Abstract progressive disabling neuro-degenerative disease characterized by slow

Abstract

Parkinson’s disease is neurodegenerative disease and no proper
treatment or cure has been developed for it till now. Modern researches have
focused on the dietary aspects of Parkinson’s and have revealed that a ketogenic
diet may be beneficial in prevention and for therapy. This research focuses on
the main dietary elements present in ketogenic diet and their respective roles
in the body with link to Parkinson’s disease. The major constituents present in
a ketogenic diet which have neuroprotective effects against Parkinson’s are
B-Vitamins, Omega-3 Fatty Acids and Vitamin D. Only a limited amount of beneficial
results have been achieved regarding studies for Vitamin E, Calcium and
Potassium. The need for further researches, especially clinical trials for the
different constituents of ketogenic diet and their neuroprotective properties
still remains.

 

Introduction

            Parkinson’s
disease is
a progressive disabling neuro-degenerative disease characterized by slow and
decreased movement, muscular rigidity, resting tremor, postural instability and
decreased dopamine transmission to the basal ganglia. It causes memory loss
with time and involuntary movements. Increased caffeine intake, young age and
smoking have shown to decrease the incidence of Parkinson’s disease whereas use
of pesticides and an increase in the amount of dairy products has shown to increase
the incidence of Parkinson’s. (1)

 

It is more common in men then in women probably
because of the neuroprotective effect of estrogen. Parkinson’s disease is found
among 0.3% of the entire population in industrialized countries. (2) It effects 1% of the population of America and Canada over the age of
70. The incidence of disease increases with age and is rarely diagnosed before
the age of 40 years. (3)  About 1% of the population
above 60 years of age suffers from Parkinson’s.(2) The World Health Organization categorizes prevalence of Parkinson’s
among different regions as 0.02% in Africa, 0.22% in America, 0.30% in Europe,
0.03% in South-East-Asia, 0.06% in Eastern Mediterranean and 0.15% in Western
Pacific. (4) A study conducted in South-Central India revealed that 28% of the
people suffering from Parkinson’s lived in urban areas, 10% came from
semi-urban areas, 50% belonged to rural areas and 12% came from tribal areas. (5) According to a research conducted by Agha Khan University there are
estimated to be 6.5 million people suffering from Parkinson’s Disease worldwide
out of which approximately 450,000 people are Pakistanis. The study also
revealed that about a hundred new cases of Parkinson’s are diagnosed every day
in Pakistan. (6) Another study conducted in Khyber Pakhtunkhwa (KPK) revealed that
prevalence of Parkinson’s Disease in people of KPK according to their age is
10% of age 31-40, 10% for 41-50, 23% for 51-60 and 56% for 61-80 thereby
showing that incidence of Parkinson’s is directly proportional to the age i.e.
elder people have an increased risk of developing Parkinson’s than younger
people. The same study also revealed that 63.33% patients suffering from
Parkinson’s belonged to rural areas whereas 36.67% patients belonged to urban
areas. (7)

           

There
are several elements linked to the progression and occurrence of Parkinson’s
disease. Homocysteine tends to play a vital role in the progression of this
disease. Homocysteine is a sulphur-containing non-protein amino acid
that is a naturally-occurring by-product of the S-adenosyl methionine cycle. (8) Two
pathways are employed by the body to maintain Homocysteine levels within a
narrow concentration range leaving sufficient Homocysteine to contribute to
cellular biochemical pathways yet preventing it from building up to
concentrations that can be deleterious to health. An increase in Homocysteine
levels causes an increase in the neurotoxic effect on dopaminergic neurons,
which in turn lead to an increase in cell death. (9)

           

Phytoestrogens also help in prevention and
progression of Parkinson’s. Just like other inflammatory diseases, neuro-inflammation
also produces reactive oxygen species (ROS) along with nitric oxide (NO). The
more the production of these inflammatory factors, the more likely the disease
is to progress. Phytoestrogens like soybeans, provide estrogen which has proven
to be neuroprotective in many researchers conducted against Alzheimer’s disease,
Parkinson’s Disease and Multiple Sclerosis, etc. estrogen reduces brain damage
and improves the survival of neurons by inhibiting the production of
proinflammatory molecules. (10)

            The
preventive measure being studied in this particular study, is the role of
Ketogenic Diet. Ketogenic Diet is rich in fat, adequate in proteins and low in
carbohydrates. The ketone bodies produced during the metabolism of fat act as inhibitory
neurotransmitters, thus causing an anticonvulsant effect on the body. (11) A number of studies have shown the neuroprotective effects of
ketogenic diet in neurological disorders. One such study conducted on rats
suffering from Parkinson’s showed that ketogenic diet, being full in ketone
bodies, protected the dopaminergic neurons, thereby preventing Parkinson’s
and/or slowing down its progression. (12)

 

Composition of ketogenic diet and its beneficial effects:

A number of factors account for Parkinson’s and
diet plays a major role in it along with race, ethnicity, socioeconomic status,
age and gender. Ketogenic diet has being gaining popularity with respect to
Parkinson’s as the diet comprises of elements that can prevent or have a
therapeutic effect on Parkinson’s disease. The various dietary elements found
in Ketogenic Diet and their impact on Parkinson’s are discussed below.

 

2.1. Vitamin B

 

2.1.1. Vitamin B-1

            Vitamin
B-1, also known as Thiamin is found in whole-grain, forti?ed, or enriched grain
products and is commonly known for its energy yielding role in the body i.e. it
is a part of co-enzyme Thiamin Pyrophosphate (TPP) which is used in in the conversion
of pyruvate to acetyl Coenzyme A. (13) A deficiency in Thiamin has shown to cause an increase in the
degeneration of dopaminergic neurons as low levels of thiamin disturb the
carbohydrate metabolism which in turn dysfunctions and causes selective
neuronal damage. The de?ciency also results in metabolic acidosis in the body
along with inadequate energy supply to the cerebellar granule cells. (14)

 

2.1.2. Vitamin B-6

            Vitamin B-6 is
also associated with brain health as it assists in the conversion of amino acid
Tryptophan to Niacin and Serotonin (a neurotransmitter). It is found in meat,
fish, poultry, potatoes and other starchy vegetables along with non-citrus
fruits, legumes and soy products. (13) Vitamin B-6
has shown to have neuroprotective abilities as it acts as an antioxidant. Apart
from the antioxidant role, Vitamin B-6 is also used in the synthesis of
dopamine, a neurotransmitter which’s decrease causes Parkinson’s. A study
conducted in Japan revealed that a low intake of dietary Vitamin B-6 but not of
Vitamin B-9, Vitamin B-12 and Vitamin B-2, increased the risk for developing
Parkinson’s. (15)

 

2.1.3. Vitamin B-9

            Vitamin B-9 is
commonly known as Folate or Folic Acid and is popular among pregnant women for
its preventive roles against neural tube defects. It is present in leafy green
vegetables, grains, legumes, liver and fortified cereals. (13) As described
above that an increase in homocysteine levels is a risk for developing
Parkinson’s, folate also plays a vital role in keeping homocysteine levels
balanced. Vitamin B-9 regenerates methionine, an amino acid, from homocysteine
in the Methionine – Homocysteine Cycle. (16) Thereby
keeping homocysteine levels low or balanced in the body. Folate also plays a
role in the synthesis of different neurotransmitters like serotonin,
norepinephrine and dopamine. A deficiency in Vitamin B-9 results in an increase
in Homocysteine levels in the body resulting in depression along with
slow-progressing neuropathy. (14)

 

2.1.4. Vitamin B-12

            Vitamin
B-12 is a water soluble vitamin which is widely known for its roles in new cell
synthesis and maintenance of nerve cells. Its deficiency causes Pernicious
Anemia in the body which is characterized by abnormally large and immature red
blood cells formation. It is present in animal food sources i.e. meat, fish,
poultry, seafood, milk, cheese, etc. (13) A deficiency in Vitamin B-12 has shown to result in an increase in
homocysteine levels. An increase in homocysteine levels can cause the
occurrence of Parkinson’s in individuals. This happens because an increase in
homocysteine leads to an increase in the levels of a dopaminergic neurotoxin 1-methyl
4-phenyl 1,2,3,6-tetrahydropyridine (MPTP), which in turn, kill dopaminergic
neurons. (9) Therefore, Vitamin B-12 prevents Parkinson’s indirectly by not letting
the levels of Homocysteine increase in the body.

 

2.2. Omega-3-Fatty Acids

            Omega-3-fatty
acids are polyunsaturated fatty acids and are found in fish oils, walnuts, chia
seeds and flaxseeds, etc. The most common ?-3 fatty acids are Alpha-Linolenic Acid
(ALA), Docosahexaenoic Acid and Eicosapentaenoic acid (EHA). Recently a number
of studies have been conducted which revealed the therapeutic effects of ?-3
fatty acids in neurological disorders.

 

2.2.1. Alpha-Linolenic Acid

            Alpha-Linolenic
Acid is found in flaxseed, walnut, wheat germ and canola oils along with nuts
and seeds. (13) It is
essential for the human body as it cannot be synthesized. Within the body, ALA
is converted to DHA in the liver or in the brain. After being converted into
DHA and even before that, ALA has shown to have neuroprotective effects as it
reduces oxidative stress and neuro-inflammation in the body. (17)

 

2.2.2. Docosahexaenoic Acid

            DHA
is commonly present in fish and fish oils. (13) People
suffering from Parkinson’s Disease are given Levodopa, a drug, which convert
into Dopamine in the body. Saturated fatty acids hinder this process whereas
research has shown that polyunsaturated fatty acids like DHA, aid in the
process and further act as a preventive agent against neuro-inflammation. It
also binds with reactive oxygen species and decreases the oxidative stress on
the body, especially in the brain. (18)

 

2.2.3. Eicosapentaenoic Acid

            EPA are also found
commonly in fish and fish oils. (13) The
concentration of EPA in the brain is relatively low as it is catabolized fairly
rapidly by ?- oxidation. People who consume a diet rich in ?-3 fatty acids,
especially EPA, have a very low chance of developing depression or dementia.
Furthermore, a study on children revealed that those whose diet was deficient
in ?-3 fatty acids were more likely to suffer from cognitive defects. (19)

 

 

 

2.3. Vitamin D

            Vitamin D is a fat
soluble vitamin which is essential for bone health. It is synthesized in the
body due to sunlight. Among food sources, it is present in liver, fatty fish
and their oils, egg yolks, margarine, butter, beef and fortified milk and
juices. (13) Studies have
showed that people who had a higher level of serum Vitamin D were at a reduced
risk of developing Parkinson’s Disease than those who did not. (20) Another study
conducted in Japan revealed that people with Parkinson’s Disease patients had a
lower serum Vitamin D level than normal people. (21) Vitamin D also
plays a neuroprotective effect in the body due to its anti-inflammatory
properties. (22)Apart from
that, it is also used to regulate the expression of glial cell line-derived
neurotrophic factor (GDNF), whose administration has been shown to alleviate
the symptoms of Parkinson’s Disease. (23) Another role
that Vitamin D plays is maintaining the homeostasis of calcium in the blood. An
increase in calcium levels can lead to the death of dopaminergic neurons, in
turn putting the person at an increased risk of developing Parkinson’s. (22)

 

2.4. Vitamin E

            Vitamin E is
famously known for its role as an antioxidant in the human body. It is also a
fat soluble vitamin and is found in wheat germ, whole grains, liver, egg yolks,
nuts, seeds, fatty meats and green leafy vegetables like spinach. (13) It has eight
derivatives out of which ?-Tocopherol is the most important when it comes to
the human body. A study revealed that apart from antioxidant properties of
Vitamin E, it also exhibited other non-oxidative cytoprotective effects which
may be beneficial in preventing Parkinson’s. (24) However, further
work needs to be done in order to fully understand the preventive and
therapeutic effects of Vitamin E against Parkinson’s as there is no real promising
study or clinical trial which supports this notion.

 

2.5. Calcium

            Calcium is a
mineral which is found in dairy products and is essential for bone health. (13) However, that’s
not just where Calcium’s role in the body stops. It is present in the axon and
guards the gateway through which a nerve impulse travels from an axon of one
neuron to the dendrite of another neuron. (25) Glutamate is
an excitatory neurotransmitter and when it crosses the synapse it activates ?-amino-3-hydroxy-5-methylisoxazole-4-propionate
acid (AMPA) and N-methyl-d-aspartate (NMDA) receptor channels which in turn
increase the concentration of cytoplasmic Ca2+ and in doing so, it
indirectly activates the voltage dependent Ca2+ channels. This
causes damage to the neurons and ultimately leads to neuronal cell death,
therefore high levels of calcium are not advised for people suffering from
Parkinson’s. (26)

 

2.6. Potassium

            Potassium is
another mineral which is involved in the nerve impulse transmission. It is
found in meats, milks, fruits, vegetables, grains and legumes. (13) Potassium channels
in neurons are highly sensitive to ATP molecules and protect against
neurotoxicity caused by insecticides like rotenone, therefore showing that
Potassium may have even more beneficial effects against neurotoxicity and cell
death and more researches should be conducted to understand its benefits to the
fullest. (27)

 

 

 

 

 

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