A Functional Medicine Small Intestinal Fungal Overgrowth (SIFO) Protocol: Specialized Testing, Therapeutic Diet, and Supplements

Small intestinal fungal overgrowth (SIFO) is characterized by an overgrowth of fungi within the small intestine. While conventional treatments involving antifungal medications are commonly prescribed, there is growing interest in exploring alternative approaches to manage SIFO. Considering each patient's unique circumstances, a holistic treatment approach to SIFO can reestablish a healthy gut environment, relieve SIFO symptoms, and prevent them from recurring.

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What Is Small Intestinal Fungal Overgrowth (SIFO)?

The mycobiota is a lesser-recognized component of the human microbiome – the microbial ecosystem of bacteria, fungi, archaea, and viruses that live on the skin and all mucosal surfaces of the human body. In a healthy state, fungi live in balance and interact with the immune system to confer health benefits. 

Small intestinal fungal overgrowth (SIFO) refers to the overgrowth of fungus in the small intestine. Research has found that 97% of the fungi associated with SIFO belong to the genus Candida, such as Candida albicans. Candida is a fungus, often called yeast, that usually grows in small amounts in the intestines, skin, mouth, and vagina without causing problems. However, when factors allow Candida, or other fungi, to grow unchecked, this leads to dysbiosis and physical symptoms.

SIFO Signs & Symptoms

SIFO symptoms overlap with other digestive disorders. Studies have shown that around 25% of patients with previously unexplained gastrointestinal (GI) symptoms have SIFO. The most common symptoms associated with SIFO include the following:

• Burping
• Bloating
• Diarrhea
• Gas
• Nausea

When SIFO occurs, it can break down the integrity of the small intestinal barrier. This results in intestinal inflammation and increased permeability, often called a "leaky gut." Not only does a leaky gut magnify uncomfortable GI symptoms, but it also disturbs nutrient absorption and triggers systemic immune responses, inflammation, and the following symptoms:

• Weight loss
• Fatigue
• Joint pain
• Headaches
• Brain fog
• Skin rashes
• Changes in mood

Root Causes of SIFO

Several factors can predispose individuals to develop SIFO.

Impaired immune function, whether due to diseases like HIV/AIDS, diabetes, the use of immunosuppressive medications like steroids, or chronic stress, reduces the body's ability to control fungal growth. This diminished immune surveillance allows fungi to proliferate unchecked in the small intestine.

Broad-spectrum antibiotics can disrupt the balance of the gut microbiome by eliminating beneficial bacteria that compete with fungi for resources. This disruption can create an environment conducive to fungal overgrowth.

Fungi thrive on sugar, and excessive consumption can fuel their proliferation. Eating a diet high in refined carbohydrates and added sugars puts individuals at risk for SIFO.

Conditions that slow down gut motility, such as diabetes-related gastroparesis or chronic opioid use, can lead to stasis of intestinal contents. This stasis provides a favorable environment for fungal overgrowth, allowing fungi more time to colonize and multiply in the small intestine.

Stomach acid normally helps control the growth of ingested pathogens, including fungi. Low acidity, which occurs naturally with aging but can also be caused by proton pump inhibitors (PPIs) or H. pylori infection, can result in a higher fungal load reaching the small intestine, promoting overgrowth.

How to Diagnose SIFO

Here is a step-by-step process for diagnosing this elusive condition.

Step 1: Quantify Fungal Overgrowth 

The gold standard for diagnosing SIFO is a small bowel aspirate, which involves inserting an instrument through the mouth and into the first portion of the small intestine. From there, fluid is collected and analyzed for fungal overgrowth. Given this procedure's cost and invasive nature, alternative testing methods are usually prioritized in the clinical setting to diagnose SIFO. 

The Fungus Related Disease Questionnaire-7 (FRDQ-7) is a tool that was developed to identify individuals at risk for Candida overgrowth. Patients are asked to answer seven questions, and their answers are graded by a point system:

• Score 0-3: unlikely for Candida overgrowth
• Score 4-9: probable Candida overgrowth
• Score 10-21: almost certain Candida overgrowth

Comprehensive stool tests utilize PCR testing and culture to map out the intestinal microbiome, which includes qualifying and quantifying fungal overgrowth. These specialty tests are especially valuable for physicians because they include sensitivity testing for pharmacologic and natural agents against any detected fungi. This sensitivity testing helps guide effective treatment recommendations.

• GI-MAP by Diagnostic Solutions
• BiomeFx by Microbiome Labs
• Microbiomix by Genova Diagnostics

D-arabinitol is a five-carbon sugar metabolite of pathogenic Candida. Elevations measured on urinary organic acid tests indicate fungal overgrowth.

• Organic Acids (OAT) by Mosaic Diagnostics
• Organix by Genova Diagnostics
• Organic Acids Profile by US BioTek 

A serum antibody panel that measures IgA, IgG, and IgM antibodies produced by the immune system in response to a Candida albicans infection can also screen for SIFO caused by Candida albicans. The Candida Profile by Alletess Medical Laboratory is one example of a Candida antibody test. 

Step 2: Labs to Identify the Root Cause of SIFO 

Effective, long-term management of SIFO and prevention of its recurrence relies on identifying and addressing its underlying causes. In cases where the cause of fungal overgrowth is not apparent, additional evaluation is warranted. This may include: 

• Complete blood count (CBC) to screen for immunosuppression
• Hemoglobin A1c (HbA1c) to screen for diabetes
• Thyroid panel to screen for hypothyroidism, which can contribute to intestinal dysmotility
• Helicobacter pylori breath or stool test if low stomach acid is suspected

Step 3: Labs to Personalize SIFO Treatment Plan

Additional tests can aid doctors in assessing overall gut health and constructing holistic SIFO treatment plans. 

A comprehensive stool analysis not only assesses the intestinal microbiome but also measures biomarkers that help diagnose intestinal inflammation, hyperpermeability, and malabsorption that can result from SIFO.

• GI Effects Comprehensive Profile - 3 day by Genova Diagnostics
• GI360 by Doctor's Data
• GI-MAP + Zonulin by Diagnostic Solutions

SIFO shares similarities with and often co-occurs with small intestinal bacterial overgrowth (SIBO), an overgrowth of bacteria in the small intestines. SIBO can be diagnosed with one of these breath tests, which are collected by the patient at home:

• SIBO - 3 Hour by Genova Diagnostics
• trio-smart SIBO Breath Test by Gemelli Biotech
• SIBO/IMO Lactulose Breath Test by Commonwealth Diagnostics International, Inc.

SIFO and leaky gut may cause nutrient malabsorption, so a micronutrient panel can be beneficial to assess the patient's nutritional status. These results will reveal deficiencies or other nutritional imbalances, helping to guide specific dietary and supplemental recommendations.

• Cellular Micronutrient Assay by Cell Science Systems
• Micronutrient Test from SpectraCell Laboratories
• NutrEval FMV by Genova Diagnostics

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Treatment Plan for SIFO

The lab results discussed above set up healthcare providers and their patients for success in treating SIFO. 

1. Treat Fungal Overgrowth

Here's Why This Is Important: 

Treating fungal overgrowth corresponds to a significant improvement in symptom scores (43). 

How Do You Do This?

Standard SIFO treatment is a three-week course of a prescription antifungal medication, such as fluconazole, itraconazole, or posaconazole.

Nystatin is another prescription antifungal that is effective in eradicating fungal overgrowth. Some may prefer it because it is not absorbed into the bloodstream and, therefore, has a lower side effect profile than triazole agents. 

Natural antimicrobials, including oregano, artemisinin, berberine, garlic, and caprylic acid, can be just as effective as their pharmaceutical counterparts by inhibiting the fungal lifecycle, adhesion to the intestinal wall, and biofilm formation.

Another benefit of natural antimicrobials is that they also confer antibiotic properties, which benefit the subgroup of SIFO patients with concomitant SIBO. Research has shown that herbal antimicrobials are as effective as antibiotic therapy for treating SIBO. 

Research also shows that probiotics have an important role in combating SIFO. In one study, Saccharomyces boulardii was as effective as nystatin in reducing fungal overgrowth and resulted in fewer side effects and improved food tolerance. Lactobacillus and Bifidobacterium probiotics also inhibit fungal overgrowth and fungal biofilm formation. 

Limited research supports integrating dietary modifications into a SIFO treatment plan, but preliminary data suggests they may benefit patients with SIFO. For example, a pilot study that evaluated dietary intervention in combination with antifungals for patients with chronic Candida overgrowth concluded that patients who followed the dietary modifications had significantly fewer symptoms three months after treatment compared to those who did not. 

Candida abundance has been found to be positively associated with recent carbohydrate intake and negatively associated with a diet high in fatty acids and proteins (39). Considering these findings, an anti-Candida diet may be beneficial, at least in the short term, for patients struggling with SIFO. Specifically:

• Avoid Sugars: sucrose, fructose, maltose, dextrose, cane sugar, agave, honey, maple syrup, corn syrup, and fruit juice
• Limit Refined Carbohydrates: white bread, white rice, pasta, white rice, breakfast cereals, and baked goods
• Prioritize Non-Starchy Vegetables: spinach, kale, arugula, broccoli, cauliflower, cabbage, asparagus, artichokes, celery, radishes, onions
• Eat Lean Proteins: poultry, fish, eggs, legumes, tofu
• Eat Healthy Fats: avocados, olives, nuts, and seeds

2. Heal the Gut

Here's Why This Is Important:

The gut lining requires time to repair. While eradicating fungal overgrowth addresses the root cause of increased intestinal permeability, doctors may recommend additional supplements to support this healing process and optimal digestion.

How Do You Do This?

Various supplements have been shown to reduce intestinal inflammation and facilitate closing gap junctions between intestinal cells to reestablish a healthy gut barrier. Examples include:

• Vitamin D: 2,000 IU daily
• L-Glutamine: 15-45 grams daily
• Omega-3 fatty acids: 1-3 grams daily
• Zinc carnosine: 50 mg twice daily

Since dysmotility and low stomach acid are two of the strongest modifiable risk factors for SIFO, lifestyle modifications and supplements can be recommended to improve GI peristalsis (muscle contractions that create wake-like intestinal movements) and digestive enzyme secretion. 

• Mindful eating engages the parasympathetic nervous system. Eating in a parasympathetic state encourages healthy digestive enzyme secretions and intestinal muscle contractions required for proper digestion, absorption, and waste elimination. Create a mindful eating environment by setting aside dedicated meal times, minimizing distractions while eating, and engaging all five senses.
• Ginger is a natural prokinetic agent that stimulates gastric emptying and the downward movement of intestinal contents. Many doctors prescribe 500-1,000 mg of ginger nightly before bed. 
• Digestive enzymes, including betaine hydrochloric acid (HCl), can be taken with meals to replace stomach acid in patients with hypochlorhydria. A betaine HCl challenge can help determine the appropriate dose for each meal. 
• Digestive bitters may be considered a natural alternative to digestive enzymes because they stimulate the body's natural secretion of digestive enzymes and improve intestinal blood flow. In addition to foods like arugula, cacao, and radicchio, naturally bitter herbs like gentian, dandelion root, and chamomile can support digestion when taken 15-20 minutes before meals.

3. Address the Root Causes of SIFO

Here's Why This Is Important:

The underlying imbalances predisposing a patient to SIFO must be addressed to prevent future recurrence. 

How Do You Do This?

Many fungi are classified as opportunistic pathogens, meaning they overgrow and cause infection only when the opportunity presents itself. Maintaining a healthy and balanced intestinal microbiome prevents the formation of niches within the intestines, where fungi can grow excessively. 

• A plant-based diet rich in fiber and flavonoids promotes a microbiome characterized by a diverse population of beneficial bacteria. Conversely, Western diets high in ultra-processed foods, added sugars, and unhealthy fats cause dysbiosis.
• Use antibiotics only when indicated, and take them with probiotics to prevent antibiotic-associated fungal overgrowth.
• Counsel patients taking PPIs to discontinue and implement a root-cause treatment protocol to address the medical condition for which the PPI was prescribed.
• Support the immune system by eating an anti-inflammatory diet rich in immune-supportive nutrients, such as vitamins A, C, D, E, selenium, and zinc, and manage stress with mind-body therapies, such as yoga, meditation, and deep breathing.

The Risks of Untreated SIFO

Untreated SIFO perpetuates intestinal inflammation and slows healing, causing chronic GI symptoms associated with irritable bowel syndrome, gastric ulcers, Crohn's disease, and ulcerative colitis (23, 31). 

SIFO Case Study

To learn more about SIFO, read a case study here:

How Sean's Doctor Discovered Candida Overgrowth Was The Root Cause of His Behavioral Outburst: A Case Study

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Key Takeaways:

• Intestinal fungal overgrowth is gaining recognition as an underlying cause of previously unexplained, chronic gastrointestinal issues. Diagnosing SIFO in these patients opens up a new avenue of treatment options to successfully address their digestive symptoms. 
• A comprehensive SIFO treatment plan should encompass eradicating fungal overgrowth, establishing a healthy and balanced intestinal ecosystem, and addressing the root causes of excessive fungal growth. 
• The protocol explained in this article can be used as a template to base effective SIFO treatment protocols in clinical practice.