What causes severe nausea and fatigue?

Causes of Severe Nausea and Fatigue

Severe nausea and fatigue occurring together require systematic evaluation for cancer-related causes, medication effects, metabolic abnormalities, gastrointestinal disorders, and environmental toxin exposure, with cancer-related fatigue being the most extensively studied cause when these symptoms co-occur in oncology patients.

Cancer-Related Causes

Cancer and its treatments are among the most common causes of severe combined nausea and fatigue, affecting up to 80% of patients receiving chemotherapy or radiotherapy 1. Cancer-related fatigue (CRF) is defined as "a distressing, persistent, subjective sense of physical, emotional and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning" 1.

• Fatigue rarely occurs in isolation and most commonly presents with other symptoms including nausea, pain, distress, anemia, and sleep disturbances in symptom clusters 1.
• Patients perceive fatigue to be more distressing than nausea and vomiting, though both significantly impact quality of life 1.
• In patients with metastatic disease, the prevalence of cancer-related fatigue exceeds 75% 1.

Medication and Treatment Effects

Chemotherapy-induced nausea and vomiting has a major impact on quality of life and commonly co-occurs with fatigue 1. Multiple medication classes can cause both symptoms:

• Opioid analgesics cause nausea, vomiting, and fatigue through central nervous system effects 1, 2.
• Metoclopramide, commonly used to treat nausea, paradoxically causes fatigue and drowsiness as adverse effects in many patients 2.
• Combinations of narcotics, antidepressants, antiemetics, and antihistamines may contribute to excessive drowsiness and increasing fatigue 1.
• Cardiac medications such as β-blockers may elicit bradycardia and subsequent fatigue 1.

Metabolic and Nutritional Causes

Imbalances in electrolytes and nutritional deficiencies commonly cause both severe nausea and fatigue 1:

• Imbalances in sodium, potassium, calcium, iron, and magnesium serum levels are often reversible and may reduce both symptoms with appropriate supplementation 1.
• Hypercalcemia can cause nausea, vomiting, and fatigue 1.
• Anemia significantly contributes to fatigue and should be evaluated 1.
• Nutritional intake may be affected by nausea, vomiting, loss of appetite, mucositis, and bowel obstruction, creating a vicious cycle 1.

Gastrointestinal Disorders

Chronic gastrointestinal conditions frequently present with both nausea and fatigue 3:

• Gastroparesis causes delayed gastric emptying with chronic nausea and associated fatigue 3.
• Gastric outlet obstruction or bowel obstruction causes nausea and vomiting that can lead to dehydration and fatigue 1.
• Gastroesophageal reflux and gastritis contribute to chronic nausea 1.
• Constipation, occurring in approximately 50% of patients with advanced cancer, can worsen both symptoms 1.

Environmental and Toxin Exposure

Heavy metal exposure is an often-overlooked cause of severe nausea and fatigue 4:

• Lead poisoning causes fatigue through impaired oxygen transport from elevated intracellular calcium levels and eryptosis 4.
• Manganese toxicity initially induces non-specific symptoms including fatigue, headache, irritability, and muscular pains 4.
• Aluminum exposure alters erythrocyte morphology and induces eryptosis, leading to anemia and subsequent fatigue 4.
• Consider heavy metal testing when fatigue presents with environmental exposure risk factors such as contaminated water or soil, especially when accompanied by cognitive changes, headaches, or peripheral neuropathy 4.

Neurologic and Vestibular Causes

Central nervous system disorders can cause both symptoms through different mechanisms 5, 6:

• Acute migraine headaches commonly present with nausea and fatigue 6.
• Vestibular disturbances cause nausea and associated fatigue 6.
• Conditions that increase intracranial pressure typically cause neurologic signs in addition to nausea 7.

Endocrine and Metabolic Conditions

Pregnancy is the most common endocrinologic cause of nausea and must be considered in any woman of childbearing age 7:

• Early pregnancy commonly causes both severe nausea and fatigue 6.
• Numerous metabolic abnormalities including thyroid disorders can cause both symptoms 7.

Infectious and Inflammatory Causes

Acute gastrointestinal infections and food poisoning are the most common causes of acute nausea and vomiting, often accompanied by fatigue 8:

• Most infections are self-limiting and require minimal intervention 7.
• Viral syndromes commonly cause both symptoms 6.

Psychiatric and Functional Disorders

Psychiatric diagnoses including anxiety and depression can manifest with both nausea and fatigue 7:

• Anxiety-related nausea may respond to benzodiazepines 1.
• Functional disorders without identifiable organic cause can present with chronic symptoms 3.

Critical Evaluation Approach

When evaluating severe nausea and fatigue together, prioritize the following assessments 1, 5:

• Review all current medications including over-the-counter, herbal, vitamins, and supplements, as medication interactions may contribute to worsening of both symptoms 1.
• Assess for dehydration and electrolyte abnormalities requiring immediate correction 9.
• Evaluate nutritional status including caloric intake, protein levels, and micronutrient deficiencies 1.
• Screen for anemia with complete blood count 1.
• Consider comprehensive metabolic panel to identify reversible causes 1.
• Assess for alarm symptoms requiring urgent evaluation including severe dehydration, altered mental status, or signs of obstruction 5, 6.

Common Pitfalls

• Failing to recognize that fatigue is often under-reported by patients who assume they must live with it or fear treatment alterations 1.
• Overlooking heavy metal toxicity as a cause, particularly when exposure has been chronic and low-level over years 4.
• Not considering medication adverse effects and interactions as primary causes before extensive workup 1.
• Treating nausea aggressively with medications that themselves cause fatigue, such as metoclopramide, without considering this trade-off 2.