Existence of Lathyrus Beyond Lathyrism

Abstract

Lathyrus ( Lathyrus sativus ) pulse is better known as the causative agent of a crippling neurological disorder called Lathyrism. Patients suffer from gradual progressive increasing spasticity and bony changes, which ultimately result in crippling stages throughout life. The present literature aimed to discover the L. sativus existence beyond Lathyrism. We searched the electronic databases of PubMed and Google Scholar using the keywords. We have taken reference to previously published literature on the Lathyrus and Lathyrism. In the current literature, we have found that Lathyrus is nutritionally rich and tolerant to different kinds of environmental stress, and it could be included in human meals or used to feed animals. In India, Lathyrus is banned due to its proposed neurotoxicity. However, the literature suggests that alone, Lathyrus cannot cause Lathyrism. Other factors like environmental factors such as availability of water in paddy fields, associated genetic disorders, and metal content of soil decide the amount of beta-N-oxalyl-amino-L-alanine and Oxalyl-diamino-propionic acid (ODAP) in Lathyrus seeds and its effects. There are new technologies and physical methods that can minimize the toxic nature of Lathyrus . A low ODAP containing Lathyrus is an economic cereal for poor people and grazing animals.

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208 © 2023 Journal of Preventive, Diagnostic and Treatment Strategies in Medicine | Published by Wolters Kluwer - Medknow
Existence of
Lathyrus
Beyond Lathyrism
Vineeta Singh, Yeshashwini Mishra1, Vijaya Nath Mishra
Abstract
Lathyrus (Lathyrus sativus) pulse is better known as the causative agent of a crippling neurological
disorder called Lathyrism. Patients suffer from gradual progressive increasing spasticity and bony
changes, which ultimately result in crippling stages throughout life. The present literature aimed to
discover the L. sativus existence beyond Lathyrism. We searched the electronic databases of PubMed
and Google Scholar using the keywords. We have taken reference to previously published literature
on the Lathyrus and Lathyrism. In the current literature, we have found that Lathyrus is nutritionally
rich and tolerant to different kinds of environmental stress, and it could be included in human meals
or used to feed animals. In India, Lathyrus is banned due to its proposed neurotoxicity. However,
the literature suggests that alone, Lathyrus cannot cause Lathyrism. Other factors like environmental
factors such as availability of water in paddy elds, associated genetic disorders, and metal content
of soil decide the amount of beta‑N‑oxalyl‑amino‑L‑alanine and Oxalyl‑diamino‑propionic acid
(ODAP) in Lathyrus seeds and its effects. There are new technologies and physical methods that
can minimize the toxic nature of Lathyrus. A low ODAP containing Lathyrus is an economic cereal
for poor people and grazing animals.
Keywords:
Lathyrus ban, Lathyrus sativus, ODAP, ODAP toxicity
Introduction
Lathyrus sativus (L. sativus), also known as
grass pea, is a legume used for thousands
of years as a food source. However, it is
associated with a neurological disorder
known as Lathyrism, characterized by
progressive spasticity and bony changes that
ultimately lead to a lifetime disability.[1] This
disorder is caused by ingesting legumes from
the genus Lathyrus, particularly L. sativus.
In 1961, Dr. Gopalan reported 27 cases
of spastic paraparesis with a history of
L. sativus ingestion. Following this report,
the Government of India banned L. sativus
pulse due to its association with corticospinal
tract degeneration, lower limb spasticity, and
bony degenerative disorders.[2]
However, newer research suggests that
L. sativus alone cannot be blamed for
Lathyrism. Environmental factors such as
the availability of water in paddy elds,
genetic disorders, and the metal content
of soil also determine the amount of
beta‑N‑oxalylamino‑L‑alanine (BOAA)
and Oxalyl‑diamino‑propionic acid (ODAP)
in L. sativus and its effects on individuals
who consume it. BOAA and ODAP are the
two central neurotoxins responsible for
Lathyrism.[2] L. sativus has a rich history, and
its existence in ancient tombs of Egyptian
Pharaohs is mentioned in ancient Hindu
writings around 400 BC. During the Spanish
War of Independence, it served as a famine
food, leading to a rise in Lathyrism cases. In
World War II, feeding Jewish detainees solely
with grass peas, also known as L. sativus, in a
concentration camp in Transnistria resulted
in Lathyrism.[3] The perception of L. sativus
in the Indian population has been discussed
for many years. After six decades, the ban on
L. sativus pulse has been lifted from all Indian
states except Uttar Pradesh, the country’s
most populous state.
In addition to L. sativus, Lathyrus cicera is
another legume species generally grown as
Address for
correspondence:
Dr. Vijaya Nath Mishra,
Department of Neurology,
IMS, BHU, Varanasi,
Uttar Pradesh, India.
E-mail: vnmishra_2000@
yahoo.com
Submitted: 12-Aug-2023
Revised: 18-Oct-2023
Accepted: 28-Nov-2023
Published: 22-Dec-2023
Department of Neurology,
IMS, BHU, 1Department
of Psychology, Faculty of
Social Sciences, BHU,
Varanasi, Uttar Pradesh,
India
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DOI:
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How to cite this article: Singh V, Mishra Y, Mishra VN.
Existence of Lathyrus beyond lathyrism. J Prev Diagn
Treat Strat Med 2023;2:208-17.
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Journal of Preventive, Diagnostic and Treatment Strategies in Medicine - Volume 2, Issue 4, October-December 2023 209
a winter crop. Vicia articulata, a traditional crop legume
found in Santorini (Thera), Greece, is also related to
L. sativus and is near extinction. It is valuable for its future
need in archaeobotany/palaeoethnobotany.[4]
Lathyrism is a neurological disorder caused by the
excessive consumption of L. sativus, also known as
grass pea (legume), grown and consumed as a cheap
source of protein and calories, particularly in developing
countries.[5] L. sativus is a drought‑tolerant crop that
cultivates in different soil types, including sandy and
clay. It is also tolerant to pests and diseases, which makes
it a relatively low‑maintenance crop. The crop is typically
sown during the dry season and harvested in the rainy
season. In some regions, it is intercropped with other crops,
such as cereals or vegetables, which can help to increase
soil fertility and provide additional income for farmers. In
recent years, there has been renewed interest in L. sativus
as a potential crop for food security and nutrition in
developing countries. The crop is a good source of protein,
ber, and other vital nutrients and can be essential to a
healthy and balanced diet. However, it is vital to ensure
that the crop is prepared correctly and consumed in
moderation for the avoiding any potential health risks.[6]
Materials and Methods
While carrying out this review, Internet‑based
scientic literature scrutiny was performed by different
bibliographic databases namely Google Scholar, Wiley,
PubMed, TOXNET, and Science Direct using keywords
as L. sativus/toxicity and its benefits. Selection and
inclusion criteria were based on articles published in the
English language only.
Ethics statement
This study did not have any involvement or interaction
with human or animal subjects.
Inclusion criteria
The scientic research articles found on Internet were
screened based on its relevance.
Exclusion criteria
Articles with Lathyrus subtypes were kept out of the
scope of collation and discourse.
Discussion
Lathyrism onset throughout the world
(epidemiology)
Lathyrism is a chronic toxic nutritional, neurological
disease caused by long‑term or subacute ingestion of
our from the drought-resistant chickling pea (L. sativus).
Lathyrism exists in three forms depending on its pathology:
neurolathyrism, osteolathyrism, and angiolathyrism,
which differ in their symptoms and the body tissues
affected. Neurolathyrism is the most common and
characterized by spastic paraparesis affecting the lower
limbs, which can progress to complete paralysis.[7]
Lathyrism has been reported in various parts of the world,
particularly in regions where L. sativus is a staple food.
Historically, outbreaks of Lathyrism have been reported
in various regions, including parts of Europe, Asia, and
Africa. One of the most well‑known outbreaks occurred
in Ethiopia in the 1970s, where thousands of people
were affected by the disorder due to a severe famine
that led to the widespread consumption of L. sativus.
In recent years, there have been reports of Lathyrism in
various parts of the world, including India, Bangladesh,
and Nepal. The symptoms of Lathyrism usually appear
after a prolonged period of consumption of L. sativus
seeds, which can range from several months to several
years. The disorder primarily affects the central nervous
system, and the symptoms include spastic paraplegia or
tetraplegia, muscle weakness, gait disturbances, loss of
sensation, and bladder and bowel dysfunction.[8]
Lathyrus sativus cultivation in the world
It is primarily cultivated in developing countries,
particularly South Asia, North Africa, and the Middle
East. India is the world’s largest producer of L. sativus,
followed by Ethiopia, Bangladesh, and China. Other major
producers of L. sativus include Pakistan, Nepal, Morocco,
and Iran. L. sativus is a drought‑tolerant crop that can be
cultivated in different soil types, including sandy and clay
soils. It is also tolerant to pests and diseases, making it
a relatively low‑maintenance crop. The crop is typically
sown during the dry season and harvested in the rainy
season. In recent years, there has been renewed interest
in L. sativus as a potential crop for food security and
nutrition in developing countries. The crop is a good
source of key nutrients such as protein, ber, and other
crucial nutrients and might be an important part of a
healthy and balanced diet. However, to ensure that the
crop is prepared correctly and consumed in moderation.
It is essential to avoid the potential health risks associated
with excessive consumption of certain antinutritional
factors.[9] Other major producers of L. sativus include
Pakistan, Nepal, Morocco, and Iran.[10‑13]
Etiological agent for lathyrism
Lathyrism is a neurological disorder caused by ingesting
a neurotoxin called BOAA found in certain species of
grass peas (L. sativus) and other related legumes. The
consumption of large amounts of these legumes over an
extended period can lead to the accumulation of BOAA
in the body, which can cause damage to the nervous
system and result in symptoms such as weakness and
paralysis in the lower limbs, spasticity, and impaired
gait. Therefore, the etiological agent for Lathyrism is
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210 Journal of Preventive, Diagnostic and Treatment Strategies in Medicine - Volume 2, Issue 4, October-December 2023
the neurotoxin BOAA present in certain legumes, such
as grass peas [Figure 1]. On the isolation of BOAA from
L. sativus seeds, the neurotoxic property of the agent was
studied on various experimental animals.[14]
Chemistry
L. sativus sp. neurotoxin has amino acid properties
identied 33 years earlier. Three nomenclatures are used
to describe the P‑isomer of the acutely neurotoxic amino
acid: (a) BOAA, (b) ODAP, and (c) L‑3‑oxalyl amino‑2
amino‑propionic acid having the following structure:
HOOC‑CH (NH2]‑CH2‑NH CO COOH.[15]
Mechanism
Lathyrism involves the accumulation of BOAA in
the body, which leads to the activation of specific
mechanisms that ultimately cause damage to the nervous
system. BOAA is an excitotoxic amino acid, which means
that it overstimulates nerve cells and leads to their death.
BOAA works by inhibiting the activity of an enzyme
called aspartate aminotransferase (AAT), essential for
metabolizing the excitatory neurotransmitter glutamate.
Glutamate is a key neurotransmitter involved in the
transmission of signaling among the nerve cells of the
brain and spinal cord. When BOAA inhibits AAT, it
increases the levels of glutamate in the body, which can
overexcite nerve cells and lead to their death. The specic
areas of the nervous system affected by Lathyrism vary
depending on the individual but typically include the
spinal cord and the lower extremities. The symptoms
of Lathyrism include weakness and paralysis in the
lower limbs, spasticity, and impaired gait. In severe
cases, Lathyrism can lead to permanent disability or
death. ODAP deciphers its action using excitotoxicity
and oxidative stress. Excitotoxicity terms define
neuronal injury induced by excessive stimulation of
glutamate receptors by Mechanism, which includes the
disturbance of intracellular calcium (Ca2+) homeostasis
and excessive free radicals’ production.[16] Here, we listed
the Mechanism through which it causes Lathyrism.
ODAP and excitotoxicity
ODAP is an unusual compound. Therein, it is one of the
foremost anionic amino acids known and is an honest
metal chelator, and a few of its features, especially
in vitro systems, could also be associated with this
property. Several in vitro cell culture studies have
established that beta‑N‑oxalyl‑L‑alpha‑beta diamino
propionic acid (L‑ODAP) is α‑amino‑3‑hydroxy‑5‑
methyl‑4‑isoxazole propionic acid (AMPA) receptor
agonist (glutamate receptor agonist), and this has been
investigated extensively. This excitotoxic theory has
been extensively believed to be accountable for all the
neurotoxic properties of ODAP and has been publicized
to some extent. ODAP (beta‑N‑oxalyl‑L‑alpha‑beta
diamino propionic acid) is the neurotoxin responsible for
developing Lathyrism. ODAP is a nonprotein amino acid
that is present in high concentrations in certain legumes,
particularly in the seeds of grass peas (L. sativus). ODAP
acts as an excitotoxin, which causes overstimulation
Figure 1: Overview of lathyrism onset. BOAA: Beta‑N‑oxalylamino‑L‑alanine, ODAP: Oxalyldiaminopropionic acid, L‑ODAP: β‑N‑Oxalyl‑L‑α,β‑diaminopropionic acid
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Singh, et al.: Lathyrus without lathyrism
Journal of Preventive, Diagnostic and Treatment Strategies in Medicine - Volume 2, Issue 4, October-December 2023 211
and death of nerve cells in the body. Excitotoxicity
occurs when there is an excess of glutamate, an essential
excitatory neurotransmitter in the brain, which leads to
the overactivation of receptors and subsequent damage
to neurons. ODAP leads to excitotoxicity by inhibiting the
activity of an enzyme called AAT, which is responsible
for the breakdown of glutamate. When AAT is inhibited,
there is a buildup of glutamate in the body, which leads
to the overstimulation of nerve cells and, ultimately,
their death. The effects of ODAP and excitotoxicity
are particularly pronounced in motor neurons, which
control the movement of the body. In Lathyrism, the
overstimulation of motor neurons in the spinal cord leads
to their death, resulting in the characteristic symptoms
of the disorder, including weakness and paralysis in the
lower limbs, spasticity, and impaired gait.[17]
Oxidative stress in neurolathyrism
Some studies suggest a radical oxygen species (ROS)
generation as a mechanism of ODAP toxicity in
rats following its focal hippocampal application.
Neurolathyrism is a neurological disorder caused by
the consumption of grass peas. While the primary
Mechanism of neurolathyrism is excitotoxicity, there
is also evidence to suggest that oxidative stress plays
a crucial role in the onset of the disorder. The state of
imbalance between the formation of reactive oxygen
species (ROS) and the body’s antioxidant defense system
is known as oxidative stress. ROS are unstable molecules
that can damage cells and tissues, and excessive ROS
production can lead to oxidative stress and cell death.
The brain is specically vulnerable to oxidative stress due
to its high metabolic activity and relatively low levels of
antioxidant enzymes. Research has shown that BOAA
can induce oxidative stress in the brain by increasing
the production of ROS and reducing the activity of
antioxidant enzymes. BOAA‑induced oxidative stress
can lead to lipid peroxidation, protein oxidation, and
DNA damage, which can ultimately lead to cell death.
The role of oxidative stress in neurolathyrism is not
fully understood, but it is thought to contribute to the
development of the disorder by degeneration of nerve
cells within the brain and spinal cord. Oxidative stress
may also interact with the excitotoxicity mechanism to
exacerbate the damage caused by BOAA.[18]
Inhibition of tyrosine aminotransferase by L‑ODAP
Most mechanisms suggested for ODAP toxicity come
short of explaining the species differences in susceptibility
to ODAP. In this context, the reported inhibition of
tyrosine aminotransferase (TAT) by ODAP in both in vivo
and in vitro proposes a fascinating alternate mechanism
of neurotoxicity. TAT is an enzyme responsible for
converting the amino acid tyrosine into a precursor
of the dopamine neurotransmitter. Dopamine is an
important neurotransmitter in the brain that is involved
in the regulation of movement, mood, and motivation.
L‑ODAP, the neurotoxin present in grass peas (L. sativus)
that causes Lathyrism, has been found to inhibit the
activity of TAT. This inhibition of TAT by L‑ODAP leads
to decreased dopamine production, which can result in a
range of neurological symptoms. The inhibition of TAT
by L‑ODAP can reduce dopamine concentration within
the brain, which can contribute to the motor symptoms
seen in Lathyrism, such as muscle weakness, spasticity,
and impaired gait. Dopamine deciency in the brain
is also associated with other neurological disorders,
such as Parkinson’s, characterized by movement and
tremors. The inhibition of TAT by L‑ODAP may also
have implications for regulating mood and motivation,
as dopamine is associated with the brain’s pleasure and
reward pathways. Low brain dopamine is associated
with depression and other mood disorders.[19]
Metabolism of ODAP in humans and animals
The very low incidence of neurolathyrism in cohorts
subsisting on Khesari dal has not been explained.
Even within a family not, most are vulnerable to
neurolathyrism. The fate of orally ingested ODAP from
L. sativus had not been examined intimately.[20]
Lathyrism (pathophysiology)
The pathophysiology of Lathyrism involves the
neurotoxic effects of two nonprotein amino acids, BOAA
and ODAP, which are found in high concentrations in
L. sativus seeds. BOAA and ODAP are potent excitotoxins
that cause damage to the corticospinal tract and other
motor pathways in the spinal cord and brain. This
damage results in a range of neurological symptoms,
including lower limb spasticity, hyperreexia, muscle
weakness, and muscle wasting. The neurotoxic effects of
BOAA and ODAP are due to their structural similarity
to the neurotransmitter glutamate, a crucial excitatory
neurotransmitter in the central nervous system. In
addition to the neurotoxic effects of BOAA and ODAP,
other factors such as environmental conditions, genetics,
and nutrition can also inuence the development and
severity of Lathyrism. For example, individuals who
are malnourished or have a deciency of Vitamin B6
may be more susceptible to the toxic effects of BOAA
and ODAP.[20]
Lathyrism in humans
The onset of human Lathyrism is gradual and insidious,
with symptoms typically appearing after several months
or years of consuming L. sativus seeds as a staple food
source. In humans, individuals of both sexes and each
age group are often affected, but the disease is most
prominent among young male adults. The symptoms of
the disease, as reported, usually begin suddenly a few
weeks or months after consumption of seeds of L. sativus.
There could be very frequent urination (30–40 times
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212 Journal of Preventive, Diagnostic and Treatment Strategies in Medicine - Volume 2, Issue 4, October-December 2023
during the night), prodromal sensory symptoms of pain,
prickling numbness, and cramps, but commonly the
patient suddenly feels weakness and heaviness in the
legs and loins, with tremulous muscles while bearing
weight. There is leg dragging, increased reexes, and
impaired ability to steer. In mild cases, only ankle and
knee movements are restricted by spasms, causing the
victim to steer rigidly on the balls of his feet, tilting the
pelvis. The earliest symptoms of human Lathyrism
include weakness and numbness in the legs, followed
by increased spasticity and muscle rigidity. As the
disease progresses, individuals with human Lathyrism
may experience muscle wasting and loss of mobility,
ultimately leading to a lifetime of disability. The severity
of Human Lathyrism can vary depending on several
factors, including the amount and duration of L. sativus
consumption, environmental conditions, genetics, and
nutrition. Individuals who are malnourished or have a
deciency of Vitamin B6 may be more susceptible to the
toxic effects of BOAA and ODAP.
There is no cure for Human Lathyrism, and treatment
typically involves supportive care, physical therapy, and
management of symptoms. Prevention of the disease
involves limiting the consumption of L. sativus seeds as
a staple food source and promoting the cultivation and
consumption of alternative food sources.[21]
Lathyrism in animals
Lathyrism is not limited to humans, and it can also affect
animals that consume L. sativus seeds. The disease has
been reported in several animal species, including horses,
cows, pigs, sheep, and chickens. In animals, Lathyrism
is characterized by a range of symptoms, including
muscle weakness, paralysis, and incoordination. The
severity of the disease can depend on the amount and
duration of L. sativus consumption, the age and health
of the animal, and other factors. In horses, Lathyrism
is known as “pea‑sickness” and has been reported in
several countries, including India, Spain, and Australia.
Horses with Lathyrism exhibit symptoms of ataxia,
muscle weakness, and paralysis, which can ultimately
lead to death. In cows, Lathyrism is known as “cholera”
or “kakke” and has been reported in India and other
countries. Cows with Lathyrism exhibit symptoms of
muscle weakness, hindquarter paralysis, and other
neurological problems. Prevention of Lathyrism in
animals involves limiting the consumption of L. sativus
seeds and promoting the cultivation and consumption
of alternative food sources. In some cases, treatment
may involve supportive care and management of
symptoms.[21]
Causes of alteration in ODAP content
Of all the grain legumes, L. sativus was best modied
to the poor soils of their environment. The suboptimal
concentration of minerals in the eld or experimental
culture solution can substantially affect plant
development and eventually inuence the yields and
ODAP levels in seeds or other tissues.[21]
Presence of certain micronutrients alters the
ODAP content
Micronutrients alter the ODAP level and it was found
that there are decreased levels of ODAP in response
to cobalt (Co) or molybdenum (Mo) when sprayed
with 0.5 ppm Co (nitrate) or 20 ppm Mo (ammonium
molybdate) salts at the utmost owering stage. In grass
pea seedlings, they also evidenced the effect of Mo on
ODAP amount in shoots and root, throughout which
Mo deciency (Mo) resulted in a noticeable increase in
ODAP levels in shoots at both 7–15 days, but within the
root only at 7 days after treatments. It was found that the
presence of zinc also alters the ODAP content. Further, a
broader investigation, growing Lathyrus species at up to
31 sites throughout southwestern Australia, conrmed
the increasing effect of phosphate fertilizer on toxins
within the seeds.[21]
Presence of certain macronutrients alters the
ODAP content
In addition to the consequences of micronutrients, the
amount of ODAP was also affected by macronutrients.
The decrease of the macronutrients such as nitrogen,
phosphorus, magnesium, or potassium in the Hoagland
solution caused a sharp increase in ODAP amount within
the ripe seed.[22‑25]
Presence of osmotic stresses
Due to drought
L. sativus is documented as a drought‑tolerant legume
crop; its several physiological processes will be severely
affected, resulting in a reduction of yield, even to early
senescence, when exposed to chronic periods of drought.
Because Lathyrism frequently occurs during drought
periods, the change in the content of ODAP in seeds
of grass peas under drought conditions has been of
particular concern.[26]
Due to high salinity
In saline habitats, the presence of high salt concentrations
makes it harder for plant roots to require water from
the environment, thereby causing water stress and
accumulating ions to toxic levels within the cytosol. It
was earlier found that the soil salinity within the farmers’
eld causes decreased seed ODAP content.[27]
Due to the effect of osmotic stress
Polyethylene glycol (PEG)‑6000 is often used to mimic
drought conditions; it simulates soil water stress by
creating negative water potential in the plants. Previous
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Journal of Preventive, Diagnostic and Treatment Strategies in Medicine - Volume 2, Issue 4, October-December 2023 213
literatures showed that the duration of PEG treatment
leads to raised ODAP content in the leaves of 15‑day‑old
seedlings. The change in contents of ODAP of cotyledons
showed a similar trend, but the utmost value occurred
at 2 days for both treatments and controls.[28]
Due to the presence of heavy metals
In hydroponic culture, adding cadmium (Cd) or
aluminum (Al) within the solution signicantly increased
the ODAP content of shoots or seeds. In hydroponic
culture, the addition of Cd or Al in the solution
signicantly increased the ODAP content of shoots or
seeds.[29]
Due to the presence of anti‑nutritional factor
Antinutritional and toxic factors in grass peas:
Anti-nutrients are well-dened as substances which,
by themselves or via their metabolic products arising in
living systems, hinder food application and affect animal
health and making.[30] L. sativus, also known as grass
pea or chickling pea, is often considered a pulse crop of
poor economic countries, particularly in parts of Asia
and Africa. Pulse crops harvested for the dry seed rich
in protein and other nutrients. L. sativus is an essential
crop in many areas because it is hardy, drought‑resistant,
and can grow in poor soil conditions. Drought resistance
makes L. sativus a good choice for farmers in regions
where other crops may not thrive. The seeds of L. sativus
are also relatively inexpensive, which means they can
provide a low‑cost source of protein for people in these
regions. It is essential to consume L. sativus in moderation
and to prepare it in a specic way to reduce the risk of
Lathyrism. Despite this potential risk, L. sativus remains
an essential crop for many farmers in poor economic
countries, as it provides a reliable source of protein
and can help to improve food security in low economic
countries.[30]
Exists as the pulse of the poor
L. sativus, also known as grass pea or chickling pea, is
often considered a pulse crop of poor economic countries,
particularly in parts of Asia and Africa. Pulse crops
harvested for the dry seed rich in protein and other
nutrients. L. sativus is an essential crop in many areas
because it is hardy, drought‑resistant, and can grow in
poor soil conditions. Drought resistance makes L. sativus
a good choice for farmers in regions where other crops
may not thrive. The seeds of L. sativus are also relatively
inexpensive, which means they can provide a low‑cost
source of protein for people. The economically poor
population commonly uses L. sativus pulse to feed
animals. It has been used as boiled preparations (dal),
oil‑based fried preparation (pancake), and salted fried
preparation (pakaudi, bari, chilla, and namkeen).
Since L. sativus pulse price is much less (Rs. 24/‑kg as
compared to Rs 110/‑for other pulses), it is also known
as the pulse of poor. Despite the ban, L. sativus has been
widely sold all over India for primary feeding as a pulse
or adulteration in standard pulses.[29]
Exists as the pulse of the poor
General Sleeman, 1844 gave the rst detailed touching
account of the disease outbreak in Madhya Pradesh in
1831 in his book “Rambles and Recollections of an India
Ofcial.” He has meticulously correlated the disease with
grass pea, drought, and other epidemiological factors.[31]
Is the ban necessary and needs to continue?
Previously, Ethiopia and Bangladesh epidemiological
surveys showed that neurolathyrism occurs only in
the presence of three conditions: extreme poverty of
the grass pea farmers, illiteracy of the consumers,
and availability of grass peas. As it was the cheapest
food during drought‑triggered famines, it is the sole
crop that will survive within the eld, with prolonged
overconsumption as a consequence. The nutritionist has
been learning various medical reports linked through
the ban since 1983 and has found them replete with
loopholes. “Medical test showed that an individual
“might” develop Lathyrism if he ingests 400 g of
L. sativus daily over 3 months or extra. Is such a high
level of consumption possible?” he asks. The Gopalan
Committee report on the thought of which Lathyrus
banned drew on research administered in just 20 villages
in Rewa and Satna districts of Madhya Pradesh.[30]
Existence as a future pulse
L. sativus, commonly known as grass pea, is a pulse crop
cultivated for thousands of years in many parts of the
world, particularly in Africa and South Asia. Despite its
potential as a source of high‑quality protein, its cultivation
and consumption have been limited by the neurotoxin
L‑ODAP, which can cause Lathyrism, a neurological
disease characterized by spastic paralysis. However,
there has been renewed interest in the potential of grass
pea as a future pulse crop, particularly in regions where
climate change and other factors may make cultivating
traditional crops more challenging. Grass pea is a hardy
crop that can tolerate drought, poor soil, and other
adverse conditions, making it well‑suited for cultivation
in marginal areas. Researchers are also working to
develop grass pea varieties with reduced levels of
L‑ODAP, which could allow for its safe consumption as a
food crop. Reduced levels of L‑ODAP involve identifying
and selecting varieties with lower levels of L‑ODAP and
using traditional breeding techniques to develop new
varieties with reduced toxicity. There are also efforts
underway to develop new processing and cooking
methods that can further reduce the levels of L‑ODAP in
grass peas and develop public awareness campaigns to
promote safe consumption practices. Overall, while the
presence of L-ODAP in grass peas presents a signicant
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214 Journal of Preventive, Diagnostic and Treatment Strategies in Medicine - Volume 2, Issue 4, October-December 2023
challenge, there is growing interest in the potential of
this crop as a future pulse, particularly in regions where
traditional crops may face increasing challenges. With
ongoing research and development, it may be possible
to develop new varieties and processing methods
that can allow for this valuable crop’s safe cultivation
and consumption. L. sativus is appreciated for its high
protein content (26%–32%). Further, it has extraordinary
adaptability in extreme conditions, disease resistance
and low input requirement for its cultivation. Despite its
tolerance to drought, L. sativus also does not suffer from
excessive rainfall and may be grown ashore subjected to
ooding, including impoverished soils and heavy clays.
L. sativus is considered to have a high potential to provide
elevated levels of protein, carbohydrates, and minerals
for humans.[32‑36] Further, several new concepts have
emerged during the last three decades that will shape
the future course of L. sativus. No legume other than
L. sativus has ever served as a staple food. Conventional
plant breeding techniques for developing low ODAP
seeds of L. sativus made sufcient progress in the last
few years, but for various reasons, this approach has
remained an unfullled promise.[37]
Nutritional content of Lathyrus sativus
Micronutrient content
L. sativus, like many other legumes, is a good source
of several vital micronutrients. Micronutrients are
essential vitamins and minerals that are required in small
amounts for optimal health and well‑being. Some of the
micronutrients found in L. sativus include:
a. Iron – L. sativus is a good source of iron, an important
mineral for forming red blood cells and transporting
oxygen in the body
b. Zinc – L. sativus is also a good source of zinc, an
essential mineral that is involved in the maintenance
of immune function, wound healing, and cell growth
and division
c. Magnesium – L. sativus contains magnesium,
an important mineral for bone health, energy
metabolism, and nerve function
d. Folate – L. sativus is a good source of folate, a B
vitamin which responsible for the cell growth and
division and particularly important for pregnant
women to prevent congenital disabilities
e. Vitamin C – L. sativus also contains Vitamin C,
an important antioxidant that plays a role in
the maintenance of immune function, collagen
production, and wound healing.
Macronutrient content
L. sativus, commonly known as grass pea, is a legume
that is a good source of several essential macronutrients.
Macronutrients are nutrients the body requires in
relatively higher concentration for the maintenance of
optimal health and well‑being. Some of the macronutrients
found in L. sativus include:
a. Protein – L. sativus is a good source of protein, with
protein content ranging from 20% to 30%, depending
on the variety. Protein is known to be a key factor
for building and repairing tissues, supporting
the immune system, and producing enzymes and
hormones
b. Carbohydrates – L. sativus contains carbohydrates,
which provide energy for the body. The carbohydrate
content can vary depending on the variety and how
it gets prepared
c. Dietary fiber – L. sativus is a good dietary fiber
source, essential for maintaining digestive health and
supporting a healthy gut microbiome. L. sativus ber
content may vary depending on the variety and how
it gets prepared
d. Fats – L. sativus contains a small amount of fat, but it
is generally considered a low‑fat food.
Benets of Lathyrus sativus
L‑ODAP an activator of protein kinase C
There is some evidence to suggest that L‑ODAP,
the neurotoxin responsible for Lathyrism, may act
as an activator of protein kinase C (PKC). PKC is a
family of enzymes involved in signal transduction
and further regulates a large range of cellular
processes (cell proliferation, differentiation, and
apoptosis). PKC activated by various stimuli, including
diacylglycerol (DAG), a lipid signaling molecule, is
produced by the breakdown of phosphatidylinositol
4,5‑bisphosphate (PIP2). Several studies have suggested
that L‑ODAP may act as a structural analog of DAG,
activating PKC. For example, a study published in
“Toxicology and Applied Pharmacology” in 1997 found
that L‑ODAP could activate PKC in cultured rat cortical
neurons. The study also found that the activation of PKC
by L‑ODAP was dependent on the presence of calcium
ions. The activation of PKC by L‑ODAP may contribute
to the neurotoxic effects of the toxin by disrupting cellular
signaling and leading to aberrant cell proliferation and
differentiation.[38] However, the exact mechanism of PKC
activation by L‑ODAP still needs to be fully understood,
and further research is needed to clarify the role of PKC
in the pathogenesis of Lathyrism. Over the last decade,
L‑ODAP has been reported to involve various metabolic
pathways, thereby affecting downstream metabolic
events. Studies reported that PKC activation results in the
cascade of events, such as activation of AMPA receptors,
and some of its downstream effects might be benecial
as in vitro studies with human neuroblastoma cells
showed that L‑ODAP but not D‑ODAP results in nuclear
translocation (stabilization) of hypoxia‑inducible factor‑1
and its stabilization is the primary adaptive response to
lower the oxygen concentrations, which is very crucial
to overcome hypoxic. PKC activators generally possess
potent neurotrophic and neuroprotective properties.[37]
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Journal of Preventive, Diagnostic and Treatment Strategies in Medicine - Volume 2, Issue 4, October-December 2023 215
Homoarginine
Homoarginine is an amino acid structurally similar to
arginine but with an additional methylene group on the
side chain. Some evidence suggests that homoarginine
may have a protective effect against the development
of Lathyrism. It is found that homoarginine reduced
the toxicity of L‑ODAP in cultured rat neuronal
cells and zebrash embryos. The protective effect of
homoarginine against L‑ODAP toxicity may be due to
its ability to compete with L‑arginine for transport into
cells. L‑arginine is a precursor of nitric oxide, vital in
regulating blood ow and vascular function. L-ODAP
has been shown to inhibit nitric oxide production,
which may contribute to the vascular dysfunction
seen in Lathyrism. By competing with L‑arginine for
transport into cells, homoarginine may increase the
availability of L‑arginine and enhance nitric oxide
production, potentially counteracting the effects of
L‑ODAP on vascular function. This Mechanism may also
help explain homoarginine’s protective effect against
other neurological disorders associated with impaired
vascular function, such as stroke and dementia. While
the study’s ndings suggest that homoarginine may
have a protective effect against Lathyrism, further
research is needed to fully understand the mechanisms
of this effect and investigate its potential as a therapeutic
intervention.[37]
Revoke the perception of Lactuca sativa as toxic
crop
Over the course of the past decade, several researchers
have argued that the problem caused by β‑L‑ODAP
in grass pea might have been overstated.[39] In nature,
several toxins are present in commonly used food crops,
but they made manage to eat by correct storage and food
processing procedures. For Lathyrus, the perception of
toxicity as a manageable risk might be more difcult to
achieve, as the crop has been made strongly associated
with famine and disease in the past. This perception
might be removed by its inclusion in more diverse diets
which could help to build a new image of grass pea as
a nutritious functional food, rather than a potentially
toxic food of the poor.
However, the perception of toxicity associated with grass
pea is still hampering the efforts made to improve crop
image. Even if there is no evidence that reduced‑ODAP
varieties of grass pea still pose a risk of neurolathyrism,
changing the thinking of research funding bodies,
breeders, national agricultural authorities and individual
farmers will be a very slow process as long as the toxicity
image of Lathyrus remain persistent.
The main reason behind this is no accurate animal
model yet evidenced the accurate symptoms of human
neurolathyrism by oral consumption of β‑L‑ODAP, as
all existing animal models that show chronic hind leg
paraparesis rely on the injection of β‑L‑ODAP.[40,41] A lack
of a potential animal model, it is difcult to determine
the safe level of β‑L‑ODAP consumption. Further, the
nutritional survey showed the daily consumption of
as much as 2 g of β‑L‑ODAP from grass pea may not
cause any symptoms in humans.[42] However, at present
there is no established threshold stated below which, the
concentration of β‑L‑ODAP in grass pea tissues might
be considered safe.
The need for increased diversity of food production
Around 2500 species of crop plants have been domesticated,
but the vast majority of global food and feed production is
covered by just a small number of crop species. Two‑thirds
of global food calorie production involve just four crop
species: maize, wheat, rice, and soybean. Major crop
species such as these have undergone extensive breeding
in traditional farming systems and more recently in
scientically directed breeding programs. These efforts
have led to vast improvements in crops, particularly
with regard to yield, disease resistance, and geographic
range.[42] The advances made during the green revolution
have allowed global agricultural systems to outpace
the growth in demand for food despite the fourfold
increase in the human population over the course of the
twentieth century.[43] However, during this period, global
food supplies have become more homogeneous, with
increasing reliance on a small number of species supplying
the majority of calories for human nutrition.[44]
To keep up with the rise in global human and livestock
populations, global food, and feed production must
be increased by 100%–110% between 2005 and 2050,[45]
a goal we are unlikely to reach, according to current
trends in crop yields.[46] Currently, a quarter of global
agricultural land suffers from water stress, a gure
that rises to 40% when considering only land under
irrigation. The amount of land suffering water stress
through periodic or chronic drought is likely to increase
over the course of the 21st century due to the effects of
climate change.[47] This means that crops that are able to
deliver high yields under conditions of water stress will
be essential to maintain and increase yields as climate
change progresses. This has made improved drought
tolerance a major objective in crop development by
breeding and genetic engineering.[48]
Newer revelations from our rural observation
study
The pulse was banned for half a century; however, states
have now begun to reconsider the ban on grass peas.
Numerous states such as Maharashtra, Chhattisgarh,
and West Bengal have canceled the ban. The cultivation
of khesari dal was allowed since it was getting used as
animal fodder, but now several studies are challenging
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216 Journal of Preventive, Diagnostic and Treatment Strategies in Medicine - Volume 2, Issue 4, October-December 2023
the concept of linking the dal to Lathyrism. Khesari
has been dubbed because of the poor man’s pulse. The
pulse has a plus point: It grows almost with no effort,
requires minimal water, and grows within 4 months.
A study titled “Study of knowledge, Attitude, and
Practice in Participants with Regular Intake of L. sativus,
But No Spastic Paraparesis” was conducted by clinicians
at the Institute of Medical Sciences, Banaras Hindu
University.[49] The study aimed to determine whether
there was any linkage between Lathyrism and Khesari
Dal, consistent with the study. Nearly 97% of the total
screened population ate up Khesari pulse as their primary
food source, and we did not nd one case of primary
walking difculty. We did nd three cases of poststroke
paralysis, a case of post‑GBS lower limb weakness,
and a case of recurrent myelitis as a neighborhood of
questionnaire‑based study then followed by personally
examining the patients to verify the diagnosis.[49]
Conclusion
With the continuously updated research, the L. sativus
pulse (pulse of poor) crop has moved ahead from the
concept of Lathyrism. Throughout India, L. sativus is a
protein source in various forms (Besan, dal, sweets, and
vegetables). With the updated research, it is clear that
Lathyrism is caused not only by ingesting L. sativus pulse
but it depends by other multi‑factorial conditions, for
example, environmental changes, genetic drift, cultivation
chemicals use, etc., The current research shows that
ODAP, a chemical extract from L. sativus, has medicinal
properties. Further, research on L. sativus ‑ human
interaction is still needed to remove the branding of
L. sativus pulse, a causative agent of Lathyrism. At
present, there is a smaller number of studies available
on Lathyrism’s beneficial characteristics. Moreover,
many cohort studies are required to study the L. sativus
effect (under control doses) on the human population.
Acknowledgments
We would like to acknowledge Institutional Ethical
Committee, IMS, BHU, Varanasi, for approval of the
study. The authors declare that they have no conict of
interest.
Financial support and sponsorship
Nil.
Conicts of interest
There are no conicts of interest.
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