Nutrition & Gut HealthA/Prof Sanjay Raghav

Gut & Parkinson’s

Parkinson’s & Gut- Recent Interest• Constipation is a highly common complaint among

PD patients. An early clinical manifestation of PD as it can sometimes precede motor symptoms by over a decade.

• Rise in awareness of the role of the gut-brain axis in a number of pathologies has moved PD research towards the study of a possible contribution of the gut to the progression of the disease.

Kim JS, & Sung HY (2015). Gastrointestinal Autonomic Dysfunction in Patients with Parkinson’s Disease. Journal of movement disorders, 8 (2), 76-82

Gut Brain Axis• The gut–brain axis (GBA) is a complex communication network

between gut and brain.

• The central (CNS) and enteric (ENS) nervous systems are communicating through vagus nerve & Prevertebral Ganglia.

• Other pathways are immune activation, intestinal barrier function, and entero-endocrine signaling.

• All these communication lines are bidirectional and involve neuro-immuno-endocrine mediators.

Rhee SH, (2009) Nat Rev Gastroenterol Hepatol 6(5):306–314

Carabotti M, (2015) Annals of Gastroenterol 28:203–209

ENS

• 2nd Brain

• 500 Million Neurons

• 1/200th the number of neurons in the brain(100 Billion)

• Five times as in spinal cord(100 Million)

• Connected to CNS, SNS (Prevertebral Ganglia) &

PNS (Vagus n).

• Autonomosly

Parkinson’s & Gut

• Recently, an increasing amount of evidence has been pointing to the possibility that PD may actually start in the gut.

• Besides the high prevalence of GI symptoms before and during PD development, other findings have supported this view.

• An important finding was that Lewy Bodies – the deposits of alfa-synuclein observed in PD patients – can be found not only in the central nervous system (CNS), but also in the enteric nervous system (ENS) in the gut., even decades before the motor symptoms.

• Studies focusing on Lewy body pathology have actually reported alpha-synuclein deposits in the ENS of nearly every patient with PD.

K. M. Shannon et al. Movement Disorders, vol. 27, no. 6, pp. 709–715, 2012.

Parkinson’s - Does it start from the Gut?

• New evidence strongly suggests that the neuropathological changes in PD may follow a specific chronological and regional pattern.

• Heiko Braak at the University of Frankfurt, Germany, has found that the protein clumps that do the damage, Lewy bodies, also show up in dopamine-producing neurons in the gut.

• In fact, judging by the distribution of Lewy bodies in people who died of Parkinson’s, Braak proposed that it actually starts in the gut, as the result of an environmental trigger such as a virus, and then spreads to the brain via the vagus nerve.

Braak H.Neurobiol Aging.24. 197-211(2003)

Parkinson’s Pathogenesis

• Furthermore, a positive correlation between gut permeability and intestinal levels of alfa synuclein has been observed in patients with early PD.

• The ENS is exposed to ingested toxic substances from the environment, such as pesticides, herbicides and metals, which have all been linked to high levels of alpha-synuclein in the brain and to Parkinsonian symptoms.

Derkinderen P, Shannon KM, & Brundin P (2014).Movement disorders : 29 (8), 976-9

Gut Brain Microbiota Axis

• Recently, the role of enteric flora, or microbiota, has been recognized as a part of the gut–brain axis.

• The gut microbiota can modulate brain function, forming a crucial link in the bidirectional interactions between the intestine and the nervous system.

• Recognition of GBA implies that the GI tract and microbes are involved – either primarily or as secondary effect in neurological/neuropsychiatric disorders.

Microbial Flora

• 100 Trillion. In fact, the number of bacterial cells far outweighs the number of actual human cells.

• Gut flora have around a 100 times as many genes in total as there are in the human genome.

• Weighs about 2-3 Kg

Parkinson's disease linked to gut bacteria

• Dysregulation in the microbiota could lead to factors that are thought to affect Parkinson’s disease.

1. Movement Disorders, 20142 ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, pp. 1-22, 2017.3. Bedarf, J.R., F. Hildebrand, L.P. Coelho, et al. 2017. Genome Med. 9: 1–13.4. Scheperjans, F., V. Aho, P.A.B. Pereira, et al. 2015. Mov. Disord. 30: 350–358

Parkinson’s & Gut Microbes

• In fact, a number of bacterial families significantly altered in PD patients.

• Significant associations between the composition of the gut microbiota and the PD motor symptoms, with bacterial changes correlating with the severity of motor and postural difficulties.

• Recent data suggest abundance of specific bacterial families, together with the severity of constipation, may be highly sensitive and specific diagnostic criteria for PD.

Klingelhoefer L, & Reichmann H (2015). Pathogenesis of Parkinson disease-the gut-brain axis and environmental factors. Nature reviews. Neurology, 11 (11), 625-36

Gut Microbes & PD

• Differences of colonic microbiota and of microbiota metabolism between PD patients and controls. (Bedarf JR et al Genome Med. 2017 Apr 28;9(1):39).

• Probiotics prevent many harmful effects of aging such as decreased neurotransmitter levels, chronic inflammation, oxidative stress and apoptosis-all factors that are proven aggravators of neurodegenerative disease. ( Westfall et al Cell Mol Life Sci. 2017 Jun 22).

• The relative abundance of Enterobacteriaceae was positively associated with the severity of postural instability and gait difficulty. These findings suggest that the intestinal microbiome is altered in PD and is related to motor phenotype.(Scheperjans et al Mov Disord. 2015 Mar;30(3):350-8)

Gut Health

• Prebiotics, probiotics, and dietary modifications, beneficially impacting intestinal barrier integrity, could be effective in PD treatment.

• Manage constipation

Ways to keep your microbiome healthy

• Eating raw fresh vegetables (including juicing carrots, beetroots, spinach)

• Keep your bowels regular- avoid Constipation

• Regularly eating and drinking ‘live’ fermented food and drinks (kefir, kimchi, Kambucha, Sauerkraut)

• Taking good quality probiotics.

• Sufficient Prebiotics (food for gut microbes – natural fibre)

Brewing Kombucha Tea

• Combine hot water and sugar in a glass jar. ...

• Place the tea or tea bags in the sugar water to steep.

• Cool the mixture.

• Remove the tea bags or completely strain the loose tea leaves from the liquid.

• Add starter tea from a previous batch to the liquid.

• Add an active kombucha SCOBY.

Constipation

• Drink Luke warm water.

• Lemon Water

• High Fibre Diet

• Triphala powder

• Exercise & Yoga

• psyllium, (found in products such as Metamucil), is an excellent soluble fiber supplement (Metamucil, Fiberall, Perdiem Fiber

Eating berries may protect against Parkinson’s disease

• High flavonoid content in berries, apples and oranges help ward off the disease. Study participants who consumed the most flavonoids were 40% less likely to develop Parkinson’s.

• Researchers studied 49,281 men and 80,336 women over the course of 22 years and their intake of flavonoids, and analyzed their risk of developing Parkinson’s disease.

Dietary Factors

• No special diets or natural foods have been shown to slow down the progression of Parkinson's disease however diet rich in anti oxidants can be neuroprotective. Berries, Cherries.

• Eating whole grains, fresh fruits, and vegetables is the best approach for any healthy life.

• A diet rich in fruits and vegetables may help protect nerve cell function.

• Many of these foods are also often rich in fiber, which is particularly important for helping to prevent constipation.

Protein

• High levels of proteins may affect how much levodopa can reach the brain and may, therefore, reduce the drug's effectiveness.

• Avoiding protein altogether is not the solution, since malnutrition can result.

• Most doctors recommend trying to maintain a carbohydrate-to-protein ratio of 7:1 throughout the day. This may be difficult to calculate, and some doctors recommend simply keeping proteins to 12% of total daily calories.

• Good control of protein intake may help minimize fluctuations and wearing-off and may allow some patients to reduce their daily levodopa dosage.

• Take your tablets empty stomach.

Dairy foods intake and risk of Parkinson's disease

• PD risk increased by 17% for every 200 g/day increment in milk intake , and 13% for every 10 g/day increment in cheese intake.

• Dairy foods (milk, cheese) might be positively associated with increased risk of PD, especially for men.

Eur J Epidemiol. 2014 Sep;29(9):613-9.

Low Fat Milk & Parkinson’s Disease

• Researchers looked at 25 years of data on almost 81,000 women and 47,000 men, just over 1000 of whom developed the disease.

• The subjects gave details of their consumption of milk, cream, cheese, yoghurt, ice cream, butter and margarine.

• People who drank more than one serving of skimmed or low-fat milk a day were 39 per cent more likely to develop Parkinson’s than those who drank less than one a week.

• Cause- Decrease Urate due to milk proteins, Pesticides.

Caffeine & PD

• Results support previous findings that increased caffeine intake may be associated with a decreased PD risk in men and women

• Gao X J Parkinsons Dis. 2017 Oct 4.

Neuroprotective Treatment

• Coenzyme Q10 (Ubiquinone) . Coenzyme Q10 (also called ubiquinone) is an antioxidant being studied for the treatment of Parkinson's disease. This enzyme is important for cellular energy, which may be impaired in PD.

• However, a high-quality study was unable to demonstrate a benefit for low dosages of this dietary supplement. Not clear whether larger doses given over a long period of time may benefit some patients.

Turmeric – Indian Curry Spice

• It is yellow-pigmented "curry spice" often used in Indian cuisine.

• Turmeric contains curcumin, the polyphenol identified as its primary active component and which exhibits over 150 potentially therapeutic activities, which include antioxidant, anti-inflammatory and anti-cancer properties, Dementia.

• Curcumin crosses the blood-brain barrier and exhibits potent neuroprotective properties.

Curcumin in PD

• Curcumin showed neuroprotective properties in an animal model of Parkinson’s disease; the beneficial effect was thought to be related, in part, to its antioxidant capabilities and its ability to penetrate the brain. Free RadicRes. 2005 Oct;39(10):1119-25

• Curcumin alleviated the effects of glutathione depletion, which causes oxidative stress, mitochondria dysfunction and cell death – and is a feature of early Parkinson’s disease. Free Radic Biol Med. 2008 Mar 1;44(5):907-17

• The c-Jun N-terminal kinase (JNK) signaling pathway is involved in dopaminergic neuronal degeneration, which is in turn associated with Parkinson’s. Curcumin prevents dopaminergic neuronal death through inhibition of the JNK pathway, and thereby offers a neuroprotective effect that may be beneficial for Parkinson’s. Rejuvenation Res. 2010 Feb;13(1):55-64

• Slow-wriggling alpha-synuclein proteins can cause clumping, which is the first step for diseases such as Parkinson’s. Curcumin helps prevent the proteins from clumping. Journal of Biological Chemistry March 16, 2012; 287(12): 9193-9199

Vitamin D & PD

• Low levels seen in various studies.

• Mainly in Early Parkinson’s Disease, in recent studies.

• Not decreasing with progression of disease.

• Arch Neurol. 2011;68(3):314-319.

• Neurology 1997;49 (5) 1273- 1278

• Arch Neurol 2008;65 (10) 1348- 1352

Food As Medicine✓ Fuel your bus✓Make your body a disease

unfriendly environment✓ Key principles

-Avoid problem foods.-Focus on health promoting foods

✓ Plant-based wholefoods diet

Herbal Treatment-Mucuna Pruriens

• Atmagupta/ Velvet Beans/Kapikacchu- climbing legume endemic in India

• Used for PD since 500 BC for Kampavaat

• Levodopa (L-dopa) was first isolated from the seeds of M pruriens in 1937.

• M pruriens grows widely throughout the tropics and is currently mostly planted to improve soil and provide animal feed, and to a smaller extent, for human consumption.

• It is believed the biological purpose of the L-dopa concentration is to protect the plant against insect attack. Mucuna contains larger amounts of L-dopa than any other known natural source.

Mucuna pruriens in Parkinson’s disease: a double blind clinical and pharmacological study-J Neurol Neurosurg Psychiatry 2004;75:1672–1677

• 30 g M pruriens formulation seems to possess potential advantages over existing commercially available controlled release or dispersible formulations of L-dopa in that it combines a rapid onset of action with a slightly longer duration of therapeutic response compared with a dose of standard L-dopa calculated on the basis of the known quantity of L-dopa in mucuna using standard conversion ratios.

• No increase in dyskinesia severity or in peripheral dopaminergic adverse events was found on the mucuna preparation.

• The rapid onset of action and longer on time without concomitant increase in dyskinesias on mucuna seed powder formulation suggest that this natural source of L-dopa might possess advantages over conventional L-dopa preparations in the long term management of PD.

Nutrition & PD

• Drink Plenty of Water

• Avoid Constipation

• Plant based organic diet

• Avoid Dairy products