Abstract
A 26-year-old Caucasian woman presented with a two-year history of depression concomitant with irritable bowel syndrome (IBS-C; constipation subtype, gas/bloating). Past evaluation resulted in a clinical diagnosis of IBS-C in August of 2015. Between August and November of 2015, the patient developed worsening bowel irregularities and persistent depression. The patient opted out of conventional treatment and was referred for nutritional care in November of 2017. Throughout one year of treatment with dietary interventions, Chinese herbal medicine, and targeted nutritional supplementation, the patient gradually reached full remission of all complaints.
Introduction
Irritable bowel syndrome (IBS) is the most prevalent gastrointestinal (GI) diagnosis with a world-wide prevalence of 14%1. It is a functional GI disorder characterized by bloating, diarrhea, constipation, abdominal pain, and presents with a high prevalence of psychological comorbidity of depression and anxiety.2 The pathophysiology of IBS is marked by complex interactions between the gut-brain axis which influence the hormonal, immune, and central nervous systems.3 IBS is often multifaceted and can involve many factors such as: psychological stress, intestinal infections, food allergies, as well as intestinal immune-related inflammation and disruption.3 Recent evidence suggests that often inflammation present in the GI tract and the relative increase of cytokines causes oxidative stress leading to damage (through the gut-brain axis) in the hippocampus and amygdala involved in the etiology of mental disorders.3 Small intestinal bacterial overgrowth (SIBO) is one perpetrator of gut inflammation that is associated with IBS, with the most recent meta-analysis showing a prevalence of 31%.4
Though conventional medication exists for IBS, the limited clinical benefit, high medical expense with the possibility of severe side effects, have driven many IBS patients toward alternative medicine such Traditional Chinese Medicine.5 TCM can be easily adjusted in accordance with the individuality of the presentation of known conditions. This is called syndrome differentiation, where every person’s formula will vary and change according to symptoms and/or progress in treatment.5 TCM formulas exert multi-targeted actions including the regulation of hormones and neurotransmitters in the various nervous systems, regulation of the immune response, antimicrobial activity, modulation of motility in the GI tract, modulation of the hypothalamic-pituitary-adrenal (HPA) axis, amelioration of intestinal inflammation and restoration of beneficial microflora.5
We report a case of a 26-year-old woman who simultaneously developed IBS-C and persistent depression. Each condition gradually worsened until stabilizing in severity within four months of symptom onset in August of 2015; with no developing condition clearly preceding any of the other.
Case Narrative
First visit—November 28th, 2017:
The patient had been referred for nutritional and naturopathic care by a friend (has no PCP) in hopes of being able to correct IBS symptoms which she had been suffering from for approximately two years. She mentioned developing depression around the same time period. She used various home remedies (herbs and supplements) found through her own research in an attempt to improve her condition to no avail.
She worked as a waitress for the past five years, lived on her own in an apartment, was single, and had no children. Self-described as “very hygienic and slightly obsessive-compulsive”. She reported no stressful events or infection she could recall prior to the onset of her health problems. Her appearance was unremarkable. There was no discoloration below her eyes or abnormalities in her fingernails. There were no problems concerning the health of her skin. Her tongue, presented with a thick white coating and scalloped edges. Her diet consisted of primarily processed foods that were convenient with minimal preparation, such as cereals, granola, nut bars, fast food (primarily fried chicken and hamburgers), chips, as well as ice cream, pastries and candy.
She described her IBS as symptoms as abdominal pain (primarily in the epigastric and umbilical region), abdominal distention after meals, nausea, acid reflux and intermittent constipation; lasting 3 to 4 days at a time a few times a month. She reported small, hard normal colored stool which were difficult to pass without strain. Acid reflux and early satiety were more prevalent than prior to IBS onset. She always felt cold at room temperature, particularly in her extremities.
She was put on the autoimmune-paleo (AIP, further detailed in the discussion section) diet with the aim of decreasing exposure to common allergens and increasing fiber intake to at least 25 grams per day (from an estimated 10 grams on average currently). It was suggested she limit foods high in fermentable oligo-, di-, monosaccharides and polyols (FODMAP) which may have been contributing toward her condition by exacerbating dysbiosis or small intestinal microbial overgrowth (SIBO). SIBO commonly occurs with presentation of IBS.
She was provided with a hand-out sheet that displayed which foods were considered high and low in FODMAP and advised to ease into the dietary changes over the span of a month. It was suggested she eat 1 to 2 kiwi fruit per day, in the morning, to alleviate constipation. We decided to incorporate a traditional herbal approach concomitantly to hasten her recovery, and through targeted supplementation, ease the depression that may hinder her adherence to the dietary changes needed to experience a sustainable change. She was put on the TCM formula, Si Ni San (3 tablets taken before meals). Using TCM pulse diagnosis, she presented with a wiry pulse in the liver, and a weak-slippery pulse in the spleen position. She was put on a TCM formula, Si Ni San (3 tablets taken before meals).
It was suggested she consider an IgG/IgE food allergen panel to test if she might be reacting strongly to any particular food, as well as a glucose breath test to evaluate the possibility of SIBO. Her resources were limited for testing. She decided she would give a therapeutic trial to the interventions and evaluate progress made.
Follow-up—January 25th, 2018:
She managed to completely transfer to the AIP diet after one month as directed. She was eager to report less distention and constipation, with occurrences only lasting 2 days maximum over the last month. Her depression was moderately improved as soon as 2 weeks after initiating the protocol. She was no longer experiencing coldness in her extremities. Her concern at this point was lingering mild depression, epigastric pain, nausea, acid reflux, indigestion and IBS (albeit the constipation and distention was much improved). On physical examination, it was noticed that the coating on her tongue had become much thinner, now mixed with white and yellow coloration, when previously it was very thick and primarily white.
A multi-vitamin-mineral complex was added once daily to compensate for possible nutrient deficiencies, as the vitamins and minerals included play a role in the digestive process, energy production, and neurotransmitter formation. 200 mg of magnesium glycinate from Pure Encapsulations was added, to be taken once in the morning and once at night, since magnesium deficiency has shown has shown to have an association with depression.17 She was advised to lessen cold foods and raw vegetables and fruit, to reduce loose stools as per TCM dietary guidelines, which presume that raw or cold foods have a tendency to cause loose stool because they are is more difficult to digest than warm cooked food.
It was suggested that she try adding natural probiotics at this stage with homemade or raw sauerkraut bought locally, since she had a source close to her, titrating up from one teaspoon a day to two ounces if tolerated well. Her herbal formula was adjusted by adding Bao He Wan (2 spoonsful before meals, and Si Ni San was reduced to 2 tablets before meals).
Follow-up—March 23, 2018:
She reported that her depression was now practically nonexistent, experiencing it only temporarily for a couple days in the second month prior to her appointment. Her tongue coating was now very thin (normal) and white in color. She reported that her stools have now normalized, no distention, and expressed that her digestion (elimination of nausea, acid reflux, epigastric pain) is almost completely normal again.
After such progress had been made through multiple interventions, it was decided to have her stop the TCM herbs completely to see if her condition remained stabilized on the diet and nutritional supplementation. She was advised to use the first couple of weeks to see if her condition remained stable and if so, consider introducing new foods, preferably only organic whole foods when possible.
Follow-up—July 25th, 2018:
She reported great results, maintaining her state of health with diet and the supplements (multivitamin-mineral and magnesium) alone for the first 3 weeks. She then tried to add in a piece of sourdough bread, which prompted symptoms of abdominal pain and indigestion for roughly a week following this introduction. She was back to maintaining her level of attained health afterwards.
She then added small doses of sprouted oats, lentils, garlic and onions back to her diet with no difficulty over the next 2 weeks. She met another problem upon attempting to introduce Greek yogurt, which provoked a similar response to that of wheat, but with nausea after initially consuming. Similarly, this response calmed down after a few days. It was good to hear that she was able to reintroduce some higher FODMAP foods into her diet without an issue, although we decided she may have an allergy or sensitivity to some wheat and dairy constituents.
At this point it was stated that she may stop taking the vitamins and magnesium to determine if her condition remained stable, and again suggested that testing for allergic reactions might be advantageous at this point. She remained confident that she would be able to figure out what she could eat by diet and reaction alone.
Final appointment—September 27, 2018:
She reported successfully weaning off her multivitamin and weaned down to 100 mg of magnesium glycinate per day. She wanted to remain on this supplement longer out of caution as she believed it would be difficult to get the recommended amount from food. We saw no problem with this low of a dose being sustained unless it provoked bowel irregularities.
She reported no problems with introducing any other whole foods, including nightshades, remaining symptom free at this point, and planned to continue on a diet of whole foods from here on out. She was very proud of how much more energetic and motivated she felt and decided to start school to become a real estate agent. She was congratulated on her progress and concluded our last meeting.
Discussion
Autoimmune Protocol Diet
The AIP diet is a derivative of the original Paleo diet which is an elimination diet modeled after what is assumed humans would have primarily eaten before the agricultural revolution approximately 12 000 years ago.6 Many components of grains, legumes, nuts, seeds, and even raw vegetables are considered “antinutrients”; because these plant compounds, such as phytates, saponins, tannins, lectins, and oxalates can reduce the body’s ability to absorb essential nutrients as well as cause various pathologies through inflammation and damage to the intestinal barrier.6
The AIP diet was chosen due to it being more eliminatory and having positive research outcomes associated with it. The AIP diet has been shown to ease symptoms, reduce inflammation, and sometimes induce complete remission in GI disorders associated with inflammatory bowel disease in human studies.7
The literature has shown an association between intestinal permeability and IBS8, hence an elimination diet was prescribed to remove any foods which may be causing or perpetuating the weakness of the intestinal barrier.
Fructose Malabsorption, IBS, and Depression
Diets high in fructose (have shown to worsen symptoms in IBS patients.9 Clinical trials in humans have shown patients suffering from IBS have a high prevalence of fructose malabsorption, up to 64%.9 Fructose malabsorption is also associated with decreased plasma tryptophan, which may contribute towards depression.9
Fructose malabsorption appears to be, at least partially, modulated by the fructose/glucose ratio of a meal. Glucose reduces fructose malabsorption via the upregulation of the facilitative transporter Glucose Transporter 2 (GLUT2).9 High-fructose corn syrup such as HFCS-55, which is 55% fructose, is found in many soft drinks and was prevalent in this patient’s diet.
Low FODMAP Diet
Several clinical trials have demonstrated the effectiveness of a low FODMAP diet (restriction of fermentable oligo-, di-, monosaccharides and polyols), with a clinical response rate of 50%-80% in patients with IBS.10 Lowering intake of high FODMAP foods, may relieve abdominal distension and visceral hypersensitivity by reducing intestinal fermentation.10 Low-FODMAP diets have also been shown to reduce serum levels of interleukin-6 (IL-6), which is often elevated in IBS and depression.10
Probiotics and Sauerkraut
Lacto-fermented sauerkraut (product we used) has been shown to improve symptoms in IBS patients, in both unpasteurized and pasteurized form.11 This may bring into question how much of the probiotic’s beneficial effect actually came from the metabolite, lactate, produced by Lactic Acid Bacteria (LAB), which may confer a myriad of the health benefits of LAB even when the bacteria has been attenuated by pasteurization.11 Lactic acid has been shown to enhance immunomodulation and may increase enterocyte generation to support intestinal barrier integrity.
Lactate may inhibit excess production of proinflammatory cytokines by modulating lipopolysaccharide-dependent monocyte activation, as well as possibly inhibiting macrophage production of tumor necrosis factor alpha (TNF-α).12 TNF-α has been found in greater amounts in IBS (particularly IBS-C) compared to healthy controls.13
IL-6 is thought to play a vital role in IBS onset as IL-6 activates the transcriptional regulatory protein nuclear factor-κB (NF-kB), which increases intercellular adhesion molecule 1 and plays a key role in the inflammatory response.13 Lactate has been shown to inhibit NF-kB activation.12 This is relevant to depression as IL-6 has been found to be elevated in patients experiencing depression and has been used as a marker for response and prognosis.10 LAB related to sauerkraut in feces (Lactobacillus plantarum and Lactobacillus brevis) were significantly more often present in the intervention group using unpasteurized sauerkraut. Despite the small sample size of this study, lacto-fermented sauerkraut exerted significant improvement on IBS patients’ symptoms and gut microbiota composition. Although we focused on lactate in this discussion, it’s possible that potential prebiotics attributed to the positive effects observed more than viable LAB. Further studies with greater statistical power are needed to clarify which constituents may be most beneficial.
Kiwi
Kiwi has been used as a functional food for constipation. In one study, researchers compared consuming 3 daily whole Zespri kiwi fruit to consuming the 3 Zespri kiwi flesh only in both IBS-C and healthy patients. Both groups had an increase in bowel frequency and reduction in GI symptoms. In IBS-C participants, kiwi consumed whole, significantly decreased the proinflammatory cytokine TNF-α.14
The fiber component of kiwi fruit is 1/3 soluble and 2/3 insoluble which has specifically high-water holding capacity which adds to stool bulking and stimulates a purgative influence.14 The fermentable carbohydrates may change the balance of bacterial species present to more favorable conditions for those who suffer with chronic constipation, through prebiotic and prokinetic effects.14
Magnesium and Depression
Recent data indicates that between 10% to 30% of most populations tested exhibit subclinical magnesium deficiency based on serum magnesium levels < 0.80 mmol/L.17 Currently, approximately 50% of Americans consume the Estimated Average Requirement (EAR) for magnesium.17
Magnesium insufficiency has shown an association with depression and our patient’s previous SAD diet was severely lacking in this mineral.17 Supplementation with magnesium has been shown to decrease, and sometimes ameliorate depression.17
One quintessential role of magnesium is its role as a calcium antagonist and voltage-dependent blocker of the N-methyl-D-aspartate (NMDA) channel which controls the flow of calcium into neuronal cells.17 Depression and magnesium deficiency have an association with systemic inflammation.17 Lack of NDMA inhibition in states of insufficient magnesium availability, causing increased cellular calcium levels, may be a primary mechanism by which magnesium status influences inflammation.17
Traditional Chinese Medicine (TCM) model
Explaining the TCM Dynamics of this case in an “East meets West” fashion may help draw correlation between Western pathophysiology and TCM terminology, enhancing the understanding of our multimodal approach to the client’s GI symptomatology.
Elaborating on the Relationship Between the Stomach, Spleen, and the Liver in TCM
The patient’s first presentation with a wiry pulse in the Liver position, weak and slippery in the Spleen position, tongue distinctions, cold limbs, digestive abnormalities and emotional dysregulation were definite signs of Liver-Spleen disharmony. The thick tongue coating in the Stomach-Spleen area (middle of tongue) signified excess Dampness and Phlegm.
An individual with a deficiency of Spleen Qi may show symptoms of indigestion, gas, bloating, fatigue, as well as a pale or scalloped tongue.19 Irritable bowel syndrome, as well as other functional GI disorders, commonly involve Spleen Qi deficiency.20 Some within the modern TCM community now believe that spleen Qi also represents the collective activity of our gut flora.19 Herbs traditionally said to strengthen the Spleen Qi, such as Astragalus, have been shown to increase Lactobacillus and Bifidobacterium species in animal models.21 The patient complained of OCD like tendencies. Worry and pensiveness is thought to negatively impact the Spleen’s digestive capabilities, which subsequently, can also create stagnation in the movement of Qi.22
The Liver, in TCM, is largely responsible for the free movement of Qi throughout the body.23 The most common factor that impacts the free movement of Liver Qi is emotional disharmony. The Liver is also responsible for Spleen Qi flowing upwards in its right direction.23 Stagnant Liver Qi disrupts the spleen’s ability to transform and transport food and fluids; to “raise the pure essence”.22 When the Liver maintains the free flow of Qi, it promotes the Stomach Qi to descend normally (meaning timely gastric motility of chyme).23
SIBO, Dysbiosis, Hypochlorhydria, Biofilm and Phlegm: East-West correlations
When there is an irregular delay in food transit to the small intestine due to hypochlorhydria (hypochlorhydria is often a symptom of spleen Qi deficiency)23 bacterial counts increase in gastric juice and present increased risks for enteric infections or SIBO.24 The traversing microbes may then protect and propagate themselves through biofilm formation.
Phlegm-Biofilm
By means of biopsy through colonoscopy and gastroscopy; and the photography involved in these procedures, dysbiotic biofilm communities in IBS patients have been found.25 By examining the photography, it can be seen that these dense conglomerations of mucoid matter are actually sovereign entities, attached to the surrounding (healthy) intestinal mucosa, and often have a yellow discoloration.25 These dense biofilm communities may be translated into the category of “damp-phlegm”.
In Western terms, we can think of dampness and phlegm, in order, as a condition of “high humidity” or “stickiness” inside the body.26 Some symptoms can include a feeling of lethargy, water retention, distended abdomen, phlegm discharge, nodular masses, mucus lined bowels and turbidity of fluids.26
Phlegm is a result of dampness which has become dense or solidified through stagnation of Qi and/or through being combined with a drying agent such as pathological “Heat” or “Cold”. The extracellular matrix of pathological biofilms is difficult to penetrate, which is why biofilm-based infections are often antibiotic resistant27 and can be seen as a manifestation of phlegm in TCM. The distinct coloration of the biofilm seen through advanced photographic techniques could help indicate to the modern TCM practitioner whether a pattern of “heat” or “cold” pattern of disease exists in complex cases. This is traditionally translated through tongue and pulse diagnosis.
Heat-Cold Patterns and Tongue Ecology
Heat is associated with a yellow tongue coating and redness, while cold generally presents with a white coating and a pale tongue (under extremely cold conditions it may become a bluish hue).28 The tongue biome shares significant similarity with the gut in microbial diversity.28 The cold or hot syndromes, and progression of such patterns, as well as the cure of said patterns, is associated with a change in the microecology and coloration of the tongue surface.28
Si Ni San (Frigid Extremities Powder)
We chose this formula because it simultaneously strengthens the Spleen and Stomach Qi, disperses Heat, resolves Dampness and Phlegm, nourishes the Liver Blood-yin, as well as increases Qi-blood circulation to relieve Liver Qi stagnation. Si Ni San has also demonstrated wide efficacy in treating a myriad of GI disorders,29 including IBS-C.30
Bao He Wan (Preserve Harmony Pill)
Bao He Wan is used primarily for symptoms that fall under “Stomach Qi Counterflow”, which correlates with symptoms such as acid reflux, nausea, epigastric pain and delayed gastric emptying. It’s traditionally used when one has overeaten for these reasons. In this case, once we resolved most of her Phlegm and coursed the Liver, we still saw remaining symptoms of Counterflow with Heat now revealing itself in the Stomach-Spleen. This was translated by the dense yellow tongue coloration in the part of the tongue that correlates with these organ systems per TCM diagnosis. This formula was then added to Si Ni San.
The medicinal compound Shen Qu was removed from the formula because it contains wheat, and we doubled the dosage of Lian Qiao being used; an herb which has diverse anti-inflammatory and antimicrobial activity, used particularly for rectifying Heat related disorders.31 After thoroughly removing the Heat and remaining dampness (seen through changes in pulse and tongue diagnosis), her remaining symptoms resolved.
Limitations
Since this is personalized medicine, even if one was to follow this exact protocol, there is no guarantee the treatment would produce the same outcome in a different, unique patient. This was a motivated patient who had no major problems adhering to the treatment plan; a relationship where the patient was not as motivated and inconsistent in following the treatment protocol could lead to a different result.
Due to a lack of financial resources for testing, there might have been factors involved which we may not have been aware of, such as possible chronic GI infections, as well as hypersensitivities or allergies to the foods that provoked a negative response upon reintroduction. The amalgamation of each integrative therapy, as well as the ability of the patient to recognize sensitivity to particular foods on their own, all contributed to this patient’s positive outcome.
Conclusion
We have reported a case of a multimodal treatment approach for a patient with IBS, depression, that led to a sustainable elimination of this common comorbidity. Chinese herbal medicine along with evidence based dietary and nutritional interventions for depression, anxiety and IBS, is effective in the clinical setting.
Summary of Formulas Chosen
| Si Ni San | |
| 7:1 concentrated extract in a 750mg caplet | |
| Ingredients Per Dosage | |
| Bai Shao (Radix Alba Paeoniae) | 750 mg |
| Chai Hu (Radix Bupleuri) | 562.5 mg |
| Zhi Shi (Fructus Immaturus Aurantii) | 562.5 mg |
| mix-fried Gan Cao (Radeix Glycyrrhizae) | 375 mg |
| TCM Indications | |
| 1. Nourish Liver Blood | |
| 2. Soften the Liver | |
| 3. Spread Liver Qi | |
| 4. Strengthen the spleen | |
| 5. Resolve Dampness | |
| Bao He Wan | |
| 7:1 concentrated extract in granules | |
| Ingredients Per Dosage | |
| Shan Zha (Fructus Crataegi) | 530 mg |
| Ban Xia (Rhizoma Pinelliae) | 265 mg |
| Fu Ling (Poria) | 265 mg |
| Chen Pi (Pericarpium Citri Reticulatae) | 100 mg |
| Lai Fu Zi (Semen Raphani) | 100 mg |
| Lian Qiao (Fructus Forsythiae) | 180 mg |
| TCM Indications | |
| 1. Food stagnation | |
| 2. Harmonize the stomach | |
| 3. Resolve damp-heat (with modification) in the middle burner (stomach and intestines) | |
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