Oral Nutritional Interventions

Oral Nutritional Interventions

PEP Topic 
Fatigue
Description 

Oral nutritional interventions involve the provision of dietary advice or education with or without dietary modification or nutritional supplements. Nutritional supplements included in this type of intervention are those involving general protein-calorie supplements and multiple combinations of vitamins, minerals, and other compounds. Specific herbal supplements and some highly specific supplements such as carnitine and individual vitamins are considered as separate interventions.

Effectiveness Not Established

Systematic Review/Meta-Analysis

Baldwin, C., Spiro, A., Ahern, R., & Emery, P.W. (2012). Oral nutritional interventions in malnourished patients with cancer: A systematic review and meta-analysis. Journal of the National Cancer Institute, 104, 371–385.

doi: 10.1093/jnci/djr556
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Purpose:

STUDY PURPOSE: To examine the effect of oral nutritional interventions on outcomes among patients with cancer

TYPE OF STUDY: Meta-analysis and systematic review

Search Strategy:

DATABASES USED: MEDLINE. EMBASE, CINAHL®, Scopus, AMED, CANCERLIT, ERIC, Scopus, ISI Web of Science, and Cochrane Collaboration, 1998–2010
 
INCLUSION CRITERIA: RCT; adults with cancer judged to be malnourished or at risk for malnutrition; comparison of nutritional interventions with usual care. 

Literature Evaluated:

TOTAL REFERENCES RETRIEVED: 44,073
 
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Study quality was evaluated according to criteria established and the Cochrane handbook. All studies were determined to be at risk of bias from one or more characteristics related to randomization and blinding to treatment allocation.

Sample Characteristics:

  • FINAL NUMBER STUDIES INCLUDED = 13 in systematic review, 9 included in meta-analysis
  • TOTAL PATIENTS INCLUDED = 1,414
  • SAMPLE RANGE ACROSS STUDIES: 31–358
  • KEY SAMPLE CHARACTERISTICS: Various tumor types receiving adjuvant or neo adjuvant chemotherapy or radiotherapy

Phase of Care and Clinical Applications:

  • PHASE OF CARE: Active anti-tumor treatment 

Results:

Six studies compared dietary advice with routine care, three evaluated oral nutritional supplements, and seven compared dietary advice and oral supplements with usual care. Some studies included samples that were not malnourished, although all were at risk according to definitions established in the studies. Findings from meta-analysis showed high heterogeneity among studies. Results with studies causing the high heterogeneity removed were:
  • QOL and Functional Scales on EORTC: no significant effects 
  • Fatigue: no significant effects
  • Dyspnea: mean difference = –2.9 (95% CI [–4.0, –1.8], p < .001) (six studies)
  • Loss of appetite: mean difference = –2.35 (95% CI [–4.48, –0.22], p = .03) (seven studies)
  • There was no effect seen on survival and effects on body weight and energy intake was inconsistent.

Conclusions:

Analysis indicates that oral nutritional interventions were associated with significant improvement in dyspnea and appetite symptom scales. It is unclear what the specific impacts of dietary counseling versus oral nutritional supplements were on these outcomes.

Limitations:

  • Few studies retained in meta-analysis that addressed high heterogeneity.
  • Outcomes analyzed were based on only single-item scales on the EORTC.
  • Patients varied from those receiving adjuvant treatment to those receiving palliative care treatment.
  • Varied length of follow-up from three weeks to two years.

Nursing Implications:

Nutritional interventions such as dietary counseling and oral nutritional supplementation may be helpful in managing symptoms of dyspnea and anorexia in patients cancer. Evidence does not provide strong support due to variability in timing of interventions, the exact nature of the interventions, actual nutritional status of patients included, and the timing of outcome data measurement. Nutritional interventions such as dietary counseling and oral nutritional supplement are low-risk interventions that may be helpful for some patients. Well-designed research and reporting in this area would be helpful to guide practice.

Research Evidence Summaries

Cerchietti, L. C., Navigante, A. H., Peluffo, G. D., Diament, M. J., Stillitani, I., Klein, S. A., & Cabalar, M. E. (2004). Effects of celecoxib, medroxyprogesterone, and dietary intervention on systemic syndromes in patients with advanced lung adenocarcinoma: a pilot study. Journal of Pain and Symptom Management, 27, 85–95.

doi: 10.1016/j.jpainsymman.2003.05.010
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Intervention Characteristics/Basic Study Process:

  • Medroxyprogesterone (MPA) 500 mg twice daily (BID) + celecoxib 200 mg BID + polymeric diet X 6 weeks
  • Enteral food supplementation = 20% ​basal metabolic rate (BMR) with meal advice to caregiver and patient advice to engage in regular exercise.

Systemic-immune metabolic syndrome (SIMS) implies dysregulation of psychoneuroimmunoendocrine homeostasis, resulting in cachexia, anorexia, chronic nausea, early satiety, fatigue, tumor fever, cognitive changes, and superinfections (i.e., increased cytokines may increase cachexia-anorexia syndrome [CAS] and mediate anorexia).

Sample Characteristics:

The study included 15 adult outpatients with stage IIIb or IV lung adenocarcinoma.

Patients were included if they 

  • Had CAS 10% weight loss
  • Had anorexia 5/10 or greater
  • Had fatigue 5/10 or greater
  • Were not currently treated within one month with surgery, radiotherapy, chemotherapy, steroids, nonsteroidal anti-inflammatory drugs (NSAIDs), appetite stimulants, or progestational agents
  • Had no bowel obstruction, ascites, endocrine abnormalities, diabetes mellitus, severe anemia, or bleeding.

Setting:

The study was conducted in a community outpatient setting in Argentina.

Study Design:

The study used a pilot, open-label, uncontrolled convenience sample design.

Measurement Instruments/Methods:

Weekly measurements included

  • Performance status
  • Appetite
  • Nausea
  • Fatigue Numerical Scale (FNS, 0-10)
  • Calculations of lean mass (LM), fat mass (FM), total body water (TBW), caloric intake, mid-arm circumference (MAC), caregiver’s report of volume of supplement consumed, blood chemistry, C-reactive protein (CRP), interleukin-10 (IL-10), and granulocyte-macrophage colony-stimulating factor (GM-CSF) levels.

Results:

  • Thirteen of eighteen participants showed stable or increased weight compared with prestudy (p = 0.0001).
  • Of the patients, 100% had a lowered rate of weight loss.
  • Less than 20% of patients followed advice to exercise.
  • Significant differences were noted in nausea, fatigue, appetite, performance status, and MAC.
  • Some improvement trends were observed in body weight index (BWI) (body mass) and LM.
  • No significant differences were noted in FM and TBW.

Limitations:

  • The study was uncontrolled.
  • The study had a small sample size.
  • FNS was the only tool used to measure fatigue.
  • Cox-2 inhibitor may prevent reduction of IL-10, causing more infectious complications.

Nursing Implications:

Cost of medications, polymeric diet, and cost of cytokine measurements should be considered.

Jensen, M. B., & Hessov, I. (1997). Randomization to nutritional intervention at home did not improve postoperative function, fatigue or well-being. British Journal of Surgery, 84, 113–118.

doi: 10.1002/bjs.1800840141
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Study Purpose:

Postoperative fatigue and deterioration in functional capacity have been correlated with postoperative weight loss. Nutritional support to enhance the regain of weight may be beneficial to convalescence.

Intervention Characteristics/Basic Study Process:

Patients received soy protein supplements and dietician home visits and traveled five times during the 180 days in the postoperative period after discharge.

Sample Characteristics:

The study included 32 patients undergoing elective colorectal surgery; 22 (69%) had cancer.

Setting:

The study was conducted in a community setting in Denmark.

Phase of Care and Clinical Applications:

Patients were undergoing the active treatment, postoperative phase of care.

Study Design:

This was a randomized trial with a usual care comparison group; patients and investigators were not blinded to treatment assignment.

Measurement Instruments/Methods:

  • Ordinal fatigue scale (1–10) 
  • General Well-Being (GWB)
  • Quality of Life Index (QLI)
  • Quality of life visual analog scale (VAS)
  • Lambert Disability Screening Q (body care, mobility, sensory, social)
  • Functional measures of hand grip
  • Forced Expiratory Volume (FEV1)

Results:

The intervention group consumed significantly more protein than the control group. The intervention group slowly gained weight (p = 0.005) and body mass (p = 0.002) compared to the control group. Both groups had comparable scores for fatigue, functional status, and disability at discharge, 160 days, and the conclusion of the evaluation period.

Limitations:

  • The study had a small sample size.
  • Outcome assessors were not blinded to treatment condition.

Mantovani, G., Macciò, A., Madeddu, C., Gramignano, G., Lusso, M. R., Serpe, R., . . . Deiana, L. (2006). A phase II study with antioxidants, both in the diet and supplemented, pharmaconutritional support, progestagen, and anti-cyclooxygenase-2 showing efficacy and safety in patients with cancer-related anorexia/cachexia and oxidative stress. Cancer Epidemiology, Biomarkers and Prevention, 15, 1030–1034.

doi: 10.1158/1055-9965.EPI-05-0538
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Intervention Characteristics/Basic Study Process:

The integrated treatment consisted of the following components:

  1. High polyphenols content (400 mg)
  2. Antioxidant treatment (300 mg/d a-lipoic acid + 2.7 g/d carbocisteine lysine salt + 400 mg/d vitamin E + 30,000 IU/d vitamin A + 500 mg/d vitamin C)
  3. Pharmaconutritional support enriched with 2 cans per day (n-3) ​polyunsaturated fatty acids (PUFA) (eicosapentaenoic acid and docosahexaenoic acid), 500 mg/d medroxyprogesterone acetate, and 200 mg/d selective cyclooxygenase-2-inhibitor celecoxib.

Patient outcomes were assessed at baseline and one, two, and four months.

Sample Characteristics:

  • The sample included 39 patients with cancer-related anorexia/cachexia syndrome (CACS).
  • Mean age was 58.9 years (range 42–78).
  • The majority of patients were male (n = 23).
  • Patients had multiple tumor sites, but the most common was head and neck (43.6%); 97.4% were stage IV.

Setting:

Not identified

Phase of Care and Clinical Applications:

Patients were undergoing the active treatment phase of care.

Study Design:

This was an open, early-phase II study.

Measurement Instruments/Methods:

Multidimensional Fatigue Symptom Inventory–Short Form (MFSI-SF)

Results:

Compared to baseline scores, fatigue outcomes improved at two months (p = 0.22) and more so at four months (p = 0.004). No correlation existed between changes in fatigue and changes in any other variable studied.

Limitations:

  • The study lacked a neutral comparison group.
  • The study had a small sample size.

Mantovani, G., Macciò, A., Madeddu, C., Gramignano, G., Serpe, R., Massa, E., . . . Floris, C. (2008). Randomized phase III clinical trial of five different arms of treatment for patients with cancer cachexia: interim results. Nutrition, 24, 305–313.

doi: 10.1016/j.nut.2007.12.010
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Intervention Characteristics/Basic Study Process:

All patients received basic treatment with polyphenols (300 mg/day) from alimentary sources (e.g., onions, apples, oranges, red wine, and green tea) or supplementary tablets. Patients also received antioxidant agents (a-lipoic acid and carbocisteine), as well as vitamins A, C, and E, orally. All patients then were randomized to one of the following five treatment arm interventions:

  1. Progestational agent medroxyprogesterone acetate (MPA) 500 mg/day or megestrol acetate (MA) 320 mg/day
  2. Oral supplementation of eicosapentaenoic acid (EPA)-enriched nutritional supplements, with docosahexaenoic acid, high-calorie, and high-protein content
  3. L-carnitine 4 g/day, orally
  4. Thalidomide 200 mg/day, orally
  5. MPA or MA plus pharmacologic nutritional support, L-carnitine, and thalidomide.

The planned treatment duration was four months. Patient outcomes were evaluated at 4, 8, 16, and 24 weeks.

Sample Characteristics:

  • The sample was comprised of 125 adult patients with cancer and cancer cachexia (mean age = 69.1 years [range 35–80]).
  • The male/female ratio was 74/51.
  • A majority (83%) of patients experienced more than 5% weight loss before study entry and were stage IV (94.4%).
  • Patients had varied diagnoses, the most common being lung (14.4%) and breast (14.4%) cancer.
  • Patients were excluded if they were women of child-bearing age, had significant comorbidities, had a mechanical obstruction to feeding, underwent medical treatments that induced significant changes to body metabolism or weight, or had contradiction to MPA or MA.

Setting:

Policlinico Universitario and Ospedale Oncologico Regionale, Cagliari, Italy

Study Design:

The study was a randomized, phase II, two-center clinical trial with five treatment arms.

Measurement Instruments/Methods:

Multidimensional Fatigue Symptom Inventory–Short Form (MFSI-SF)

Results:

When comparing baseline and posttreatment measures, statistically significant improvements in fatigue outcomes were observed in the L-carnitine treatment arm (p = 0.039) and the MPA/MA plus pharmacologic nutritional support, L-carnitine, and thalidomide arm (p = 0.015). Fatigue worsened significantly in patients receiving EPA-enriched oral supplementation treatment (p = 0.051).

Limitations:

  • No placebo arm was included because an approved drug for cancer cachexia treatment was available at the time of study (MPA or MA).
  • The results were from an interim report.

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