Abstract:
Introduction:
Patients with poor nutritional status prior to surgery are more likely to suffer complications after surgery including infection and death, have a greater hospital length of stay and cost of hospitalization, and are more likely to be readmitted to the hospital within 30 days after surgery.1 But malnutrition is one of the few readily modifiable preoperative risk factors. In the context of the changes produced by the stress response to surgery and injury, we determined that 5 essential ingredients are needed to overcome the nutritional deficits specific to surgery. These 5 supplements (Bromelain, Hydroxymethylbutyrate, NADH, Vitamin D, Zinc) support energy production, strengthening of muscles, immune function, and response to pain. Therefore, we compared surgical recovery characteristics in patients treated with these nutritional supplements versus standard of care.
Methods:
In a prospective randomized trial, we assigned participants undergoing foot surgery (ingrown toenail and wart removal) to NutraHeal™ (NH), NutraHeal Plus™(NHP), or standard of care (C) from 1 week prior to surgery and 3 weeks after surgery. NutraHeal™ is a nutritional supplement that contains 7.5 micrograms (300 IU) of Vitamin D3, 7.5 mg of Zinc, 600 mg of Hydroxymethylbutyrate, and 45 mg of Bromelain. NutraHeal Plus™ is a nutritional supplement that contains 7.5 mg of Zinc, 600 mg of Hydroxymethylbutyrate, 45 mg of Bromelain, and 7.5 mg of reduced Nicotinamide Adenine Dinucleotide (NADH).2 Patients randomized to standard of care did not receive any of the ingredients in NutraHeal™ or NutraHeal Plus™. Acute wound healing was evaluated at 1 and 3 weeks after surgery using a Likert rating scale against expected results from −4 (much worse) to +4 (much better) including the expected reference grade of zero (0). Patients also completed the PROMIS-29 instrument to assess pain interference, depression, physical function, social function, fatigue, anxiety, and sleep at baseline, day of surgery (DOS), and at 1 and 3 weeks after surgery. The raw scores from these domains were rescaled into a standardized T-score; a change of more than 3 points on the T-score was considered significant. Linear regression modeling was also applied adjusting for age, gender, and the interaction between age and randomized group.
Results:
Between August 29, 2022, and February 24, 2023, 46 patients were randomized to NH (n= 15), NHP (n=15), or C (n=16). All patients underwent ingrown toenail removal. The average age of the study population was 50.5 ± 18.5; average BMI was 35.7 ± 8.2; 63% were female; 2% were African American; 30% were current smokers; 26% had hypertension; 9% were diabetic; 4% had coronary artery disease; and 4% had atrial fibrillation. Three patients withdrew from the study and three were lost to follow-up leaving 40 patients in the final analyses. Patients in the control group were younger (C: 44.7 ± 18.3; NH: 55.9 ± 18.5; NHP: 56.2 ± 17.5), and healthier - less likely to have a history of smoking (C: 6.3%; NH: 36.4%; NHP: 42.9%; p=0.07), hypertension (C: 13.3%; NH: 45.5%; NHP: 28.6%), diabetes (C: 6.7%; NH: 9.1%; NHP: 14.3%), coronary artery disease (C: 0%; NH: 7.1%; NHP: 9.1%), and atrial fibrillation (C: 0%; NH: 0%; NHP: 14.3%). Overall wound healing at 3 weeks was better in NH (Likert rating = 2.7) and NHP (Likert rating = 2.4) patients compared to control patients (Likert rating = 1.1). Wound healing scores also declined from 1 to 3 weeks after surgery in the control patients (Likert rating = -2.3) compared to both NH (Likert rating = -0.1) and NHP (Likert rating = -0.1). From baseline to 3 weeks after surgery, pain interference (-3.6 vs -2.9) and anxiety (-3.4 vs -1.2) decreased in the NH group compared to C. Pain interference also decreased (-4.1 vs -2.9) while fatigue (-4.1 vs -3.1) improved in the NHP group compared to C. Between DOS to 3 weeks after surgery, fatigue (-5.7 vs -3.1), pain interference (-4.5 vs -2.0) and sleep (-6.0 vs -3.0) were better in the NH group compared to C. Between 1 and 3 weeks, pain interference (-6.6 vs -2.5) decreased in the NH group compared to C while physical (3.2 vs 2.2) function and sleep (-3.1 vs 1.5; p=0.04) were better. Linear regression modeling revealed an interaction between age and randomized group such that older patients receiving NH had better sleep at 3 weeks (p=0.059). Adverse events were experienced by 4 patients and were minor (rash, nausea). Patient satisfaction with the supplements and wound healing at 3 weeks after surgery were rated as “good” (scale: excellent, good, moderate, inadequate, unsatisfactory).
Conclusions:
NH and NHP improved wound healing at 3 weeks after surgery. NH decreased pain interference and anxiety while improving sleep. NHP decreased pain interference and fatigue. Continuing NH and NHP for 3 weeks after surgery appears to better maintain healing and patient-reported health status, and more so with aging. Nutritional supplements in NH and NHP targeting preservation of muscle function, energy production, wound healing, pain, and immune function support recovery after surgery.
Keywords:
- Nutritional Supplements
- Wound Healing
- Pain Interference
- Surgical Recovery
- Immune Function
