchal Road, Hyderabad-501401, Andhra Pradesh, India
5
Department of Biotechnology, JNTUK, Kakinada, Andhra Pradesh, India
ABSTRACT
L-Lysine is an essential amino acid that has to be available in sufficient amounts in feed-stuffs to meet the nutri-
tional requirements of animals and humans. This supplementation is realized by the direct addition of Lysine and,
as a result, a tremendous growth in the market has taken place in the past ten years. L-Lysine is a necessary build-
ing block for all proteins in the body. L-Lysine plays a major role in calcium absorption, building muscle protein,
recovering from surgery or sports injuries and the body's production of hormones, enzymes, and antibodies. This
review describes the clinical significance of L-Lysine in the treatment of various pathological conditions like herpes
simplex virus (HSV) infection, osteoporosis, anxiety and mood disturbances, migraine etc. Clinical studies produc-
ing contradictory results on the effects of oral L-Lysine supplementation as prophylaxis or treatment of herpes
simplex virus infections have been discussed in detail. This review also discusses the safety profile and scientific
rational behind the alleged physiological benefits of its tremendous increase in its uses in the intervention of drug
therapies like in Alzheimer's dementia, hair loss, shingles, cancer, cardiovascular diseases and aging. The benefits
of using L-Lysine as a diet supplement in relation to future prospective are also covered.
Keywords: L-Lysine; Herpes simplex virus (HSV); Migraine and Osteoporosis.
INTRODUCTION
L- Lysine is an essential amino acid in human nutrition,
meaning the body cannot produce it, therefore, it must
be obtained through diet or supplementation (Buda-
vari S, 1989). Lysine was first isolated from casein (a
milk phosphoprotein) in 1889 by the German dentist
Heinrich Drechsel (Dorland, 1965). It was first intro-
duced in the US market as Lysine hydrochloride in 1955
(Flodin NW, 1997). There was an interest in fortifying
bread with Lysine to target populations with Lysine-
poor diets. However, the US Food and Drug Admini-
stration refused to modify the standards of identity for
white bread (L-Lysine. Monograph, 2007 and Flodin
NW, 1997). It is estimated that more than 600,000
metric tons of Lysine are produced annually and, owing
to the exploitation of new uses in pharmaceuticals,
cosmetics and polymer materials, the market shows a
growth potential of 710% per year (Mattheos Koffas
and Gregory Stephanopoulos, 2005). Lysine is impor-
tant for proper growth, and it plays an essential role in
the production of carnitine, a nutrient responsible for
converting fatty acids into energy and helping to lower
cholesterol. One of the key building blocks of muscle
tissue, this amino acid is commonly used by athletes to
support lean mass building and the overall health of
muscle and bone.
CLINICAL SIGNIFICANCE OF L-LYSINE
Potential Role in Herpes Simplex Virus (HSV) Infection
According to University of Maryland Medical Centre
(UMM), it indicates that lysine taken regularly prevent
from developing cold sores and genital herpes. Studies
have been mixed, yielding both positive and negative
results, and more are required to establish any benefit.
In the year 1978, Griffith RS et al., had done a multi-
centered study of lysine therapy in herpes simplex in-
fection and found a beneficial effect from supplemen-
tary lysine in accelerating recovery from herpes sim-
plex infection and suppressing recurrence. Tissue cul-
ture studies have demonstrated an enhancing effect on
viral replication when the amino acid ratio of arginine
to Lysine favours arginine. The opposite, preponder-
ance of lysine to arginine, suppresses viral replication
and inhibits cytopathogenicity of herpes simplex virus.
The codons characterizing herpes simplex DNA appar-
ently specify production of viral capsids at the expense
of host cell histones (Griffith RS et al., 1978). Other
study in the year 1980, followed 65 individuals, found
www.ijrps.pharmascope.org
ISSN: 0975-7538
Review Article
* Corresponding Author
Email: meenupharma@gmail.com
Contact: +91-8099334083
Received on: 24-09-2011
Revised on: 02-10-2011
Accepted on: 02-10-2011
Meenu Singh et al., Int. J. Res. Pharm. Sci., 2(4), 2011, 637-642
638 ©JK Welfare & Pharmascope Foundation | International Journal of Research in Pharmaceutical Sciences
no benefit but they used lower dosages of lysine (Mil-
man N et al., 1980). In 1984, McCune MA et al., inves-
tigated the treatment of recurrent herpes simplex in-
fections with L-lysine monohydrochloride in a random-
ized, double-blind, placebo-controlled, cross-over
study of forty-one patients and found that oral inges-
tion of 1,248 mg a day of L-Lysine monohydrochloride
shows evidence of decreasing the recurrence rate of
herpes simplex attacks in non immunocompromised
hosts. A dose of 624 mg a day was not effective. L-
Lysine may also be capable of decreasing the severity
of symptoms associated with recurrences. Neither
dosage showed any evidence of shortening the healing
time compared to placebo (McCune MA et al., 1984).
In 1987, Griffith RS et al. had studied the treatment
and prophylaxis of L-Lysine in frequently recurrent
herpes simplex infection in a double-blind, placebo-
controlled, multicenter trial of oral L-Lysine monohy-
drochloride for the prevention and treatment of recur-
rent herpes simplex (HSV) infection was conducted.
The treatment group was given L-Lysine monohydro-
chloride tablets (1,000 mg L-lysine per dose) 3 times a
day for 6 months. A total of 27 (6 male and 21 female)
subjects on L-Lysine and 25 (6 male and 19 female)
subjects on placebo completed the trial. The L-Lysine
treatment group had an average of 2.4 percent less
HSV infections, symptoms were significantly dimin-
ished in severity and healing time was significantly re-
duced. L-Lysine appears to be an effective agent for
reduction of occurrence, severity and healing time for
recurrent HSV infection (Griffith RS et al., 1987). In a
report, researchers describe a relationship between
lysine and herpes simplex virus (HSV), the amino acid
arginine's composition is high in the HSV viral coding
thus, replication of the virus requires high consumption
of arginine. Lysine appears to be an “antimetabolite,”
acting as an analogue of arginine, competing for ab-
sorption and entrance into tissue and cells. Lysine in-
hibits HSV replication by limiting arginine (by compet-
ing with it) during viral replication. Both cold sores and
genital herpes are also caused by a virus called herpes
simplex. After infection, this virus hides in certain
nerve cells and re-emerges under times of stress. Test
tube research suggests that lysine fights this virus by
blocking arginine, an amino acid the virus needs in or-
der to replicate (Griffith RS et al., 1981). For this rea-
son, lysine might be most effective when used in con-
junction with a low-arginine diet. However, this widely
stated claim has not been proven.
When taken in sufficient doses, it appears that regular
use of lysine supplements might be able to reduce the
number and intensity of herpes flare-ups (Flodin NW,
1997). One double-blind, placebo-controlled study fol-
lowed 52 participants with a history of herpes flare-ups
(Griffith RS et al., 1987). While receiving 3 g of L-lysine
every day for 6 months, the treatment group experi-
enced an average of 2.4 fewer herpes flare-ups than
the placebo groupa significant difference. The lysine
group's flare-ups were also significantly less severe and
healed faster. Lysine prophylaxis was 100% effective in
preventing herpetic labialis in patients suffering from
frequent lesion occurrence. Treatment for recurrent
aphthous ulcers (RAU; acute painful oral ulcers, “can-
ker sores”) was also evaluated in this study. Only 1 of
28 patients did not benefit from lysine therapy. Dosing
was 500 mg lysine/day for prevention and 1000 mg
every 6 hours upon development of prodrome in both
treatments. (Wright E, 1994).
Potential Role in Osteoporosis
Osteoporosis is a bone disorder in which the bones
become weak and brittle particularly in the hips, spine
and wrists and increases the risk of falls or fractures.
The ability of L-Lysine to encourage calcium absorption
may help guard against osteoporosis-related bone loss.
L-Lysine plays a role in maintaining healthy bones be-
cause it helps our body absorb calcium, while reducing
the quantity of calcium that we lose in our urine. Ac-
cording to the University of Maryland Medical Centre
(UMM), laboratory research suggests that L-Lysine,
used in combination with L-Arginine, boosts the activ-
ity of bone-forming cells and increases collagen pro-
duction. This can help contribute to increased bone
strength. Therefore, Lysine may be associated with
protection against osteoporosis (Fini M et al., 2001).
However, there are no research studies to link Lysine
with osteoporosis prevention in humans (University of
Maryland Medical Centre, Lysine, 2010). Calcium defi-
ciency contributes to age-related bone loss, conse-
quently, any preventive approach to osteoporosis
should include dietary Ca
++
adjustment or supplemen-
tation.
The ideal Ca
++
supplement would yield the greatest
bioavailability. Studies in animals have shown that die-
tary supplements with certain amino acids, particularly
L-lysine, can increase Ca
++
absorption. In one study, the
acute effects of an oral Ca
++
load (3 g as CaCl
2
) adminis-
tered with or without 400 mg of L-lysine were com-
pared in 15 healthy and 15 osteoporotic women. In all
cases, the oral Ca
++
load determined a progressive in-
crease in serum total Ca
++
and a concomitant decrease
in neophrogenous c-AMP. As expected, a progressive
increase in urinary Ca
++
excretion was also observed,
except in the L-Lysine-treated healthy subjects, who
exhibited a blunted calciuric response to the Ca
++
load.
In a second study, the effects of a short-term dietary
supplementation with L-Lysine, L-Valine, or L-
Tryptophan (800 mg/day) on 47C Ca
++
fraction absorp-
tion were compared in 45 osteoporotic patients. L-
Lysine but not L-Valine or L-Tryptophan significantly
increased the intestinal absorption of the mineral
(Civitelli R et al., 1992).
Potential Role in Anxiety and Mood Disturbances
L-Lysine has a known anxiolytic action through its ef-
fects on serotonin receptors in the intestinal tract. One
study on rats showed that overstimulation of the 5-HT
4
Meenu Singh et al., Int. J. Res. Pharm. Sci., 2(4), 2011, 637-642
©JK Welfare & Pharmascope Foundation | International Journal of Research in Pharmaceutical Sciences 639
receptors in the gut is associated with anxiety-induced
intestinal pathology (Smriga and Torii, 2003). L-Lysine,
acting as a serotonin antagonist and therefore reducing
the overactivity of these receptors, reduced signs of
anxiety and anxiety-induced diarrhoea in the sample
population. Another study showed that lysine defi-
ciency leads to a pathological increase in serotonin in
the amygdala, a brain structure that is involved in emo-
tional regulation and the stress response (Smriga et al.,
2002). L-Lysine appears to diminish long-term anxiety
in individuals who fail to get an adequate amount L-
Lysine in their diet. Human studies have also shown
negative correlations between reduced Lysine intake
and anxiety. A population-based study in Syria included
93 families whose diet is primarily grain-based and
therefore likely to be deficient in Lysine. Fortification of
grains with Lysine was shown to reduce markers of
anxiety, including cortisol levels, and also led to poten-
tiation of benzodiazepine receptors (Smriga et al.,
2004). According to a randomised, double-blind trial,
fortification of Lysine in a wheat-based (L-Lysine defi-
cient) diet significantly reduced anxiety score in males,
but not females with high baseline anxiety. It is sus-
pected that L-lysine’s action as a 5-HT
4
receptor an-
tagonist and benzodiazepine receptor agonist are re-
sponsible for the observed effect. In contrast, a pro-
spective study of 29 133 men (aged 50-69 years) found
no association between L-Lysine intake and depressed
mood. A study performed in the year 2007 concluded
that L-Lysine when combined with the amino acid L-
Arginine appears to relieve mental stress and anxiety
(Smriga M et al., 2007).
Due to lack of sufficient data it is difficult to predict the
use of L-Lysine in the treatment of anxiety and mood
disturbances hence further studies are required in this
field to understand the mechanism and to provide firm
evidence for its uses as antianxiety agent.
Potential Role in Migraine
The process of inflammation is crucial in migraine, and
several non steroidal anti inflammatory drugs (NSAIDs)
are effective in the treatment of migraine attacks. De-
spite their efficacy, the routine use of NSAIDs is limited
by side effects as well as incomplete efficacy in some
patients. Lysine acetylsalicylate is a form of aspirin, a
chemical with pain-relieving properties (Krymchan-
towski A V, 2005). In April 2011, the journal "Neurol-
ogy" published the findings of a study that measured
the effectiveness of lysine acetylsalicylate against se-
vere headaches. The researchers start by acknowledg-
ing the well-established fact in the scientific commu-
nity that this substance alleviates the usual acute mi-
graine attack. The study concludes that lysine acetyl-
salicylate is also powerful against strong headaches
brought on by chemical withdrawal (W. Weatherall et
al., 2010). Lysine clonixinate is a nonsteroidal anti-
inflammatory drug. Some of its formulation comes
from nicotinic acid: niacin, or vitamin B
3
. In 2001, the
Brazilian journal "Arquivos de Neuro-Psiquiatria" --
"Archives of Neuropsychiatry" -- reported on research
that examined whether lysine clonixinate relieved
acute migraine. The substance relieved moderate mi-
graine pain within one to four hours of administration
of the drug at a better rate than the placebo used. Re-
garding its performance against severe migraine, lysine
clonixinate also relieved pain, but at the same rate of
success as the placebo. On comparison of the combina-
tion of lysine acetylsalicylate (equivalent to 900 mg
aspirin) and 10 mg metoclopramide (LAS+MTC) with
oral sumatriptan (100 mg) and placebo in 421 patients
with migraine. LAS+MTC was as effective as sumatrip-
tan with a decrease of headache from severe or mod-
erate to mild or none of 57% and 53%, respectively, for
the first migraine attack treated. Both treatments were
better than placebo (success rate 24%). LAS+MTC were
significantly more effective in the treatment of nausea
than sumatriptan and was better tolerated (adverse
events in 18% and 28%). LAS+MTC are as effective as
sumatriptan in the treatment of migraine attacks. It is
also much cheaper (P Tfelt-Hansen et al., 1995).
OTHER SIGNIFICANT EFFECTS
Alzheimer's dementia (AD)
There is a growing body of evidence that implicates the
herpes simplex type 1 virus (HSV-1) in the development
of Alzheimer's dementia (AD). HSV-1 has been found to
be present in the cerebrum of the great majority of
older adults, and in many of the same areas of the
brain that are affected by AD. When active, the virus
may contribute to the formation of the neuro-fibrillary
tangles and amyloid plaques characteristic of AD. Like
AD, HSV-1 encephalitis may cause long term memory
loss. HSV-1 replication is suppressed in Lysine-
rich/arginine - poor environments, and population
studies suggest that diets high in Lysine and low in ar-
ginine may be associated with lower rates of AD. There
are no prospective studies of the efficacy of lysine sup-
plementation to prevent or reduce the incidence of AD.
Supplementation with adequate doses of Lysine could
prevent the development of AD (Rubey RN, 2010).
Hair Loss
In addition to calcium, L- Lysine also helps your body
absorb iron and zinc. These minerals are important to
the health of your skin and hair. According to studies,
vegans with a Lysine-deficient diet may have poor hair
health and hair loss as a result of decreased zinc and
iron absorption. While Lysine alone has not been
shown to prevent hair loss, one study described
showed that women with iron deficiencies who sup-
plement with both iron and Lysine can reduce iron de-
ficiency-associated hair loss by 50 percent (Rushton
DH, 2002).
Shingles
Shingles (herpes zoster) is a painful, blistering skin rash
due to the varicella-zoster virus, the virus that causes
chickenpox. It usually strikes people with weak im-
Meenu Singh et al., Int. J. Res. Pharm. Sci., 2(4), 2011, 637-642
640 ©JK Welfare & Pharmascope Foundation | International Journal of Research in Pharmaceutical Sciences
mune systems and the elderly, causing painful and in-
flamed blisters. L-Lysine is listed as a purported treat-
ment of the condition, according to the University of
Michigan Health Systems.
Cancer
There are Lysine conjugates that show promise in the
treatment of cancer, by causing cancerous cells to de-
stroy themselves when the drug is combined with the
use of phototherapy, while leaving non-cancerous cells
unharmed (Science Daily, 2008 and Roomi MW et al.,
2006).
Cardiovascular diseases
Limited studies suggest that a high-Lysine diet or L-
Lysine supplements may have a moderating effect on
blood pressure and the incidence of stroke (Flodin
1997). It may be beneficial in helping ensure heart
health because of its ability to inhibit the build up of
junk on the walls of our arteries that can prevent blood
and the nutrients it carries from arriving at their desti-
nations on time (Mc Beath M, 1993).
Aging
L-Lysine is instrumental in the formation of collagen,
which supports the skin, muscles, and joints. We lose
collagen as we age, and the supplementation with L-
Lysine may help keep our skin looking young and
healthy. Collagen is, of course, also necessary for the
repair of all connective tissue (ligaments, cartilage,
joints, skin, bones, and teeth) and plays a key role in
the growth and repair of many tissues. Thus, healthy
collagen may help athletes recover more quickly from
intense workouts and protect some of the more fragile
tissues of the body (Flakoll P et al., 2004).
SAFETY PROFILE OF L-LYSINE
Although L-Lysine is an essential part of the diet, the
safety of concentrated Lysine supplements has not
been well studied. In animal studies, high dosages have
caused gallstones and elevated cholesterol levels
(Kritchevsky D. et al., 1984, Leszczynski D.E. and Kum-
merow F.A., 1982). Maximum safe dosages for young
children, pregnant or nursing women, or those with
severe liver or kidney disease have not been estab-
lished. Although rare, abdominal cramps and diarrhoea
have been seen with extremely high amounts (15 to 40
grams per day). Increased risk of gallstones and ele-
vated cholesterol have been reported (in animal stud-
ies only) where high amounts were used. Lysine sup-
plementation is not advised for children. No known
toxicity found with Lysine use. Most people need about
1 g of lysine per day. The requirement may be greater
for athletes and people recovering from major injuries,
especially burns. It appears to be most effective when
taken on an empty stomach with water. For increasing
the release of growth hormone, Lysine is recom-
mended before sleep or before exercise (Suminski RR
et al.., 1997). If taken in a 4:1 ratio with arginine, Lysine
may both prevent infection from the herpes virus as
well as prevent flare-ups in those who already have the
virus. Deficiency of Lysine has been linked to fa-
tigue/weakness, red eyes, dizziness, decreased atten-
tion span, anaemia, enzyme disorders, retarded growth
and immune disorders etc. Adverse Reactions Doses
greater than 10-15 g/day may cause gastrointestinal
discomfort with symptoms of nausea, vomiting and
diarrhoea. Clinical tests have found L-Lysine enhances
intestinal absorption and decreases renal excretion of
calcium. Lysine is contraindicated in people with the
rare genetic disorder hyperlysinaemia / hyperlysinuria.
High-dose lysine supplements should be used with cau-
tion in hypercalcaemic states, and by people with kid-
ney or liver disease. Safety is unknown for high-dose
supplements, however, dietary intake levels are safe.
FUTURE PROSPECTIVES
On the basis of studies it has been shown that the L-
Lysine has an inhibitory effect on the multiplication of
HSV in cell cultures. It appears to act as an antimetabo-
lite and competes with the viral growth promoting ac-
tion of arginine. It has been found that if L-Lysine is
taken more than 1000 mg three times per day for 6
months or more, it decreases the recurrence rate of
herpes simplex attacks and severity of the infection
and, promotes healing time of recurrent HSV infection.
Although some results are promising, none of the stud-
ies are large enough to give conclusive answers. At this
point, more evidence is needed to determine whether
Lysine is effective for preventing herpes simplex.
In vitro tests with human osteoblasts indicate that L-
Lysine has a positive effect on osteoblast proliferation,
activation and differentiation. Results suggest that L-
Lysine can both enhance intestinal Ca
++
absorption and
improve the renal conservation of the absorbed Ca
++
.
The combined effects may contribute to a positive Ca
++
balance, thus suggesting a potential usefulness of L-
Lysine supplements for both preventive and therapeu-
tic interventions in osteoporosis.
Due to lack of sufficient data it is difficult to predict the
use of L-Lysine in the treatment of anxiety and mood
disturbances hence further studies are required in this
field to understand the mechanism and to provide firm
evidence for its uses as an antianxiety agent.
Among the available options for the treatment of mi-
graine, lysine clonixinate (LC) and Lysine acetylsalicy-
late have proved effective in migraine. With the help of
further studies we could find out other formulations of
L-Lysine which would be considerably effective over
conventional method of treatments.
To access the effective uses of L-Lysine in the treat-
ment or prevention of Alzheimer's dementia, hair loss,
shingles, cancer, cardiovascular diseases and aging etc.,
a significant number of studies have to be performed
in order to determine the mechanism and optimum
dose of L-Lysine for these pathological conditions.
Meenu Singh et al., Int. J. Res. Pharm. Sci., 2(4), 2011, 637-642
©JK Welfare & Pharmascope Foundation | International Journal of Research in Pharmaceutical Sciences 641
CONCLUSION
About 60 years has been passed since the discovery of
L-Lysine, an essential amino acid which is capable of
preventing many pathological conditions. Since then,
several studies have been performed to understand
the mechanisms and to titre the optimum doses of L-
Lysine mainly in the treatment of herpes simplex virus
infection. A typical therapeutic dosage of L-Lysine, if
taken 1 g three times per day or more for 6 months, it
may be helpful for herpes infections. This can be taken
as a regular part of diet and will prevent herpes flare
ups or perhaps at the first sign of attack. Above men-
tioned studies provided the insight for the use of L-
Lysine in the treatment or prevention of osteoporosis,
migraine, Alzheimer's dementia, hair loss, shingles,
cancer, cardiovascular diseases and aging. L-Lysine
serves as a very good candidate for the future studies
and it may act as a main target for new drug therapy in
aforementioned diseases.
ACKNOWLEDGEMENT
Dr. DMR is highly thankful to UGC, New Delhi and CSIR.
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... The first polyamine to be discussed here is ε-poly-L-lysine, or ε-PL. Despite lysine's initial isolation from milk in 1889 [319], lysine in its polymeric form was not discovered until 1977, when Shima and Sakai [320] announced their discovery of what they called the "lysine polymer", isolated from the culture filtrate of a bacterial strain similar to Streptomyces albulus [320,321]. This alkaloid polymer structure is characterised by the L-chirality of the constituent amino acid and by the position of the peptide bond, connecting lysine's carboxylic acid group, and its ε-amine group ( Figure 15) [321,322]. ...
... Despite lysine's initial isolation from milk in 1889 [319], lysine in its polymeric form was not discovered until 1977, when Shima and Sakai [320] announced their discovery of what they called the "lysine polymer", isolated from the culture filtrate of a bacterial strain similar to Streptomyces albulus [320,321]. This alkaloid polymer structure is characterised by the L-chirality of the constituent amino acid and by the position of the peptide bond, connecting lysine's carboxylic acid group, and its ε-amine group ( Figure 15) [321,322]. However, despite their successful identification of this novel biopolymer, Shima and Sakai [320] could not determine the physiological function of ε-PL, though contemporary research has now suggested that ε-PL confers antimicrobial and acid-stress protection in ε-PL accumulating genera [323]. ...
... A continuous problem with improvements to the Streptomyces sp. growth model has been the historical lack of data on the genes expressing ε-PL synthases, a problem which (exacerbated by a lack of ε-PL accumulating organisms) prevented genetic transfer into more industrially suited micro-organisms [321]. However, Yamanaka et al. [347] finally identified the first ε-PL synthase, a non-ribosomal peptide synthase, which was followed up by the first heterologous expression in another Streptomyces species (Streptomyces lividans). ...
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Plastics have found widespread use in the fields of cosmetic, engineering, and medical sciences due to their wide-ranging mechanical and physical properties, as well as suitability in biomedical applications. However, in the light of the environmental cost of further upscaling current methods of synthesizing many plastics, work has recently focused on the manufacture of these polymers using biological methods (often bacterial fermentation), which brings with them the advantages of both low temperature synthesis and a reduced reliance on potentially toxic and non-eco-friendly compounds. This can be seen as a boon in the biomaterials industry, where there is a need for highly bespoke, biocompatible, processable polymers with unique biological properties, for the regeneration and replacement of a large number of tissue types, following disease. However, barriers still remain to the mass-production of some of these polymers, necessitating new research. This review attempts a critical analysis of the contemporary literature concerning the use of a number of bacteria-derived polymers in the context of biomedical applications, including the biosynthetic pathways and organisms involved, as well as the challenges surrounding their mass production. This review will also consider the unique properties of these bacteria-derived polymers, contributing to bioactivity, including antibacterial properties, oxygen permittivity, and properties pertaining to cell adhesion, proliferation, and differentiation. Finally, the review will select notable examples in literature to indicate future directions, should the aforementioned barriers be addressed, as well as improvements to current bacterial fermentation methods that could help to address these barriers.
... Because of its storage capacity and slower metabolism, L-lys is the most preserved one among the essential amino acids [8]. Taking L-lys daily can help prevent cold sores and genital herpes, as reported by the University of Maryland Medical Center [9]. L-lys is found to mediate the absorption of calcium and reduces the release of calcium in urine which help against osteoporosis-related diseases. ...
... L-lys is found to mediate the absorption of calcium and reduces the release of calcium in urine which help against osteoporosis-related diseases. Similarly, L-lys along with L-arginine enhance the activity of bone-forming cells and increase the production of collagen [9]. Rubey et. ...
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Typhoid fever is caused by a pathogenic, rod-shaped, flagellated, and Gram-negative bacterium known as Salmonella Typhi. It features a polysaccharide capsule that acts as a virulence factor and deceives the host immune system by protecting phagocytosis. Typhoid fever remains a major health concern in low and middle-income countries, with an estimated death rate of ~200,000 per annum. However, the situation is exacerbated by the emergence of the extensively drug-resistant (XDR) strain designated as H58 of S. Typhi. The emergence of the XDR strain is alarming, and it poses serious threats to public health due to the failure of the current therapeutic regimen. A relatively newer computational method called subtractive genomics analyses has been widely applied to discover novel and new drug targets against pathogens, particularly drug-resistant ones. The method involves the gradual reduction of the complete proteome of the pathogen, leading to few potential and novel drug targets. Thus, in the current study, a subtractive genomics approach was applied against the Salmonella XDR strain to identify potential drug targets. The current study predicted four prioritized proteins (i.e., Colanic acid biosynthesis acetyltransferase wcaB, Shikimate dehydrogenase aroE, multidrug efflux RND transporter permease subunit MdtC, and pantothenate synthetase panC) as potential drug targets. Though few of the prioritized proteins are treated in the literature as the established drug targets against other pathogenic bacteria , these drug targets are identified here for the first time against S. Typhi (i.e., S. Typhi XDR). The current study aimed at drawing attention to new drug targets against S. Typhi that remain largely unex-plored. One of the prioritized drug targets, i.e., Colanic acid biosynthesis acetyltransferase, was predicted as a unique, new drug target against S. Typhi XDR. Therefore, the Colanic acid was further explored using structure-based techniques. Additionally, ~1000 natural compounds were docked with Colanic acid biosynthesis acetyltransferase, resulting in the prediction of seven compounds as potential lead candidates against the S. Typhi XDR strain. The ADMET properties and binding energies via the docking program of these seven compounds characterized them as novel drug candidates. They may potentially be used for the development of future drugs in the treatment of Typhoid fever. Citation: Jalal, K.; Khan, K.; Hassam, M.; Abbas, M.N.; Uddin, R.; Khusro, A.; Sahibzada, M.U.K.; Gajdács, M.
... Because of its storage capacity and slower metabolism, L-lys is the most preserved one among the essential amino acids [8]. Taking L-lys daily can help prevent cold sores and genital herpes, as reported by the University of Maryland Medical Center [9]. L-lys is found to mediate the absorption of calcium and reduces the release of calcium in urine which help against osteoporosis-related diseases. ...
... L-lys is found to mediate the absorption of calcium and reduces the release of calcium in urine which help against osteoporosis-related diseases. Similarly, L-lys along with L-arginine enhance the activity of bone-forming cells and increase the production of collagen [9]. Rubey et. ...
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L-lysine (L-lys) had long been comprehended as an essential amino acid for humans. There were reports that the absence or inadequate availability of L-lys in the diet may lead to mental and physical impairments. The present study was designed to explore the effects of L-lys on body weight changes, cumulative food intake, anxiety-like behavior and pain perception in rats. 5-Hydroxytryptamine (5-HT, serotonin) metabolism, and tryptophan (Trp) levels in the midbrain (MB), hippocampus (HP), and prefrontal cortex (PFC) were also determined. Animals were treated with L-lys in doses of 0.5 g/kg and 1 g/kg for 20 days and behavioral studies were performed on day 1st and day 20th. After monitoring behaviors on day 20th, animals were killed to collect the serum and brain regions MB, HP and PFC. 5-HT metabolism and Trp levels were determined by HPLC-EC. The treatment produce no effect on food intakes but body weights were reduced. 20 days administration of L-lys produced an anxiolytic effect and increased exploratory activity on day 1st. Repeated administration of L-lys increased 5-HT levels in the PFC and HP. 5-Hydroxyindoleacetic acid (5-HIAA), the metabolite of 5-HT, decreased in the HP. Trp, the precourser of 5-HT, decreased in the PFC. Results suggested a decrease in 5-HT degredation in enhancing 5-HT levels. Results of in-silico analysis showed that lysine had a potential binding affinity for MAO (monoamine oxidase) A and B with an energy of (−4.8 kcal/mol and −5.3 kcal/mol) respectively. The molecular dynamic simulation study revealed the stability of L-lys after 10 ns for each protein. Conclusively, the present study showed that L-lys produced an anxiolytic effect and reduced body weight. These beneficial effects were associated with an increase in 5-HT levels in the PFC and HP. In-silico analysis suggested that 5-HT increase were due to the binding of L-lys with MAOs resulting in an inhibition of the degradation of monoamine.
... Additionally, lysine had the highest composition of the amino acid, which may be an important attribute of the fruit peel. This is because Lysine is an important unit for all protein synthesis (Singh et al., 2011). It plays a crucial role in absorption of calcium, muscle protein synthesis, muscle injury recovery and production of functional proteins such as hormones, enzymes and antibodies (Singh et al., 2011). ...
... This is because Lysine is an important unit for all protein synthesis (Singh et al., 2011). It plays a crucial role in absorption of calcium, muscle protein synthesis, muscle injury recovery and production of functional proteins such as hormones, enzymes and antibodies (Singh et al., 2011). ...
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The peel of pomegranate fruit contains antioxidant phytochemicals that may potentiate health benefits but remain under-explored. We evaluated the antioxidant, nutritional and phytochemical profiles of the peel of the “Wonderful” variety pomegranate and its influence on oxidative metabolic alterations in hepatic tissue. The peel contained appreciable amounts of some beneficial trace minerals and both essential and non-essential amino acids. Mostly Omega 3 and 6 fatty acids were found. The peel extracts exhibited in vitro radical scavenging and Fe³⁺ reducing antioxidant activities and dose-dependently prevented oxidative stress-induced lipid peroxidation increase and GSH depletion in both Chang liver cells (IC50 = 18.0 ± 1.46 and 11.2 ± 0.99 µg/mL, respectively) and isolated rat liver (IC50 = 96.7 ± 3.34 and 19.4 ± 3.36 µg/mL, respectively). The antioxidant effects were comparable to that of ascorbic and correlated with their phenolic profile. HPLC analysis further identified antioxidant phenolic acids (gallic acid, syringic acid ferulic acid p-coumaric acid or trans-4-hydroxycinnamic acid, etc.). The peel did not cause notable cytotoxicity in liver and kidney cells, which suggest minimal safety concerns. Metabolomics analysis revealed alterations in fatty acid, amino acids, and nucleic acid metabolisms following the induction of oxidative stress. These alterations were improved in the acetone extract-treated tissues, with concomitant activation of vitamin and selonocompound metabolisms. Data suggest that the fruit peel of “Wonderful” pomegranate may be an underutilized source of functional nutrients and antioxidants phenolic acids for optimum body function and mitigation hepatic oxidative damage and metabolic alterations as well as associated diseases. Practical applications Although underutilized, documented evidence have shown that the wastes, like peels from fruits contain more phytochemicals than the edible pulp, making them potential sources of bioactive principles. In this study we exposed the nutritional, phytochemical and oxidative stress-related medicinal benefits of the peel of “Wonderful” pomegranate variety. The peel could ameliorate oxidative hepatic metabolic alterations. The peel of this fruit could be a source of beneficial micro and macro nutrients, as well as bioactive phenolics to improve oxidative health and mitigate oxidative hepatic damage and associated disease states. Medicinally utilizing the fruit’s peel could reduce underutilized fruit wastes, increase the value of the fruit and benefit the bioeconomy.
... L-Lysine is an integrant building block for all proteins in the human body. Its plays an important role in calcium absorption, building muscle protein, recovering from sports injuries or surgery, and the body's production of enzymes, antibodies, and hormones (Singh et al. 2011). ...
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The aim of this research was the comparative study of the content of the amino acids in the herb and tubers of Stachys sieboldii. The study of the amino acid composition of the raw materials was carried out using high-performance liquid chromatography (HPLC). The results obtained have shown that the aerial parts of plants investigated have higher amino acid content than the underground organs. Free and bound L-aspartic acid, L-proline, and L-phenylalanine were present in the analyzed samples in the greatest amount. Moreover, L-cysteine was found only in Stachys sieboldii tubers in amounts (8.11 mg/g). This research established that Stachys sieboldii herb and tubers have the most suitable amino acids composition and are prospective for further pharmacological studies.
... Menurut Bahadoran et al. (2016), kandungan asam amino L-Arginin pada protein nabati berperan dalam mengatur tekanan darah dan berpotensi menurunkan resiko penyakit jantung koroner. Manfaat yang sama dalam pencegahan penyakit kardiovaskular juga terjadi karena adanya potensi dari asam amino L-lysin selain berpotensi dalam pencegahan demensia alzhemier (Singh et al., 2011). ...
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Chapter
In many of the Asian countries, fish roe products are considered important condiments and are consumed not only as a source of dense nutrients but also as a sign of strong cultural customs from the time immemorial. Fish roes are consumed and enjoyed in fresh or processed forms (e.g., salted, fermented, canned, or smoked). The main principles of fish roe processing are the reduction of moisture content and the use of curing agents and spices to enhance shelf life, nutritional value and sensory attributes. Fish roe is rich in protein, contains all essential and nonessential amino acids and has tremendous bioactivities such as anticancer, antiinflammatory, antihypertensive, and immunomodulatory activities. The lipid fraction of fish roe contains a substantial amount of the health-beneficial long-chain ω-3 polyunsaturated fatty acids, for example, eicosapentaenoic acid (EPA, C20:5n3) and docosahexaenoic acid (DHA, C22:6n3). These essential fatty acids are effective in preventing atherosclerosis, maintaining favorable blood lipid profile, aiding in brain maturity, exerting antiinflammatory activity, and relieving rheumatoid arthritis. Also, there are some health-beneficial fatty acids such as linoleic acid, linolenic acid, arachidonic acid, palmitoleic acid, and oleic acid available in fish roe. Additionally, fish roe contains a substantial amount of essential trace elements, that is, K, S, P, Na, Mg, and Zn, which contribute to crucial biological functions and health benefits. However, fish roe and roe products are associated with several biological, chemical, and physical hazards if they are not handled and processed properly, which makes them unsafe for consumption. Therefore guidelines and processing recommendations have been streamlined to ensure that the roe and roe products are safe for public health.
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Knowledge about viral characteristics, mechanisms of entry into the host cell and multiplication/dissemination can help in the control and treatment of viral pathologies. Several nutritional factors linked to the host, may favor the viral multiplication, and their control, may lead to new prophylactic alternatives and/or antiviral therapies. The objective of this review is to discuss the relationship between the amino acid L‐lysine and the control of viral infections, aiming at a possible therapeutic property. This research used databases such as PubMed, Web of Science, Scielo, Medline and Google Scholar, as well as searching for references cited by journals. The time frame covered the period between 1964 and January 2022. The observed studies have shown that the usual antiviral therapies are not able to interfere with the viruses in their latent state, however, they can interfere with the adhesion and fusion of viral particles or the production of proteins, which play an important role in viral epidemiology and control, particularly in the initial moment and in the reactivation. Lysine is an amino acid that can interfere mainly in the formation of capsid proteins and DNA by a competitive antagonism with amino acid arginine, which is an essential amino acid for some viruses , and also by promoting the increase of arginase, increasing the catabolism of arginine. Although there is evidence of the importance of L‐lysine in viral control, more studies are needed, with a view to new antiviral therapies.
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There is a growing body of evidence that implicates the herpes simplex type 1 virus (HSV-1) in the development of Alzheimer's dementia (AD). HSV-1 has been found to be present in the cerebrum of the great majority of older adults, and in many of the same areas of the brain that are affected by AD. When active, the virus may contribute to the formation of the neuro-fibrillary tangles and amyloid plaques characteristic of AD. Like AD, HSV-1 encephalitis may cause long term memory loss. HSV-1 replication is suppressed in lysine-rich/arginine - poor environments, and population studies suggest that diets high in lysine and low in arginine may be associated with lower rates of AD. There are no prospective studies of the efficacy of lysine supplementation to prevent or reduce the incidence of AD. Supplementation with adequate doses of lysine could prevent the development of AD.
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L-lysine has an inhibitory effect on the multiplication of herpes simplex virus in cell cultures. We have evaluated the prophylactic effect of L-lysine monohydrochloride 1000 mg daily on recurrent herpes simplex labialis in 65 patients in a double-blind, placebo-controlled, crossover study. After 12 weeks of lysine treatment the patients shifted to placebo treatment for a similar period. On the whole, lysine prophylaxis had no effect on the recurrence rate of herpes simplex. However, significantly more patients were recurrence-free during lysine than during placebo treatment (p = 0.05), suggesting that certain patients may benefit from prophylactic lysine administration. In the herpes lesions described, lysine had no effect on the rate of healing or on the appearance of the lesions at their worst.
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Calcium deficiency contributes to age-related bone loss; consequently, any preventive approach to osteoporosis should include dietary Ca adjustment or supplementation. The ideal Ca supplement would yield the greatest bioavailability. Studies in animals have shown that dietary supplements with certain amino acids, particularly L-lysine, can increase Ca absorption. Therefore, we examined the potential effect of this essential amino acid on Ca metabolism in humans. In one study, the acute effects of an oral Ca load (3 g as CaCl2) administered with or without 400 mg of L-lysine were compared in 15 healthy and 15 osteoporotic women. In all cases, the oral Ca load determined a progressive increase in serum total Ca and Ca2+ and a concomitant decrease in neophrogenous cAMP. As expected, a progressive increase in urinary Ca excretion was also observed, except in the L-lysine-treated healthy subjects, who exhibited a blunted calciuric response to the Ca load. In a second study, the effects of a short-term dietary supplementation with either L-lysine, L-valine, or L-tryptophan (800 mg/day) on 47Ca fraction absorption were compared in 45 osteoporotic patients. L-Lysine but not L-valine or L-tryptophan significantly increased the intestinal absorption of the mineral. Our results suggest that L-lysine can both enhance intestinal Ca absorption and improve the renal conservation of the absorbed Ca. The combined effects may contribute to a positive Ca balance, thus suggesting a potential usefulness of L-lysine supplements for both preventive and therapeutic interventions in osteoporosis.
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A double-blind, placebo-controlled, multicenter trial of oral L-lysine monohydrochloride for the prevention and treatment of recurrent herpes simplex (HSV) infection was conducted. The treatment group was given L-Lysine monohydrochloride tablets (1,000 mg L-lysine per dose) 3 times a day for 6 months. A total of 27 (6 male and 21 female) subjects on L-lysine and 25 (6 male and 19 female) subjects on placebo completed the trial. The L-lysine treatment group had an average of 2.4 (p less than 0.05) less HSV infections, symptoms were significantly (p less than 0.05) diminished in severity and healing time was significantly reduced (p less than 0.05). L-Lysine appears to be an effective agent for reduction of occurrence, severity and healing time for recurrent HSV infection.
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In the studies conducted, arginine deficiency suppressed herpes simplex virus replication in tissue culture. Lysine, an analog of arginine, as an antimetabolite, antagonized the viral growth-promoting action of arginine. The in vitro data may be the basis for the observation that patients prone to herpetic lesions and other related viral infections, particularly during periods of stress, should abstain from arginine excess and may also require supplemental lysine in their diet.
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In a prospective, randomized, double-blind, placebo-controlled, cross-over study of forty-one patients we found that oral ingestion of 1,248 mg a day of L-Lysine monohydrochloride shows evidence of decreasing the recurrence rate of herpes simplex attacks in nonimmunocompromised hosts. A dose of 624 mg a day was not effective. L-Lysine may also be capable of decreasing the severity of symptoms associated with recurrences. Neither dosage showed any evidence of shortening the healing time compared to placebo.
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Lysine and arginine supplements were fed to 5-day-old chicks to test whether they would develop hypercholesterolemia in response to excess lysine in a fashion similar to mammals. Chicks developed hypercholesterolemia with a 4-5% lysine but not with arginine supplementation. These results indicate the lysine induced hypercholesterolemia is not due to anaplerotic interactions of arginine and lysine with the urea cycle.