Skip main navigation

Nutrient Deficiencies in Heart Failure: A Micro Problem With Macro Effects?

Originally published of the American Heart Association. 2018;7:e010447


    Dietary micronutrient deficiency is common in adults with heart failure (HF), with >20% having low intake of vitamin A, calcium, magnesium, selenium, and iodine and up to 75% having low intake of vitamin D.1 Micronutrients are necessary cofactors for normal cardiac metabolism, and deficiencies have been implicated in the development and progression of HF.2 There is increasing interest in nutrition among patients with HF, two thirds of whom report taking vitamins or supplements, despite limited evidence of impact on outcomes.4 Acknowledging this disconnect, the National Heart, Lung, and Blood Institute and the National Institutes of Health Office of Dietary Supplements convened a Working Group in 2013 to address the impact of nutrition on HF, which recognized substantial knowledge gaps and a need to improve the quality of evidence.6

    In this issue of the Journal of the American Heart Association (JAHA), Lennie and colleagues present a multicenter prospective cohort study evaluating the impact of dietary micronutrient deficiencies on clinical outcomes in ambulatory patients with HF.7 The study enrolled 274 patients recruited from 3 HF clinics affiliated with academic medical centers in Georgia, Indiana, and Kentucky, with 1‐year follow‐up. Patients were eligible if they had documented HF with either reduced or preserved ejection fraction with clinical stability for 3 months. Primary exclusion criteria included urgent listing for cardiac transplantation or presence of a left ventricular assist device, end‐stage illness that would considerably shorten life expectancy, or conditions other than HF or diabetes mellitus that required dietary restrictions. Four‐day food diaries were collected from 246 patients to estimate the intake of 17 micronutrients, including 11 vitamins and 6 minerals. Deficiencies were defined by the Institute of Medicine's Food and Nutrition Board recommendations,8 and a summary score was created. Dichotomized micronutrient deficiency was the key independent variable in the analysis, with patients deficient in ≥7 micronutrients considered to have high micronutrient deficiency. The primary outcome of the study was survival free of all‐cause hospitalization or death.

    The median (range) number of deficiencies was 4 (0–14) micronutrients. Patients with high micronutrient deficiency were more likely to be younger, to be nonwhite, and to have more depressive symptoms measured using the Beck Depression Inventory II. Notably (for a study focused on malnutrition), the mean baseline body mass index was >30 kg/m2 and was similar between the groups. Additional important characteristics of the diet differed between groups, including lower energy and sodium intake, albeit with higher sodium per 1000 kcal in the high micronutrient deficiency group. The primary outcome of all‐cause hospitalization or death occurred in 44% (n=27) of the high micronutrient deficiency group versus 25% (n=47) of the low‐deficiency group, driven primarily by hospitalizations. In the time‐to‐event analysis adjusting for race, comorbidity, body mass index, depression, estimated sodium intake, and HF severity, patients with high micronutrient deficiency had almost double the hazard of events compared with those without (hazard ratio [95% confidence interval], 1.92 [1.15–3.21]). This association remained after both the addition of NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) to the model and in a sensitivity analysis adjusting for caloric intake. These findings in US patients with HF support and extend similar observations by these authors in a South Korean cohort.9

    This study was well designed, with several key strengths. Self‐reported dietary assessment methods are challenging to do well and are without an established gold standard for comparison. In this study, meticulous food diaries, including both weekends and weekdays, were collected by participants with rigorous in‐person verification. Although challenging to replicate in larger studies, such “documented” food diaries are clearly superior to unverified food records.10 Appropriate methods for determining micronutrient deficiency were used, including probability ratios when population‐based data were available and reference standards when these were not. Attempts were made to adjust for other potential dietary mediators, such as sodium and energy intake. Finally, many patients were enrolled from multiple sites with detailed follow‐up of clinical events, limiting potential bias.

    However, important questions and opportunities remain. Participants were surveyed after 3 months on stable medical therapy without hospitalization. This strategy presumably reduces variability in dietary intake related to acute illness but excludes the patients most at risk. Depending on illness severity and the screening method, 15% to 90% of patients hospitalized for HF are undernourished. Malnutrition markedly increases the risk for hospital readmission and death.11 Yet, little is known about how dietary intake changes over the course of HF or how such changes may affect outcomes. Ideally, future studies on this topic would repeat dietary assessments around the time of HF hospitalization and assess the overall burden of recurrent hospitalizations, institutionalization, and death.

    Two other clinically relevant points are important to emphasize. First, diuretics, nearly ubiquitous in HF management, increase excretion of and contribute to deficiencies in water‐soluble vitamins, such as thiamine.12 Although the analysis adjusted for HF severity using the Seattle Heart Failure Model score, which includes diuretic prescription and dosing,13 the dietary model likely underestimated the true severity of some micronutrient deficiencies in HF. Second, low body weight is an ominous prognostic sign in HF and is generally assumed to reflect cardiac cachexia, malnutrition, or both. It is striking that among patients with high micronutrient deficiency in the current study, 49% were obese and none were underweight. In a recent large cohort study, severe malnutrition appeared uncommon in obese patients with HF. However, the screening instruments used were based on body mass index and blood biomarkers, which also reflect inflammation.14 As the authors suggest, a high index of suspicion and a more nuanced assessment are needed to characterize malnutrition in obese patients with HF, particularly in those with acute decompensation.

    Current HF guidelines recognize that although nutrition is likely important, more data are needed to provide adequate dietary guidance.15 Work centered on single micronutrient deficiency and supplementation in HF has produced mostly neutral results in clinical trials.3 This fact, along with increasing controversy related to dietary sodium restriction,16 has led to growing interest in overall dietary quality. In the Women's Health Initiative cohort, participants with HF who had greater adherence to the Dietary Approaches to Stop Hypertension eating pattern had slightly lower mortality over a median of 4 years, with a similar trend for Mediterranean diet adherence.17 However, even the best observational studies can be limited by the logistical challenges and accuracy of nutrient measurement, and resulting associations between diet and outcomes can be affected by unmeasured confounders.18

    A few small clinical trials have moved beyond dietary risk assessment in cohort studies and the supplementation of single micronutrients to directly assess the effects of nutritional support in HF. The PICNIC (Nutritional Intervention Program in Hospitalized Patients With Heart Failure Who Are Malnourished) study randomized 120 Spanish inpatients with HF at risk for nutritional complications to a multidisciplinary dietary intervention. The program involved tailored dietary recommendations delivered through monthly in‐person nutrition‐focused visits. With this intensive support, 27% of patients died or were hospitalized for HF over 12 months of follow‐up, versus 61% in the usual care group.19 The recently published GOURMET‐HF (Geriatric Out‐of‐Hospital Randomized Meal Trial in Heart Failure) pilot study randomized 66 US patients with HF at hospital discharge to 4 weeks of home‐delivered, low‐sodium, Dietary Approaches to Stop Hypertension–compliant meals compared with usual care. Although the primary outcome of disease‐specific quality of life did not differ between groups, secondary analyses showed a trend toward reduction in HF symptoms and 30‐day readmissions in the group receiving meals.20

    The study by Lennie and colleagues7 provides another important link between micronutrient deficiencies and outcomes in patients with HF. The findings promote much‐needed thinking beyond sodium restriction or individual nutrient supplementation toward maintaining overall dietary quality. The time is right to conduct larger clinical trials of comprehensive dietary support in HF, which hold strong potential to improve quality of life and outcomes in this vulnerable population.

    Sources of Funding

    Dr. Hummel is supported by the Agency for Healthcare Research and Quality Veterans Health Administration R21‐HS024567 and I01‐CX001636 (Hummel).


    Hummel has previously received funding to conduct dietary intervention studies in heart failure from PurFoods, LLC. Cascino has no disclosures to report.


    *Correspondence to: Scott L. Hummel, MD, MS, 1500 E Medical Center Dr, SPC 5853, Ann Arbor, MI 48109‐5853. E‐mail:


    • 1 McKeag NA, McKinley MC, Harbinson MT, McGinty A, Neville CE, Woodside JV, McKeown PP. Dietary micronutrient intake and micronutrient status in patients with chronic stable heart failure: an observational study. J Cardiovasc Nurs. 2017; 32:148–155.CrossrefMedlineGoogle Scholar
    • 2 Witte KK, Clark AL, Cleland JG. Chronic heart failure and micronutrients. J Am Coll Cardiol. 2001; 37:1765–1774.CrossrefMedlineGoogle Scholar
    • 3 Soukoulis V, Dihu JB, Sole M, Anker SD, Cleland J, Fonarow GC, Metra M, Pasini E, Strzelczyk T, Taegtmeyer H, Gheorghiade M. Micronutrient deficiencies an unmet need in heart failure. J Am Coll Cardiol. 2009; 54:1660–1673.CrossrefMedlineGoogle Scholar
    • 4 McKeag NA, McKinley MC, Woodside JV, Harbinson MT, McKeown PP. The role of micronutrients in heart failure. J Acad Nutr Diet. 2012; 112:870–886.CrossrefMedlineGoogle Scholar
    • 5 Witte KK, Byrom R. Micronutrients for chronic heart failure: end of the road or path to enlightenment?JACC Heart Fail. 2014; 2:318–320.CrossrefMedlineGoogle Scholar
    • 6 Nutrition and Diet in Heart Failure Management. National Heart, Lung, and Blood Institute (NHLBI) 2013. Accessed August 1, 2018.Google Scholar
    • 7 Lennie TA, Andreae C, Rayens MK, Song EK, Dunbar SB, Pressler SJ, Heo S, Kim J, Moser DK. Micronutrient deficiency independently predicts time to event in patients with heart failure. J Am Heart Assoc. 2018; 7:e007251. DOI: 10.1161/JAHA.117.007251.LinkGoogle Scholar
    • 8 Institute of Medicine Subcommittee on Interpretation, Uses of Dietary Reference Intakes, Institute of Medicine Standing Committee on the Scientific Evaluation of Dietary Reference Intakes . DRI Dietary Reference Intakes: Applications in Dietary Assessment. Washington, DC: National Academies Press (US); 2000. Accessed August 1, 2018.Google Scholar
    • 9 Song EK, Moser DK, Kang SM, Lennie TA. Association of depressive symptoms and micronutrient deficiency with cardiac event‐free survival in patients with heart failure. J Card Fail. 2015; 21:945–951.CrossrefMedlineGoogle Scholar
    • 10 Kwan ML, Kushi LH, Song J, Timperi AW, Boynton AM, Johnson KM, Standley J, Kristal AR. A practical method for collecting food record data in a prospective cohort study of breast cancer survivors. Am J Epidemiol. 2010; 172:1315–1323.CrossrefMedlineGoogle Scholar
    • 11 Lin H, Zhang H, Lin Z, Li X, Kong X, Sun G. Review of nutritional screening and assessment tools and clinical outcomes in heart failure. Heart Fail Rev. 2016; 21:549–565.CrossrefMedlineGoogle Scholar
    • 12 Seligmann H, Halkin H, Rauchfleisch S, Kaufmann N, Motro M, Vered Z, Ezra D. Thiamine deficiency in patients with congestive heart failure receiving long‐term furosemide therapy: a pilot study. Am J Med. 1991; 91:151–155.CrossrefMedlineGoogle Scholar
    • 13 Levy WC, Mozaffarian D, Linker DT, Sutradhar SC, Anker SD, Cropp AB, Anand I, Maggioni A, Burton P, Sullivan MD, Pitt B, Poole‐Wilson PA, Mann DL, Packer M. The Seattle Heart Failure Model: prediction of survival in heart failure. Circulation. 2006; 113:1424–1433.LinkGoogle Scholar
    • 14 Sze S, Pellicori P, Kazmi S, Rigby A, Cleland JGF, Wong K, Clark AL. Prevalence and prognostic significance of malnutrition using 3 scoring systems among outpatients with heart failure: a comparison with body mass index.. JACC Heart Fail. 2018; 6:476–486.CrossrefMedlineGoogle Scholar
    • 15 Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013; 128:e240–e327.LinkGoogle Scholar
    • 16 Hummel SL, Konerman MC. Dietary sodium restriction in heart failure: a recommendation worth its salt?JACC Heart Fail. 2016; 4:36–38.CrossrefMedlineGoogle Scholar
    • 17 Levitan EB, Lewis CE, Tinker LF, Eaton CB, Ahmed A, Manson JE, Snetselaar LG, Martin LW, Trevisan M, Howard BV, Shikany JM. Mediterranean and DASH diet scores and mortality in women with heart failure: the Women's Health Initiative. Circ Heart Fail. 2013; 6:1116–1123.LinkGoogle Scholar
    • 18 Cobb LK, Anderson CAM, Elliott P, Hu FB, Liu K, Neaton JD, Whelton PK, Woodward M, Appel LJ; American Heart Association Council on Lifestyle and Metabolic Health. Methodological issues in cohort studies that relate sodium intake to cardiovascular disease outcomes: a science advisory from the American Heart Association. Circulation. 2014; 129:1173–1186.LinkGoogle Scholar
    • 19 Bonilla‐Palomas JL, Gámez‐López AL, Castillo‐Domínguez JC, Moreno‐Conde M, López Ibáñez MC, Alhambra Expósito R, Ramiro Ortega E, Anguita‐Sánchez MP, Villar‐Ráez A. Nutritional intervention in malnourished hospitalized patients with heart failure. Arch Med Res. 2016; 47:535–540.CrossrefMedlineGoogle Scholar
    • 20 Hummel SL, Karmally W, Gilespie BG, Helmke S, Teruya S, Wells JM, Trumble E, Jimenez OJ, Marolt C, Wessler JD, Cornellier ML, Maurer MS. Home‐delivered meals postdischarge from heart failure hospitalization: the GOURMET‐HF pilot study. Circ Heart Fail. 2018; 11:e004886.LinkGoogle Scholar


    eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.

    Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.