What is the approach to a protein gap workup?

Protein Gap Workup

A protein gap workup should begin with calculating the difference between actual protein intake (g/kg/day) and recommended requirements, followed by assessment for clinical signs of deficiency, and selective laboratory testing to guide management rather than relying on routine screening. 1

Calculate the Protein Gap

• Determine actual protein intake through detailed dietary assessment, documenting typical protein sources and amounts consumed daily 1
• Calculate current intake in g/kg/day using actual body weight for comparison against recommended levels 1
• Compare against target requirements:
  • Healthy adults: 0.94-1.3 g/kg/day (newer recommendations targeting muscle mass maintenance) 1
  • Older adults and those with increased needs: 1.2-1.8 g/kg/day 1
  • Critically ill patients with obesity: 2.0 g/kg ideal body weight for BMI 30-39.9, up to 2.5 g/kg ideal body weight for BMI ≥40 2

Assess Protein Quality

• Evaluate the balance of essential amino acids in the diet, particularly critical for those consuming primarily plant-based proteins 1
• Consider that animal proteins rank higher in traditional quality metrics due to high digestibility and optimal essential amino acid distribution, while plant proteins may be proportionally low in specific amino acids (grains low in lysine, legumes low in methionine) 2
• Recognize that variety compensates - when diverse plant protein sources are consumed in sufficient quantities, essential amino acid needs can be met without animal protein 2

Clinical Evaluation for Protein Deficiency

• Check for unexplained anemia, edema, and decreased muscle mass as primary clinical indicators 1
• Assess for sarcopenia using standardized measurements of muscle strength and mass 1
• Perform functional testing including handgrip strength and sit-stand tests to evaluate physical function 1
• Clinical evaluation remains the simplest, most widely available, most reproducible method and is satisfactory for the majority of clinical situations 3

Laboratory Assessment (Selective Use Only)

• Measure serum albumin and prealbumin levels, but recognize these are not highly sensitive markers of protein intake adequacy and are affected by inflammation, infection, and underlying disease 1, 3
• Always assess for inflammation (C-reactive protein, ESR) because its presence affects interpretation of all other tests 3
• Consider nitrogen balance studies in specialized settings for more accurate assessment of protein requirements, though this requires accurate 24-hour urine collection and nutritional intake records 1, 2
• Use indirect calorimetry when available to guide protein delivery in critically ill patients with obesity, particularly when combined with urinary nitrogen losses or lean body mass determination 2

Critical Pitfalls to Avoid

• Do not rely solely on serum albumin/prealbumin as markers of protein status, as these are affected by many factors beyond protein intake including inflammation and underlying disease 1, 3
• Do not use routine laboratory testing - the laboratory should be used selectively to complement clinical evaluation, with routine testing relegated to research protocols 3
• Do not overlook increased protein needs during illness, recovery, or in older adults when calculating the gap 1
• Do not ignore protein quality when recommending dietary changes, especially for plant-based diets 1
• Do not forget to account for energy intake, as it impacts protein utilization and nitrogen balance 1

Special Populations Requiring Adjusted Targets

• Critically ill patients: Higher protein delivery (1.3 g/kg adjusted body weight) has been associated with positive outcomes, though anabolic resistance is present 2
• Post-bariatric surgery patients: Considerable gaps exist in understanding protein requirements, with current guidelines based on limited evidence 2
• Kidney disease patients: Adjust to at least 1 g/kg/day for eGFR >30 mL/min/1.73m² and stable; reduce to 0.6-0.8 g/kg/day for eGFR <30 mL/min/1.73m² or declining 1

Management Based on Gap Identification

• Increase total protein intake to meet recommended levels based on individual needs 1
• Distribute protein throughout the day to optimize muscle protein synthesis 1
• Target higher intake (1.2-1.8 g/kg/day) to combat age-related anabolic resistance 1
• Consider leucine supplementation (2.5g) with protein meals to enhance anabolic response 1
• Monitor response through tracking weight and body composition changes, reassessing nutritional status, and adjusting interventions based on clinical response 1