A Root Cause Medicine Protocol for Patients With Generalized Anxiety: Comprehensive Lab Testing, Therapeutic Diet, and Supplements

In recent years, the United States has witnessed a concerning rise in stress levels. Compounded by a shortage of mental health providers, this surge in stress has created a pressing mental health crisis, with many individuals struggling to access timely and adequate care. 

In this context, it becomes imperative to recognize and effectively treat anxiety disorders in the primary care setting, where individuals often seek initial assistance for their mental health concerns. 

By enhancing diagnostic capabilities and implementing evidence-based treatment strategies within primary care, healthcare providers can tackle the growing burden of anxiety and improve outcomes for those affected.

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What Is Generalized Anxiety Disorder?

Generalized anxiety disorder (GAD) is a common mental health condition characterized by excessive, persistent worry and anxiety about various aspects of life, such as work, health, family, and everyday occurrences, that occurs most days for at least six months. In the United States, GAD affects an estimated 2.2% of adolescents and 5.7% of adults at some point during their lives. 

GAD is one subset of anxiety disorders, which encompass a range of conditions marked by excessive fear or worry. The anxiety and worry associated with anxiety disorders are characterized by their intensity, persistence, and impairment in daily functioning, which distinguishes them from "normal" anxiety experienced in response to typical life challenges and stressors.

GAD commonly cooccurs with at least one other mental health condition, such as major depression, social anxiety disorder, and panic disorder. For example, 59% of people with GAD also meet the diagnostic criteria for major depressive disorder.

Generalized Anxiety Disorder Signs & Symptoms

The main symptom of GAD is excessive and persistent worry that causes distress and functional impairment. This intrusive anxiety is also often accompanied by physical symptoms, including:

• Restlessness
• Muscle tension
• Sleep disturbances
• Headaches
• Gastrointestinal symptoms
• Shortness of breath
• Heart palpitations and chest pain
• Easy fatiguability 
• Difficult concentration

Root Causes of Generalized Anxiety Disorder

GAD is a complex disorder with an etiology that is not entirely understood. Theoretical models suggest that a combination of factors, ultimately leading to excess oxidative stress, nutrient deficiencies, hormonal imbalances, and immune dysfunction, activate specific brain areas, leading to an inability to stop worrying. 

Nutrient Deficiencies

Nutrient deficiencies can contribute to GAD by affecting the functioning of the brain and the body's ability to regulate stress and mood. Vitamins, minerals, and other nutrients support brain health, neurotransmitter function, and hormone signaling. A lack of these essential nutrients can lead to physiological and chemical imbalances that may contribute to the development or exacerbation of GAD symptoms: 

• B Vitamins (particularly B6, B12, and folate): Vitamin cofactors for synthesizing and metabolizing neurotransmitters. Deficiencies can underlie neurotransmitter imbalances, leading to heightened anxiety.
• Antioxidants and Omega-3 Fatty Acids: Low levels are associated with increased oxidative stress and inflammation in the body (18, 40). Chronic inflammation has been linked to changes in brain chemistry and function, which may contribute to anxiety and other mental health issues.
• Magnesium, zinc, and iron are minerals involved in properly functioning energy metabolism, the immune system, oxygen transport, and neurotransmitter pathways. Deficiencies in these nutrients can lead to reduced energy levels, cognitive impairment, and a decreased ability to cope with stress. 

The Western Diet has been associated with a greater risk for anxiety and other psychological symptoms. This is, in part, likely because this dietary pattern increases systemic inflammation and lacks the essential nutrients required to sustain optimal mental health (27, 31).  

Hormone Imbalances

Various hormone imbalances have been linked to an elevated risk of GAD, including: 

• Thyroid hormones
• Cortisol
• Estrogen, progesterone, and testosterone
• Insulin

Neurotransmitter Imbalances

Lower levels of serotonin, often called the "happy hormone," or reduced serotonin receptor sensitivity may contribute to increased anxiety and mood dysregulation. 

Norepinephrine is associated with the body's "fight or flight" response to stress. Excess norepinephrine can cause physical anxiety symptoms, such as increased heart rate, sweating, and restlessness. 

Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter that helps calm and regulate brain activity. It counterbalances the effects of excitatory neurotransmitters that promote arousal and stress responses. In GAD, a deficiency in GABA may lead to an inability to dampen or regulate anxious thoughts and feelings effectively.

Gut-Brain Axis

The gut-brain axis (GBA) represents the bidirectional communication pathway between the gut and the brain, linking the gastrointestinal system with emotional and cognitive centers in the brain. Emerging research suggests that the gut plays a crucial role in mental health, with disturbances in gut health, such as leaky gut (increased intestinal permeability) and dysbiosis (imbalance in gut microbiota composition), potentially contributing to anxiety and other mood disorders. About 60% of patients with anxiety and depression have some sort of gastrointestinal dysfunction. 

Genetics

Meta-analytical investigations have determined that GAD exhibits moderate heritability, estimated at around 30%. Certain genetic variations affecting processes like digestion, methylation, inflammation modulation, and metabolism can heighten susceptibility to anxiety (55). 

Environmental Factors

Lifestyle and environmental factors significantly impact the onset and progression of GAD. High levels of chronic stress and significant life events can trigger or worsen GAD symptoms, with ongoing stressors like work pressure, relationship difficulties, and bad news playing substantial roles. 

Early life experiences, such as childhood trauma or adverse family environments, can increase susceptibility to GAD by shaping cognitive patterns and coping mechanisms. 

Additionally, the coexistence of anxiety and substance abuse disorders is common, with substance abuse exacerbating anxiety symptoms by disrupting brain chemistry.

How to Diagnose Generalized Anxiety Disorder

An accurate diagnosis of GAD relies on a comprehensive evaluation of the individual's symptoms, medical history, and psychological functioning by a qualified healthcare professional.

Step 1: Use the DSM-5 Criteria

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) provides specific criteria for diagnosing GAD, which include: 

• Excessive anxiety and worry occur more days than not for at least six months
• Worry is difficult to control
• The anxiety and worry are associated with at least three of the following:some text
  • Restlessness or feeling on edge
  • Being easily fatigued
  • Difficulty concentrating or mind going blank
  • Irritability
  • Muscle tension
  • Sleep disturbance (difficulty falling or staying asleep, or restless/unsatisfying sleep)
• The anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
• The disturbance is not attributable to the physiological effects of a substance, another medical condition, or another mental disorder.

The GAD-7 is a validated tool that healthcare providers can administer to screen for GAD, assess the severity of anxiety symptoms, and track changes in symptoms over time. It consists of seven questions that measure the frequency and severity of anxiety symptoms over the past two weeks. Each item is scored on a scale from 0 to 3, with a total score ranging from 0 to 21. Scores of 5, 10, and 15 represent the cutoffs for mild, moderate, and severe anxiety, respectively. 

Step 2: Order Additional Testing to Uncover the Root Causes of GAD

A single test cannot be used to diagnose anxiety; however, specialty testing helps to uncover the biological and physiological imbalances related to anxiety and its associated symptoms.

Hormone & Neurotransmitter Testing

The understanding that hormonal and neurotransmitter imbalances underlie anxiety calls for a comprehensive evaluation of these systems during the initial assessment of GAD. Salivary, urine, and blood tests can assess hormones and neurotransmitters tied to neurological function and emotional processing. The following tests are appropriate to order for patients struggling with GAD: 

• Comprehensive Thyroid Panel w/ Antibodies by Precision Point
• DUTCH Complete (Dried Urine) by Precision Analytical (DUTCH)
• NeuroAdrenal Profile - Random by Doctor's Data
• Insulin, Fasting by Access Med Labs

Micronutrient Analysis

Micronutrient panels are excellent alternatives to single-nutrient biomarkers to comprehensively assess an individual's nutritional status. These panels analyze a range of vitamins, minerals, antioxidants, and other essential nutrients in the body to allow healthcare providers to tailor dietary recommendations and supplementation strategies more effectively, addressing specific nutrient needs based on individual requirements.

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

Gastrointestinal Assessment

Poor gut health can disrupt hormone and neurotransmitter balance, interfere with optimal digestion and nutrient absorption, and contribute to systemic inflammation. A comprehensive stool test measures various markers related to key areas of gastrointestinal health to screen for malabsorption, intestinal inflammation, and dysbiosis. Options include: 

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

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Treatment Plan for Generalized Anxiety Disorder

Living with an anxiety disorder makes daily functioning extremely challenging. Fortunately, an effective treatment plan can ease debilitating worry.

1. Anti-Anxiety Medication

Here's Why This Is Important: 

Medication does not cure anxiety disorders but can help relieve symptoms. By reducing the severity of symptoms, medication can metaphorically "take the weight off a patient's shoulders," making it easier for them to engage in therapy and other interventions aimed at addressing the root causes of their anxiety.

How Do You Do This?

Antidepressant and benzodiazepine anti-anxiety medications are the most common classes of medications prescribed as first-line treatment for GAD. Beta-blockers can be used on an as-needed basis to control the physical symptoms of acute anxiety, such as rapid heartbeat and shaking. (5) 

Lavender oil, often administered in a form called Silexan at 80-160 mg daily, has been shown to have similar efficacy to the benzodiazepine lorazepam when treating adults with generalized anxiety. 

2. Psychotherapy

Here's Why This Is Important:

Psychotherapy, particularly cognitive-behavioral therapy (CBT), is a well-established and evidence-based treatment for GAD. CBT helps individuals identify and challenge irrational or distorted thoughts and beliefs that contribute to anxiety, teaching them more adaptive coping strategies to manage their worries effectively. 

How Do You Do This?

Establish care with a therapist for weekly psychotherapy sessions for at least eight weeks before assessing its effects. Evidence shows that psychotherapy is as effective as medication for GAD and that long-term mental health outcomes are improved when they are used together.

Mindfulness-based therapies, including mindfulness meditation, mindfulness-based stress reduction, yoga, qi gong, and guided imagery, have similar effectiveness to CBT in treating GAD and anxiety-related symptoms (11, 32). 

3. Heal the Gut

Here's Why This Is Important:

Addressing gut health in a GAD treatment protocol is important due to its impact on neurotransmitter function, nutrient absorption, and inflammation. Integrating interventions to foster the GBA alongside traditional treatments can improve outcomes and promote long-term relief from GAD symptoms.

How Do You Do This?

Evidence-based therapies to treat the gut-brain axis focus on dietary and supplemental interventions to reduce intestinal permeability and foster a healthy microbiome. 

Dietary recommendations include consuming a diverse array of whole foods rich in fiber, antioxidants, and polyphenols while minimizing processed foods, refined sugars, and artificial additives (51). Specifically:

• Eat five or more servings of fruits and vegetables daily
• Additionally, add whole grains, nuts, seeds, and beans to your diet
• Restrict added sugars to no more than six teaspoons daily

Specific dietary strategies, such as the Mediterranean or low FODMAP diets, may benefit some individuals with gastrointestinal symptoms. 

Probiotic supplements containing strains such as Lactobacillus and Bifidobacterium have shown promise in improving gut microbiome diversity and reducing anxiety symptoms. Recommended dosages typically range from 10 to 20 billion colony-forming units (CFUs) daily.

Prebiotic supplements, such as inulin or oligosaccharides, can also support the growth of beneficial gut bacteria and improve gut barrier function. Dosages typically range from 2 to 10 grams per day. 

Additionally, the following supplements can help reduce intestinal permeability and inflammation:

• L-Glutamine 5 to 10 grams daily
• Vitamin D 2,000 IU daily
• Omega-3 fatty acids 1 to 3 grams daily
• Zinc carnosine 50 mg twice daily

4. Correct Nutritional Deficiencies

Here's Why This Is Important:

As you heal the gut, patients' nutritional status may inherently improve with better dietary choices and enhanced digestion/absorption. In many cases, doctors may recommend additional supplementation to raise specific nutrients to an optimal level for mental health.

How Do You Do This?

The following vitamins and minerals have been shown to improve anxiety symptoms: 

• Magnesium 300 mg daily (especially when combined with vitamin B6 30 mg daily) (43) 
• Iron 18 mg daily
• Vitamin D 2,000-5,000 IU daily (*short-term courses of higher doses may be necessary to correct deficiency*)
• L-Tryptophan 1-3 grams daily

5. Establish Healthy Lifestyle Habits

Here's Why This Is Important:

Healthy habits form the foundation for mental health. By prioritizing various lifestyle factors, individuals with GAD can improve their mood, reduce stress, enhance their ability to cope with life's challenges, and decrease the need for long-term use of mood-boosting medications or natural supplements.

How Do You Do This?

People with insomnia or poor sleep habits are 17 times more likely to experience anxiety, so it's important to prioritize sleep. These tips can set you up to get a good night's sleep:

• Set a consistent bedtime every day
• If you nap during the day, keep them short and limited to the morning or early afternoon.
• Follow a nightly bedtime wind-down routine
• Dim lights and unplug from electronics at least 30-60 minutes before bed
• Create a bedroom environment that is comfortable and free of distractions

Lack of physical activity can worsen anxiety symptoms; however, maintaining a regular exercise routine has the opposite effect. Studies indicate that any form of exercise is beneficial for alleviating anxiety, with greater benefits observed with the more you do. (47) 

In general, high-fat, high-sugar, and protein-deficient diets are associated with higher levels of anxiety. These food choices can help optimize mental health:

• Add fresh, whole foods like fruits, vegetables, nuts, seeds, and lean animal proteins
• Avoid eating processed foods, refined carbohydrates, and processed meats
• Minimize caffeine intake and swap caffeinated beverages for water or decaf alternatives

The Risks of Untreated Generalized Anxiety Disorder

Untreated GAD can have profound negative consequences on both mental and physical health, which may include:

• Impaired functioning negatively affects performance at work or school, interpersonal relationships, and overall productivity.
• Physical health problems, including cardiovascular disease, gastrointestinal issues, immune dysfunction, and chronic pain conditions.
• Substance abuse
• Depression
• Increased risk of suicide

Generalized Anxiety Disorder Case Study

Read about how one doctor helped a real patient overcome her anxiety here:

Functional Medicine Approach to Generalized Anxiety Disorder: A Case Study

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Key Takeaways:

• By addressing GAD with a comprehensive treatment approach, individuals can experience significant relief from anxiety symptoms and improve their overall quality of life.
• Untreated GAD can lead to impaired functioning, physical health problems, substance abuse, depression, reduced quality of life, and an increased risk of suicide. However, with early recognition and intervention, individuals can receive the support they need to live healthier, happier lives free from the burden of anxiety.