Emma M. N. Petshow
Carrie Baldwin-Sayre, ND

Student Scholarship – First Place Case Study

Parkinson’s disease is a neurologic disorder that affects the substantia nigra of the brain by depleting dopamine-secreting neurons.¹ Gastrointestinal distress, including nausea, constipation, and anosmia, are common side effects and early signs of Parkinson’s.² Side effects from Parkinson’s disease medications such as carbidopa-levodopa can also lead to gastrointestinal distress.² Currently, treatment of gastrointestinal distress in Parkinson’s disease is through pharmaceutical management to treat symptoms, as opposed to treating the underlying cause. The most commonly prescribed medications for treatment of constipation are stool-bulking agents such as polyethylene glycol and laxatives, which work to soften the stool, making it easier to pass.³ The symptoms of acid reflux are often treated with a proton-pump inhibitor (PPI) or H₂ blocker.³ Early identification of symptoms associated with Parkinson’s disease, along with proper treatment, can improve quality of life for these patients.

Patient’s Presenting Concerns

A 73-year-old Caucasian female presented to the clinic with chief complaints of constipation and acid reflux. The constipation was subacute and accompanied by generalized lower abdominal pain. The patient reported having a Bristol Stool Scale #2-3 bowel movement every 3 days and straining to pass stool. She denied any blood, mucus, or undigested food in her stool. She also noted acid reflux symptoms for 3 weeks, which had been worsening over the past week with daily constant nausea, a substernal burning sensation, and regurgitation 3 times per day. These symptoms were affecting the patient’s activities of daily living (ADLs).

The patient’s current health concerns were complicated by a recent diagnosis of Parkinson’s disease. This began with anosmia and new-onset resting tremor of the right hand. The patient’s history of restless leg syndrome and her family history of Parkinson’s disease led to a neurology referral and subsequent diagnosis of Parkinson’s disease after DaTscan. Carbidopa-levodopa (25-100 mg tab 3 times daily) treatment was initiated, which produced a mild improvement in tremor but no improvement in anosmia. Her gastrointestinal symptoms appeared to be the latest development of her Parkinson’s disease.

Other pertinent medical history (see Table 1) included diabetes mellitus, chronic kidney disease, hypertension, hyperlipidemia, and breast cancer. The patient has a psychosocial history significant for a 40-pack-year history of smoking (patient quit over 30 years ago), intermittent alcohol consumption, and self-reported decreased sense of purpose in life since being retired. She exercised intermittently but reported that the gastrointestinal symptoms were affecting her ability to keep up with her physical fitness.

Table 1. Pertinent Past Medical History

Condition	Diagnosis	Status
Breast Cancer	1993	Stage 0, left breast, more than 5 mm, no chemotherapy, bilateral mastectomy
Hypothyroidism	1993	Controlled on 100 µg/d levothyroxine TSH 1.8 uIU/mL on 4/18/17
Diabetes Mellitus Type II	2008	Uncontrolled on 5000 mg BID metformin HbA1c 6.8% on 4/18/17
Chronic Kidney Disease	2012	Moderate, Stage 3 GFR 54.2 on 4/18/17
Depression	2012	2000 IU of vitamin D
Anxiety	2013	Controlled with 0.5 mg clonazepam at night Taking 450 mg/d of magnesium citrate
Restless Leg Syndrome	2015	Controlled on 0.25 mg pramipexole nightly
Parkinson’s Disease	2016	Treated with 100 mg carbidopa-levodopa TID
Hypertension	Unknown	Fish oil (unknown dose)
Hyperlipidemia	Unknown	Controlled on 20 mg/d simvastatin Lipid panel on 4/18/17 within normal limits Taking 10 mg CoQ10

(TSH = thyroid-stimulating hormone; GFR = glomerular filtration rate; CoQ10 = coenzyme Q10)

Clinical Findings

The patient had a relatively benign physical exam. Anthropometrics revealed a body mass index (BMI) of 27.32, classifying the patient as overweight. Gastrointestinal exam was positive for moderate, bilateral lower abdomen tenderness and mild, diffuse abdominal tenderness, but was otherwise unremarkable. The patient’s oropharynx was clear, without any signs of erythema. The patient had no signs of anemia. No rectal exam was performed, as the patient did not complain of rectal bleeding and had a recent negative colonoscopy. A 24-hour dietary recall was completed, which was complicated by decreased short-term memory. Analysis of this dietary diary (see Table 2) revealed nutrient deficiencies in terms of total calories per day, servings of fruits and vegetables (currently 0-1 servings per day), total water consumption, and fiber.

Table 2. 24-Hour Dietary Recall

Breakfast	Granola with almond milk
Lunch	Blueberries with mixed nuts
Dinner	Bosnian bread with hot dog topped with onions, mustard, and ketchup
Snacks	Cannot remember snacks
Drinks	“Big Gulp” of diet cola, beer with dinner, and approximately 48 oz of water per day. No coffee.
Food Avoidance	Patient avoids dairy due to “feeling worse” when consuming it. Patient states she intermittently avoids gluten, but drinks beer and eats bread.

See Table 3 for the timeline of the patient’s, continuing through her 4-week follow-up at our clinic.

Table 3. Patient Timeline

Date	Clinical Visit	Diagnostic Workup	Intervention
2/1/16	Initial Visit with PCP: CC: Tremor of hand at rest	Clinical history Complete neurologic exam	Referral to neurologist
9/14/16	Neurology Initial Visit: CC: Resting tremor of right hand and leg PMHx of restless leg syndrome x 1 year on pramipexole No other clinical signs Parkinson’s symptoms	Clinical history Complete neurologic exam which was unremarkable	Repeat exam when the patient is not on pramipexole in 1 month during the late afternoon
10/13/16	Neurology Follow-up: Patient examined without pramipexole prescription for 24+ hours Patient reports mild tingling in toes without any other changes	Clinical history Complete neurologic exam which was unremarkable outside of mild, resting tremor of right lower extremity and hand	Ordered DaTscan at OHSU Ordered labs: SPEP, Immunofixation, Vitamin E (serum), Vitamin B6 (plasma), Copper (serum), BMP
11/15/16	Results of NM Brain DaTscan:	Usual comma-shaped striatal activity was absent. Activity present within both caudate heads, right greater than left, but no uptake was visualized within the region of putamina. This was consistent with striatal dopamine depletion as can be seen in Parkinson’s disease and Parkinsonian syndromes.
11/28/16	Neurology Follow-up: Reviewed DaTscan results, which confirmed idiopathic Parkinson disease	Exam consistent with visit on 10/13/16	Prescribed: carbidopa-levodopa 25-100 mg tab TID
1/10/17	Neurology Follow-up: Patient reported sleep changes and difficulty with medication compliance (on TID dosing) Reported improvement of tremor only 2-3 hours after medication	Exam consistent with visit on 11/28/16	Recommended physical activity including Rock Steady Boxing Referred patient to Dr Tuck, a Parkinson’s disease specialist
4/19/17 5/11/17 5/26/17 7/7/17	Physical Therapy: Goals were to maintain movement and increase energy level	Clinical history and exam without any significant skill deficiencies MiniBest Test score = 21/28	Recommended Rock Steady Boxing and Tai Chi Walking program (2-4 min per day) with strengthening and balance exercises
7/24/17	Initial Visit at NUNM: Constipation and generalized abdominal pain x 3 weeks Symptoms of GERD occurring daily, including constant nausea, 2-3 episodes of regurgitation per day, and substernal burning sensation	Clinical history Complete abdominal exam Screening exam of cardiovascular, respiratory, thyroid, anemia, and peripheral vasculature 24-hour dietary recall Previous record and laboratory studies review	Dietary recommendations Magnesium citrate and probiotic supplementation daily Apple cider vinegar and DGL supplement before meals
7/28/17	1 Week Follow-Up: Constipation resolved Acid reflux: 1-2 episodes per day without regurgitation Constant nausea resolved Compliant with 85% of treatment recommendations	None	Changed DGL to 30 minutes before meals Follow up in 2-4 weeks for symptom check-in
8/21/17	4 Week Follow-Up: Constipation resolved Acid reflux decreased to 1-2 episodes every 2-3 days Compliant with 92% of treatment recommendations	None	No changes needed The patient will follow up in 4 more weeks for dietary counseling

(CC = chief complaint; PMHx = past medical history; SPEP = serum protein electrophoresis; BMP=basal metabolic panel)

Diagnostic Assessment

The diagnoses of acid reflux and constipation were made on a clinical basis. The patient met the symptom, but not the duration of symptom requirement, for the Rome III criteria for functional constipation.⁴ The College of Gastroenterology guidelines states that no laboratory studies and imaging are indicated unless constipation does not respond to treatment.⁵ The patient’s symptoms of acid reflux, including regurgitation, nausea, and retrosternal burning sensation, warranted a diagnosis of gastroesophageal reflux disease (GERD), as clinical symptoms alone can serve as a diagnostic marker.⁶ To further confirm a diagnosis of GERD, an upper endoscopy would be indicated to assess if the patient had concomitant esophagitis or cellular changes; however, this was not warranted due to the subacute nature of her symptoms.⁶

Some challenges involved in evaluating, diagnosing, and treating both acid reflux and constipation in this patient were that they are multifactorial issues with multiple etiologies. The patient’s comorbidities and pharmaceutical medication, specifically carbidopa-levodopa (due to its side effects of nausea and constipation), contributed to her symptoms.² Lastly, a diet with high sugar, low dietary fiber, and decreased water intake could further cause the patient’s gastrointestinal symptoms. Her recent diagnosis of Parkinson’s disease, implementation of carbidopa-levodopa, and dietary changes due to anosmia seemed to be the most likely triggers.

Gastrointestinal symptoms are common with conditions such as Parkinson’s disease.⁷ The prevalence of GERD in patients with Parkinson’s disease was found to be 4.1 times higher than in those without.⁷ One theory involves Lewy bodies causing neuronal degeneration locally in the lower esophageal sphincter, Auerbach’s, and Meissner’s plexus.⁸ Constipation, due to slower transit times in Parkinson’s disease, may present prior to motor symptoms.⁹ Two of the main side effects of carbidopa-levodopa are nausea and constipation.² Levodopa buffers the effect of decreased dopamine production from the substantia nigra region of the brain, and due to its quick absorbency rate, can cause dopaminergic reactions within the local GI tissues.^1,2 Carbidopa mildly decreases the side effect of nausea by not allowing levodopa to be decarboxylated outside of the brain, thereby decreasing dopaminergic effects in the gastrointestinal system.²

The patient’s anosmia led to increased consumption of fried, salty, fatty, and sweet foods due to a decreased sense of smell that resulted in a decreased ability to taste food and flavors.¹⁰ This can lead to a decreased fiber, phytonutrient, and water intake, all of which can cause constipation.¹⁰ Acid reflux symptoms are also exacerbated by consumption of fatty, fried foods.¹¹ Overall, this dietary change is an underlying cause of physiologic dysfunction.

Other diagnoses considered include colon cancer, inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS). The patient had a recent negative colonoscopy, making a diagnosis of colon cancer less likely. Due to the subacute nature of symptoms, she did not meet the criteria for IBD, and her symptoms did not meet the ROME criteria for IBS. There was a high likelihood of complete symptom resolution regarding both constipation and GERD with proper patient compliance; however, the inability to completely remove underlying etiologies of Parkinson’s disease and carbidopa-levodopa could complicate prognosis.

Therapeutic Intervention

To address constipation and acid reflux in this patient with concomitant Parkinson’s disease, a conservative treatment approach was applied using natural remedies. The treatment plan consisted of dietary recommendations, daily supplementation, and symptomatic relief. The most vital component of the patient’s treatment plan were the dietary recommendations with strategies for implementation, described in Table 4.

Table 4. Dietary Recommendations

Dietary Recommendation	Implementation Strategy
1. Increase fruit and vegetable intake to 5-7 servings per day	· Try 1 new vegetable per day · Half of each plate of food should be vegetables · Flavor vegetables with herbs and spices to make them more palatable. Recommended spices include ginger root, basil, oregano, black pepper, turmeric, and curry. · Provided simple vegetable recipes and cooking suggestions to make vegetables taste more appealing
2. Decrease added sugar and simple carbohydrate consumption	· Substitute fruit for sugary snacks · Consume protein at every meal · Eat protein first to induce the satiety signal sooner and feel fuller longer
3. Increase fiber consumption to 30 g per day	· See dietary recommendations #1 and #2 · Consume grains with higher fiber-count, including quinoa, brown rice, and legumes and beans
4. Increase hydration by drinking 64 oz of water per day	· Carry a water bottle · Switch from diet soda to flavored seltzer water

Each dietary recommendation addressed a physiologic etiology related to the patient’s complaints. Recommendation #1 focused on increasing the vitamin, mineral, and phytonutrient content of the patient’s , which is linked to decreased gastrointestinal distress by reducing inflammation and increasing building blocks for healthy metabolism.¹² To increase compliance, healthy recipes were provided that incorporated herbs and spices, which served to increase her ability to taste food. Recommendation #2 was to decrease triggers of gastrointestinal distress, mainly added sugar and simple carbohydrates. Lastly, dietary recommendations #3 and #4 were given to address constipation through increasing fiber and hydration concurrently, which has been found to improve gastric motility.³

The constipation was addressed by magnesium citrate and a probiotic. The patient was taking magnesium citrate at a non-therapeutic dose of 450 mg per day, so the dose was increased to 900 mg per day. Magnesium is as effective in treating constipation as other bulk-forming agents.¹³ A probiotic containing over 5 billion CFUs of a mixture of normal bacterial flora was initiated at 1 capsule per day. Probiotics containing bifidobacteria and lactobacilli are effective at treating underlying gastrointestinal flora dysfunction, improving gut motility, and decreasing constipation.¹⁴

Two natural supplements were initiated to treat the symptoms of GERD. Apple cider vinegar, to assist with digestion, was started at 1-2 tbsp in 1 oz of water 30 minutes before meals. The proposed mechanism is that consumption of an acidic food can increase secretion of gastric acid and digestive enzymes, thereby helping to speed digestion of food and gastric emptying. Patients on carbidopa-levodopa have slower gastric emptying times, increased acid production, and more acid reflux.¹⁵ Deglycyrrhizinated licorice (DGL) was started, as needed, to provide symptomatic relief of dyspepsia; studies have shown it to improve symptoms of dyspepsia by 40% compared to placebo.¹⁶ Although the overall treatment strategy was aimed at addressing dietary dysfunction due to anosmia, not all causes could be removed since part of the etiology included Parkinson’s disease and the medication needed to treat it. Therefore, additional treatments were provided to help the patient have symptomatic relief without severe side effects.

Follow-up & Outcomes

There were several treatment outcome goals for this patient. Within 1 week, constipation should be improved with passage of a single, formed bowel movement daily. The symptoms of acid reflux should also be decreased by 50%, or she should be symptom-free for at least half the day. Within 1 month, the acid reflux should be decreased again by 50%, such that the patient is having only a few flares per day or no symptoms at all. These outcomes represent the ideal scenario, with complete adherence to treatment protocols including dietary recommendations.

Five days after our initial visit, the patient’s constipation had resolved and she was having one Bristol stool scale #4 bowel movement per day without straining. The acid reflux had decreased to 2-3 episodes of regurgitation and nausea per day. The patient was compliant with the magnesium citrate, probiotic, and apple cider vinegar before at least 2 meals per day. Implemented dietary changes included increased vegetable consumption from 0-1 to 3 servings per day, cooking with herbs and spices, and decreased consumption of simple carbohydrates. She was drinking 64 oz of water per day. The patient had not found relief with the DGL while taking it as needed; it was therefore changed to 30 minutes before meals with the apple cider vinegar. The patient exceeded the 1-week treatment expectations with more than 50% improvement of the acid reflux symptoms and complete resolution of constipation. At the second follow-up, 4 weeks after our initial visit, the constipation was still resolved. The acid reflux symptoms had decreased to 1-2 episodes every 2-3 days with continued adherence to the treatment protocol. The patient was happy with the progress of the treatments, and planned to follow up in several weeks for further dietary counseling.

Discussion

Review of the medical literature shows a link between non-motor symptoms of Parkinson’s disease and diet, but there are no current protocols previously studied on dietary interventions to treat these complications. In this case, anosmia led to a dietary dysregulation, which was treated by dietary changes that decreased inflammation, controlled blood glucose, provided the building blocks for neurotransmitters, and decreased transit time for stool (allowing for an increased frequency of bowel movements). For this treatment to be successful, the patient had to be compliant and capable of making dietary changes. Difficulty could arise in patients who could not cook, make food choices, or perform ADLs on their own. It also relies on the physician to provide motivational interviewing to help the patient make the changes needed to implement this treatment strategy.

While the foundational aspect of this treatment plan was vital to lasting cure, patient compliance increased due to quick symptomatic relief. The only study looking at apple cider vinegar and deglycyrrhizinated licorice used together to treat acid reflux found that patients given a gum containing apple cider vinegar, licorice, papain extract, and calcium carbonate had decreased symptoms of acid reflux and nausea compared to placebo.¹⁷ Regarding constipation, there are multiple case reports showing magnesium’s effectiveness in managing constipation; however, more controlled trials comparing it to laxatives or fiber are indicated. Lastly, there is research on probiotics for their ability to increase gut motility in animals, but human model studies need to be conducted to understand their mechanism of action.¹⁴

In conclusion, successful treatment of gastrointestinal dysfunction related to Parkinson’s disease may be achieved with dietary changes and symptomatic relief without using pharmaceuticals. This case report acts as an initial guideline on the implementation of dietary recommendations supplementation to control gastrointestinal complications due to Parkinson’s disease and carbidopa-levodopa. Further research should be done on long-term use of DGL, apple cider vinegar, magnesium, and probiotic supplementation to further evaluate their safety and effectiveness over time as Parkinson’s disease progresses.

References:

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Emma M. N. Petshow is a naturopathic doctoral student and primary medical intern in her final year at the National University of Natural Medicine. She has a passion for women’s medicine, family practice, and sports medicine. She also is a board member of the Naturopathic Medical Student Association, a teaching assistant to multiple courses, and is involved in on-campus research. In her spare time, she coaches a high school track and field team.

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Carrie Baldwin-Sayre, ND, is Associate Dean of Clinical Education for the College of Naturopathic Medicine at NUNM, an attending physician in the NUNM Health Centers, and a clinical assistant professor at OHSU. As President of the Oregon Association of Naturopathic Physicians, Dr Baldwin-Sayre works toward the advancement and recognition of naturopathic medicine. She is a governor-appointed member of the Oregon Health Authority’s Integrative Medicine Advisory Group and is the only ND member of the OHA’s Patient-Centered Primary Care Home Standards committee.