AbstractParkinson’s disease is neurodegenerative disease and no propertreatment or cure has been developed for it till now. Modern researches havefocused on the dietary aspects of Parkinson’s and have revealed that a ketogenicdiet may be beneficial in prevention and for therapy.
This research focuses onthe main dietary elements present in ketogenic diet and their respective rolesin the body with link to Parkinson’s disease. The major constituents present ina ketogenic diet which have neuroprotective effects against Parkinson’s areB-Vitamins, Omega-3 Fatty Acids and Vitamin D. Only a limited amount of beneficialresults have been achieved regarding studies for Vitamin E, Calcium andPotassium. The need for further researches, especially clinical trials for thedifferent constituents of ketogenic diet and their neuroprotective propertiesstill remains.
Introduction Parkinson’sdisease isa progressive disabling neuro-degenerative disease characterized by slow anddecreased movement, muscular rigidity, resting tremor, postural instability anddecreased dopamine transmission to the basal ganglia. It causes memory losswith time and involuntary movements. Increased caffeine intake, young age andsmoking have shown to decrease the incidence of Parkinson’s disease whereas useof pesticides and an increase in the amount of dairy products has shown to increasethe incidence of Parkinson’s. (1) It is more common in men then in women probablybecause of the neuroprotective effect of estrogen. Parkinson’s disease is foundamong 0.3% of the entire population in industrialized countries. (2) It effects 1% of the population of America and Canada over the age of70.
The incidence of disease increases with age and is rarely diagnosed beforethe age of 40 years. (3) About 1% of the populationabove 60 years of age suffers from Parkinson’s.(2) The World Health Organization categorizes prevalence of Parkinson’samong 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 WesternPacific. (4) A study conducted in South-Central India revealed that 28% of thepeople suffering from Parkinson’s lived in urban areas, 10% came fromsemi-urban areas, 50% belonged to rural areas and 12% came from tribal areas. (5) According to a research conducted by Agha Khan University there areestimated to be 6.5 million people suffering from Parkinson’s Disease worldwideout of which approximately 450,000 people are Pakistanis. The study alsorevealed that about a hundred new cases of Parkinson’s are diagnosed every dayin Pakistan.
(6) Another study conducted in Khyber Pakhtunkhwa (KPK) revealed thatprevalence of Parkinson’s Disease in people of KPK according to their age is10% of age 31-40, 10% for 41-50, 23% for 51-60 and 56% for 61-80 therebyshowing that incidence of Parkinson’s is directly proportional to the age i.e.elder people have an increased risk of developing Parkinson’s than youngerpeople. The same study also revealed that 63.
33% patients suffering fromParkinson’s belonged to rural areas whereas 36.67% patients belonged to urbanareas. (7) Thereare several elements linked to the progression and occurrence of Parkinson’sdisease.
Homocysteine tends to play a vital role in the progression of thisdisease. Homocysteine is a sulphur-containing non-protein amino acidthat is a naturally-occurring by-product of the S-adenosyl methionine cycle. (8) Twopathways are employed by the body to maintain Homocysteine levels within anarrow concentration range leaving sufficient Homocysteine to contribute tocellular biochemical pathways yet preventing it from building up toconcentrations that can be deleterious to health. An increase in Homocysteinelevels 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 andprogression of Parkinson’s. Just like other inflammatory diseases, neuro-inflammationalso produces reactive oxygen species (ROS) along with nitric oxide (NO). Themore the production of these inflammatory factors, the more likely the diseaseis to progress.
Phytoestrogens like soybeans, provide estrogen which has provento be neuroprotective in many researchers conducted against Alzheimer’s disease,Parkinson’s Disease and Multiple Sclerosis, etc. estrogen reduces brain damageand improves the survival of neurons by inhibiting the production ofproinflammatory molecules. (10) Thepreventive measure being studied in this particular study, is the role ofKetogenic Diet. Ketogenic Diet is rich in fat, adequate in proteins and low incarbohydrates. The ketone bodies produced during the metabolism of fat act as inhibitoryneurotransmitters, thus causing an anticonvulsant effect on the body. (11) A number of studies have shown the neuroprotective effects ofketogenic diet in neurological disorders. One such study conducted on ratssuffering from Parkinson’s showed that ketogenic diet, being full in ketonebodies, protected the dopaminergic neurons, thereby preventing Parkinson’sand/or slowing down its progression.
(12) Composition of ketogenic diet and its beneficial effects:A number of factors account for Parkinson’s anddiet plays a major role in it along with race, ethnicity, socioeconomic status,age and gender. Ketogenic diet has being gaining popularity with respect toParkinson’s as the diet comprises of elements that can prevent or have atherapeutic effect on Parkinson’s disease. The various dietary elements foundin Ketogenic Diet and their impact on Parkinson’s are discussed below. 2.
1. Vitamin B 2.1.1. Vitamin B-1 VitaminB-1, also known as Thiamin is found in whole-grain, forti?ed, or enriched grainproducts and is commonly known for its energy yielding role in the body i.e. itis a part of co-enzyme Thiamin Pyrophosphate (TPP) which is used in in the conversionof pyruvate to acetyl Coenzyme A.
(13) A deficiency in Thiamin has shown to cause an increase in thedegeneration of dopaminergic neurons as low levels of thiamin disturb thecarbohydrate metabolism which in turn dysfunctions and causes selectiveneuronal damage. The de?ciency also results in metabolic acidosis in the bodyalong with inadequate energy supply to the cerebellar granule cells. (14) 2.1.2. Vitamin B-6 Vitamin B-6 isalso associated with brain health as it assists in the conversion of amino acidTryptophan to Niacin and Serotonin (a neurotransmitter). It is found in meat,fish, poultry, potatoes and other starchy vegetables along with non-citrusfruits, legumes and soy products.
(13) Vitamin B-6has shown to have neuroprotective abilities as it acts as an antioxidant. Apartfrom the antioxidant role, Vitamin B-6 is also used in the synthesis ofdopamine, a neurotransmitter which’s decrease causes Parkinson’s. A studyconducted in Japan revealed that a low intake of dietary Vitamin B-6 but not ofVitamin B-9, Vitamin B-12 and Vitamin B-2, increased the risk for developingParkinson’s. (15) 2.1.3.
Vitamin B-9 Vitamin B-9 iscommonly known as Folate or Folic Acid and is popular among pregnant women forits preventive roles against neural tube defects. It is present in leafy greenvegetables, grains, legumes, liver and fortified cereals. (13) As describedabove that an increase in homocysteine levels is a risk for developingParkinson’s, folate also plays a vital role in keeping homocysteine levelsbalanced. Vitamin B-9 regenerates methionine, an amino acid, from homocysteinein the Methionine – Homocysteine Cycle. (16) Therebykeeping homocysteine levels low or balanced in the body.
Folate also plays arole in the synthesis of different neurotransmitters like serotonin,norepinephrine and dopamine. A deficiency in Vitamin B-9 results in an increasein Homocysteine levels in the body resulting in depression along withslow-progressing neuropathy. (14) 2.1.4.
Vitamin B-12 VitaminB-12 is a water soluble vitamin which is widely known for its roles in new cellsynthesis and maintenance of nerve cells. Its deficiency causes PerniciousAnemia in the body which is characterized by abnormally large and immature redblood 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 inhomocysteine levels.
An increase in homocysteine levels can cause theoccurrence of Parkinson’s in individuals. This happens because an increase inhomocysteine leads to an increase in the levels of a dopaminergic neurotoxin 1-methyl4-phenyl 1,2,3,6-tetrahydropyridine (MPTP), which in turn, kill dopaminergicneurons. (9) Therefore, Vitamin B-12 prevents Parkinson’s indirectly by not lettingthe levels of Homocysteine increase in the body. 2.2. Omega-3-Fatty Acids Omega-3-fattyacids are polyunsaturated fatty acids and are found in fish oils, walnuts, chiaseeds and flaxseeds, etc. The most common ?-3 fatty acids are Alpha-Linolenic Acid(ALA), Docosahexaenoic Acid and Eicosapentaenoic acid (EHA).
Recently a numberof studies have been conducted which revealed the therapeutic effects of ?-3fatty acids in neurological disorders. 2.2.1. Alpha-Linolenic Acid Alpha-LinolenicAcid is found in flaxseed, walnut, wheat germ and canola oils along with nutsand seeds. (13) It isessential for the human body as it cannot be synthesized.
Within the body, ALAis converted to DHA in the liver or in the brain. After being converted intoDHA and even before that, ALA has shown to have neuroprotective effects as itreduces oxidative stress and neuro-inflammation in the body. (17) 2.2.2. Docosahexaenoic Acid DHAis commonly present in fish and fish oils.
(13) Peoplesuffering from Parkinson’s Disease are given Levodopa, a drug, which convertinto Dopamine in the body. Saturated fatty acids hinder this process whereasresearch has shown that polyunsaturated fatty acids like DHA, aid in theprocess and further act as a preventive agent against neuro-inflammation. Italso binds with reactive oxygen species and decreases the oxidative stress onthe body, especially in the brain. (18) 2.
2.3. Eicosapentaenoic Acid EPA are also foundcommonly in fish and fish oils. (13) Theconcentration of EPA in the brain is relatively low as it is catabolized fairlyrapidly 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 deficientin ?-3 fatty acids were more likely to suffer from cognitive defects. (19) 2.3.
Vitamin D Vitamin D is a fatsoluble vitamin which is essential for bone health. It is synthesized in thebody due to sunlight. Among food sources, it is present in liver, fatty fishand their oils, egg yolks, margarine, butter, beef and fortified milk andjuices. (13) Studies haveshowed that people who had a higher level of serum Vitamin D were at a reducedrisk of developing Parkinson’s Disease than those who did not. (20) Another studyconducted in Japan revealed that people with Parkinson’s Disease patients had alower serum Vitamin D level than normal people. (21) Vitamin D alsoplays a neuroprotective effect in the body due to its anti-inflammatoryproperties. (22)Apart fromthat, it is also used to regulate the expression of glial cell line-derivedneurotrophic factor (GDNF), whose administration has been shown to alleviatethe symptoms of Parkinson’s Disease. (23) Another rolethat Vitamin D plays is maintaining the homeostasis of calcium in the blood.
Anincrease in calcium levels can lead to the death of dopaminergic neurons, inturn putting the person at an increased risk of developing Parkinson’s. (22) 2.4. Vitamin E Vitamin E isfamously known for its role as an antioxidant in the human body. It is also afat 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 eightderivatives out of which ?-Tocopherol is the most important when it comes tothe human body. A study revealed that apart from antioxidant properties ofVitamin E, it also exhibited other non-oxidative cytoprotective effects whichmay be beneficial in preventing Parkinson’s.
(24) However, furtherwork needs to be done in order to fully understand the preventive andtherapeutic effects of Vitamin E against Parkinson’s as there is no real promisingstudy or clinical trial which supports this notion. 2.5. Calcium Calcium is amineral which is found in dairy products and is essential for bone health. (13) However, that’snot just where Calcium’s role in the body stops.
It is present in the axon andguards the gateway through which a nerve impulse travels from an axon of oneneuron to the dendrite of another neuron. (25) Glutamate isan excitatory neurotransmitter and when it crosses the synapse it activates ?-amino-3-hydroxy-5-methylisoxazole-4-propionateacid (AMPA) and N-methyl-d-aspartate (NMDA) receptor channels which in turnincrease the concentration of cytoplasmic Ca2+ and in doing so, itindirectly activates the voltage dependent Ca2+ channels. Thiscauses damage to the neurons and ultimately leads to neuronal cell death,therefore high levels of calcium are not advised for people suffering fromParkinson’s. (26) 2.6. Potassium Potassium isanother mineral which is involved in the nerve impulse transmission. It isfound in meats, milks, fruits, vegetables, grains and legumes.
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