Naturopathic Treatment of Gastrointestinal Dysfunction in the Setting of Parkinson’s Disease

Abstract

Parkinson’s disease is associated with multiple nonmotor symptoms including gastrointestinal (GI) distress, which affect patients’ activities of daily living and are traditionally treated by pharmaceutical agents aimed at symptom control. In this case, a 73-y-old female presented with 3 wk of constipation and acid reflux after a recent diagnosis of Parkinson’s disease and initiation of carbidopa-levodopa 6 mo prior. A contributing factor was anosmia leading to a vast dietary change. All other etiologies were excluded via clinical history and physical exam. Dietary intervention was initiated as the foundational treatment and included increased consumption of vegetables to 5 servings per day, increased dietary fiber to 30 g per day, increased protein consumption, decreased sugar consumption, and increased hydration. These dietary changes were accompanied by symptomatic relief of acid reflux through apple cider vinegar and deglycyrrhizinated licorice as well as probiotic and magnesium citrate initiation for constipation. The patient had complete resolution of constipation and 50% improvement in acid reflux after 5 d and complete resolution of all symptoms after 1 mo. GI complications associated with neurologic disorders such as Parkinson’s disease may be managed via foundational dietary changes with natural symptom control with similar outcomes as pharmaceutical management but without lasting side effects.

Introduction

Parkinson’s disease is a common neurologic disorder that affects the substantia nigra of the brain by depleting dopamine-secreting neurons.¹ Although this disease is most commonly associated with dementia, bradykinesia, and resting tremor, gastrointestinal (GI) distress including nausea, constipation, and anosmia are common side effects and early symptoms and sometimes are the first signs of Parkinson’s disease.² The side effects from Parkinson’s disease medications, such as carbidopa-levodopa, can also lead to GI distress.² Currently, treatment of GI distress in the setting of Parkinson’s disease is done primarily through pharmaceutical management to treat the symptoms versus the underlying cause. The most commonly prescribed medications for treatment of constipation are fiber-bulking agents such as Miralax and laxatives, which work to soften the stool making it easier to pass.³ The symptoms of acid reflux are often treated with a PPI or H₂ blocker such as omeprazole or ranitidine.³ Identification and early intervention of these symptoms associated with Parkinson’s disease and proper treatment can provide patient’s improved quality of life and regain some sense of control. This case was written following the CARE guidelines.⁴

Presenting Concerns

A 73-year-old Caucasian female presented to the National University of Natural Medicine (Portland, OR, USA) campus clinic with a chief complaint of constipation and acid reflux. The patient does not have a history of any GI disease, history of similar symptoms, and had not sought medical treatment for this issue in the past. The constipation was subacute and had been occurring for 3 weeks accompanied by generalized lower abdominal pain. The patient reported having a bowel movement every 3 days and straining to pass stool. Her bowel movements were described as ranging from a 2 to 3 on the Bristol stool scale, and the patient denied any blood, mucus, or undigested food in her stool. She also noted acid reflux symptoms for 3 weeks, worsening during the past week with daily, constant nausea, burning sensation in the chest, and regurgitation 3 times per day. These symptoms were starting to affect the patient’s activities of daily living, including her daily workout regimen and dietary intake.

The patient’s current health concerns were complicated by a past medical history that includes a recent diagnosis of Parkinson’s disease in October 2017. The neurologic complaints began with anosmia several years ago, which led to the patient changing her diet from one including fruits and vegetables to one with increased sugar and salt due to it being all she could taste. This lead to a dysregulation of her blood glucose with a recent HbA_1C of 6.8% in April 2017. The patient had a previous diagnosis of restless leg syndrome treated by pramipexole but noted a new onset right hand resting tremor in February of 2016. The new onset tremor, anosmia, history restless leg syndrome, and family history of Parkinson’s disease in her maternal grandmother led to the patient being evaluated by a neurologist and ultimately diagnosed with Parkinson’s disease after the results of a DatScan. The patient has been controlled on Carbidopa-Levodopa 25- to 100-mg tab TID since with mild improvement in tremor, but no improvement in anosmia. Her GI symptoms appeared to be the latest symptom of her Parkinson’s disease either through direct causation from neurologic decline or due to the dietary change associated with anosmia, although an isolated acute episode could not be ruled out.

Other pertinent concomitant medical history includes diabetes mellitus type 2, chronic kidney disease stage III, hypertension, hyperlipidemia, and breast cancer with bilateral mastectomy listed in Table 1. The patient also has a psychosocial history significant for a 40 pack-year history of smoking (patient quit more than 30 years ago), intermittent alcohol consumption, and self-reported decreased sense of purpose in life since being retired. She exercises intermittently with a friend doing water aerobics but reports the GI symptoms are affecting her ability to keep up with her physical fitness schedule.

Table 1.

Patient Timeline

Date	Clinical Visit	Diagnostic Workup	Intervention
02/01/16	Initial visit with PCP: CC: Tremor to hand at rest.	Clinical history. Complete neurologic exam.	Referral to neurology.
09/14/16	Neurology initial visit: CC: Right hand and leg with resting tremor. PMHx of restless leg syndrome × 1 y on pramipexole. No other clinical signs of symptoms of Parkinson’s disease.	Clinical history. Complete neurologic exam which was unremarkable.	Repeat exam when the patient is not on Pramipexole in 1 mo during the late afternoon.
10/13/16	Neurology follow-up: Patient examined without Pramipexole prescription for 24+ h. Patient reports mild tingling in toes without any other changes.	Clinical history, complete neurologic exam which was unremarkable outside of mild resting right lower extremity and hand tremor.	Ordered DatScan at OHSU. Ordered labs: SPEP, Immunofixation, vitamin E, Vitamin B6, Cu, BMP.
11/15/16	Results of NM brain DatScan.	Usual comma-shaped striatal activity is absent. Activity present within the right greater than left caudate heads, but there’s no uptake visualized within the region of putamina, consistent with striatal dopamine depletion as can be seen in Parkinson’s disease and Parkinsonian syndromes.
11/28/16	Neurology follow-up: Reviewed the results of the DatScan, which confirmed idiopathic Parkinson’s disease.	Exam consistent with visit on 10/13/16.	Prescribed: Carbidopa-Levodopa 25-100 mg tab TID
01/10/17	Neurology follow-up: Patient reports sleep changes and difficulty with mediation compliance (on TID dosing). Reports tremor is improved only 2 to 3 h 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.
04/19/17 05/11/17 05/26/17 07/07/17	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/d) with strengthening and balance exercises.
07/24/17	Initial visit at NUNM: Constipation and generalized abdominal pain x 3 wk. Symptoms of GERD occurring daily including constant nausea, 2 to 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-h dietary recall. Previous record and laboratory studies review.	Dietary recommendations. Magnesium citrate and probiotic supplementation daily. Apple cider vinegar and DGL supplement before meals.
07/28/17	1-wk follow-up: Constipation resolved. Acid reflux 1 to 2 episodes per day without regurgitation. Constant nausea resolved. Compliant with 85% of treatment recommendations.	None	Changed DGL to 30 min before meals. Follow up in 2-4 wk for symptom check-in.
08/21/17	4-wk follow-up: Constipation resolved. Acid reflux decreased to 1 to 2 episodes every 2 to 3 d. Compliant with 92% of treatment recommendations.	None	No changes needed. The patient will follow up in 4 more wk for dietary counseling.

Clinical Findings

The patient had a relatively benign physical exam. Vital signs were within normal limits outside of prehypertension, which is consistent with the patient’s history. Anthropometrics revealed a body mass index of 27.32 kg/m², which classifies the patient as overweight, but there is no significant weight loss or gain during the past 6 months. GI exam was positive for moderate tenderness to the bilateral lower abdomen with mild diffuse abdominal tenderness but was otherwise unremarkable. Other exams performed included cardiovascular, pulmonary, and thyroid, which was also within normal limits except for mild expiratory wheezes bilaterally consistent with a recent acute bronchitis that the patient was treated by her primary care provider. The patient’s oropharynx was clear without any signs of erythema or edema. 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 colonoscopy on file from her primary care provider.

A 24-hour dietary recall was completed, which was complicated by decreased short-term memory issues per patient. The dietary diarrhea is listed in Table 3.

Table 3.

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 coke, beer with dinner, and approximately 48 oz of water per day. No coffee.
Food Avoidance	Patient avoids dairy due to “feeling worse” when consuming. Patient states she intermittently avoids gluten, but drinks beer and eats bread.

Analysis of this diet leads to significant nutrient deficiencies including total calories per day, servings of fruits and vegetables (currently 0 to 1 servings per day), total water consumption, and fiber.

Diagnostic Assessment

The diagnosis of acid reflux and constipation was made on a clinical basis. The patient met the symptom requirement for the Rome III criteria for functional constipation due to reporting straining during bowel movements, lumpy hard stools (Bristol stool scale 1 to 2), and a decrease in stool frequency of fewer than 3 bowel movements per week.⁵ The patient reported symptoms for only 3 weeks, which the Rome III criteria requires 3 months of symptoms for an official diagnosis of functional constipation.⁵ There were no symptoms that could suggest an acute, emergent condition including blood in stool, recent weight loss, family history of colon cancer or irritable bowel syndrome (IBD), anemia, or acute onset of constipation.⁶ Due to lack of alarm signs with chronic constipation in an older adult, the College of Gastroenterology guidelines states that no laboratory studies and imaging are indicated unless if constipation does not respond to treatment.⁷ The patient’s symptoms of acid reflux including regurgitation, nausea, and retrosternal burning sensation warrant 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, but was not warranted due to subacute nature of symptoms.⁷

Some challenges involved in evaluating, diagnosing, and treating both acid reflux and constipation in this patient is that they are both multifactorial issues with multiple etiologies. The patient’s concomitant conditions of diabetes mellitus, hypothyroidism, chronic renal insufficiency, and Parkinson’s disease all can contribute to the symptoms the patient is presenting with as well as the patient’s prescription medication, specifically carbidopa-levodopa (Sinemet), which has nausea and constipation and primary side effects.² Last, the patient’s diet was poor with high sugar, low dietary fiber, and decreased water intake, which can further cause the symptoms of constipation and acid reflux. Due to these multiple confounding factors, a single causation is unable to be identified, but many of these etiologies have related pathophysiologic effects. Of all the potential causes of the patient’s symptoms, her recent diagnosis of Parkinson’s disease, implementation of Sinemet anti-Parkinson’s medication, and dietary change due to anosmia seem to be the most likely triggers.

GI symptoms including those of acid reflux and constipation are common with neuromotor conditions such as Parkinson’s disease.⁸ The prevalence of GERD in patients with Parkinson’s disease was 4.1 times higher than those without.⁸ Although no direct causation exists, one theory involves Lewy bodies causing neuronal degeneration locally in the lower esophageal sphincter, Auerbach’s, and Meissner’s plexus.⁹ Constipation related to Parkinson’s disease due to slower transit times as well as Parkinson’s medication such as Sinemet and may come before the motor symptoms associated with Parkinson’s disease.¹⁰ Levodopa acts as a dopamine replacement, buffering the effect of decreased dopamine production from the substantia nigra region of the brain.¹ Two of the main side effects of this medication are nausea and constipation.² The purposed mechanism of action is Levodopa has a quick absorbency rate and can cause dopaminergic reactions within the local GI tissues.² Carbidopa decreases the side effect of nausea mildly by not allowing Levodopa to be decarboxylated outside of the brain, therefore decreasing dopaminergic effects in the GI system.² The benefit of Sinemet is short lived however, and many patients find that it increases their nausea.

Another contributing factor involves the patient’s anosmia leading to increased consumption of fried, salty, fatty, and sweet foods. A loss of sense of smell can lead to decreased ability to taste food and flavors.¹¹ This dietary change contributed to the patient’s symptoms as she had decreased fiber intake, decreased phytonutrient intake in the form of fruits and vegetables, and decreased water intake, all of which can cause constipation.¹¹ The increased consumption of fatty, fried foods can cause symptoms of acid reflux and exacerbate it.¹² Overall, this dietary change is an underlying cause leading to physiologic dysfunction.

Other diagnoses considered include colon cancer, IBD, and IBS. The patient had a recent colonoscopy, which was negative, and she is not reporting blood in stool. Therefore, a diagnosis of colon cancer is less likely, but a repeat colonoscopy is indicated at the proper timeline or sooner if the patient develops any concerning symptoms or does not respond to treatment. She does not meet the criteria for IBD or IBS because symptoms have not been occurring long enough and her symptoms do not meet the ROME criteria for IBS. With a proper diagnosis and implementation of a treatment program, there is a high likelihood of complete symptom resolution regarding both constipation and GERD. The inability to completely remove underlying etiology both Parkinson’s disease and Sinemet prescription may 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 foundational support surrounding dietary recommendations, daily supplementation to address constipation and GERD, and symptomatic relief.

The most vital component of the patient’s treatment plan was the dietary recommendations. Without dietary changes, the patient’s symptoms would only be controlled instead of addressing the cause. After review of a 24-hour dietary recall was done in office, dietary recommendations were given to the patient 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 one new vegetable per day. Half of each plate of food is vegetables. Flavor vegetables with herbs and spices to make them more palatable. Spices recommended 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 specific physiologic reason related to the patient’s complaints. Dietary recommendation number 1 focused on increasing the vitamin, mineral, and phytonutrient content of the patient’s diet, which is linked to decreased GI distress through decreasing inflammation and increasing building blocks for healthy metabolism.¹³ To increase patient compliance, healthy recipes were provided, aimed at incorporating herbs and spices, which will increase her ability to taste food. The second recommendation’s goal was to decrease triggers of GI distress, mainly added sugar and simple carbohydrates and had a secondary treatment purpose of addressing uncontrolled diabetes mellitus. High-sugar diets and diets more carbohydrate heavy are associated with GI inflammation causing constipation, dysbiosis, and sugar dysregulation; by swapping fruits for sugars and consuming more protein, the patient can decrease these undesirable effects. Last, dietary recommendations 3 and 4 were given to address constipation. Studies have shown that increasing dietary fiber and hydration concurrently can be used to treat constipation because it improves gastric motility.³ The dietary changes alone could resolve the symptoms the patient was experiencing, but other treatment mechanisms were put into place in the meantime as lifestyle change takes time.

The constipation was treated with magnesium citrate and a probiotic. The patient was already taking magnesium citrate at a nontherapeutic dose of 450 mg per day, which was increased to 900 mg per day. Magnesium has been shown to be as effective in treating constipation as psyllium and other bulk-forming agents.¹⁴ A probiotic containing more than 5 billion colony-forming units of a mixture of normal bacterial flora including Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus rhamnosus, Lactobacillus plantarum, Bifidobacterium lactis, Lactobacillus salivarius, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus brevis, and Streptococcus thermophiles was initiated at 1 capsule per day. Probiotics have been studied in literature as effective in treating underlying GI flora dysfunction specifically bifidobacteria and lactobacilli, therefore improving gut motility and decreasing constipation, but more studies are needed to show a direct link.¹⁵

Although the GI tract is healing and the patient is making dietary changes, 2 natural supplements were brought on board to treat the current symptoms of GERD. Apple cider vinegar was recommended to assist with digestion at a dose of 1 to 2 tbsp in 1 oz of water 30 minutes before meals. No studies have been conducted testing the effectiveness of apple cider vinegar as a treatment for symptoms of GERD. The purposed mechanism behind apple cider vinegar before meals is that consumption of an acidic food can increase gastric acid and therefore digestive enzymes providing the necessary tools to digest a meal and increase gastric emptying. Patient’s with Parkinson’s disease on Sinemet therapy have increased gastric emptying times, leading to acid reflux and increased acid production.¹⁶ By prepping the stomach with the necessary tools to digest a meal, the goal is to speed the gastric emptying time and allow the body’s natural gastric acid to do its job without causing pathology. In conjunction with apple cider vinegar, deglycyrrhizinated licorice (DGL) was recommended to provide symptomatic relief of dyspepsia on an as needed basis as studies have shown it to be effective in improving symptoms of dyspepsia by 40% compared with placebo.¹⁷

Overall the treatment strategy was aimed at addressing one of the causes of the patient’s symptoms her dietary dysfunction due to anosmia, but not all causes could be removed because part of the etiology includes 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 and Outcomes

With strong adherence to the treatment guidelines and dietary changes recommended, there were several treatment outcome goals. Within 1 week constipation, should be improved with patient passing a single, formed bowel movement daily. In addition, within 1 week the symptoms of acid reflux should be decreased by 50% to half the day that patient is without symptoms. Within 1 month, the acid reflux symptoms should be decreased by 50% again where the patient is having only a few flares per day or no symptoms at all. These outcomes represent the ideal scenario with 100% adherence to treatment protocols including dietary recommendations.

At the first phone follow-up with the patient, 5 days after our initial visit, her constipation had resolved and she was having one, Bristol stool scale 4 bowel movement per day without straining. The acid reflux symptoms had decreased from constant nausea with multiple episodes of regurgitation per day to only 2 to 3 episodes of regurgitation and nausea only occurring with the regurgitation now, no longer constant. The patient was compliant with the double dose of magnesium citrate, daily probiotic, and apple cider vinegar before most meals (most meaning at least two meals per day). The patient had made some dietary changes including a half a plate of vegetables per day, increased from 0 to 1 servings per day to 3 servings per day. She also had been cooking with more herbs and spices as well as decreased consumption of simple carbohydrates. She was drinking 64 oz of water per day. The patient had not found any relief with the DGL taking it as needed for symptom relief. She did not have any adverse events. The DGL was changed to 30 minutes before meals with the apple cider vinegar. The patient had exceeded the 1 week treatment expectations with more than 50% improvement of the acid reflux symptoms and complete resolution of constipation.

At the second phone follow-up with the patient, 4 weeks after our initial visit, she continued to not report any issues with bowel movements. The acid reflux symptoms had decreased to 1 to 2 episodes every 2 to 3 days with continued adherence to the treatment protocol. The patient was happy with the progress of the treatments with the plan to follow up in several weeks for further dietary counseling.

Discussion

Review of the medical literature shows a link between nonmotor symptoms of Parkinson’s disease and diet, but there are no current recommendations or protocols previously studied on specific dietary interventions to treat these complications. In this case, the patient had a recent dietary change due to anosmia, which was the initial Parkinson’s disease symptom. The dietary changes made by the patient decreased inflammation, controlled blood glucose, provided the building blocks for neurotransmitters, and increased transit time for stool. Although the changes treated the underlying cause of the GI dysfunction, the patient had to be compliant with the dietary changes and capable of making them for this treatment to be successful. Difficulty could arise in a patient with more severe Parkinson’s disease that affected their ability to cook, make food choices, or perform ADLs on their own. It also relies on the physician to provide motivational interviewing to help the patient want to make the dietary and behavioral changes needed to implement this treatment strategy.

Although 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 decreased nausea compared to placebo.¹⁸ There have been no studies considering the use of these treatments before a meal as a preventive dose. Regarding constipation, there are multiple case reports showing magnesium’s effectiveness in managing constipation, but more double-blind placebo controlled trials comparing it to laxatives or fiber are indicated to truly test its effectiveness. Last, there is research on probiotics for their ability to increase gut motility in animals, but more needs to be done in human models to understand the mechanism of action.¹⁵

In conclusion, successful treatment of GI 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 dietary recommendations as well as supplementation to implement to control GI complications due to Parkinson’s disease and Sinemet. 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 with time as Parkinson’s disease progresses.

Table 2.

Pertinent 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 mcg levothyroxine TSH 1.8 uIU/mL on 04/18/17
Diabetes mellitus type 2	2008	Uncontrolled on 5000 mg BID metformin HbA1c 6.8% on 04/18/17
Chronic kidney disease	2012	Moderate, stage 3 GFR 54.2 on 04/18/17
Depression	2012	2000 IU of vitamin D
Anxiety	2013	Controlled with 0.5 mg clonazepam at night taking 450 mg of magnesium citrate
Restless leg syndrome	2015	Controlled on 0.25 mg pramipexole nightly
Parkinson’s disease	2016	Treated with 100 mg Sinemet TID
HTN	Unknown	Fish oil (unknown dose)
HLD	Unknown	Controlled on 20 mg simvastatin lipid panel on 04/18/17 within normal limits Taking 10 mg CoQ10

Abbreviations: HTN, hypertension; HDL, high-density lipoprotein; CoQ₁₀, coenzyme Q10.

Biographies

Emma M. Neiworth-Petshow, ND(c), is a primary medical intern and naturopathic doctoral candidate at the National University of Natural Medicine, Portland State University, in Portland, Oregon.

Carrie Baldwin-Sayre, ND, is the associate dean of clinical education and physics at the National University of Natural Medicine, Portland State University, a clinical assistant professor at Oregon Health and Science University, and the president of the Oregon Association of Naturopathic Physicians.