Table 1.
Clinical Studies Investigating the Effects of Diet in Heart Failure
| Study | Trial Type | EF (%) | N | Dietary Intervention | Outcomes |
|---|---|---|---|---|---|
| Sodium Restriction | |||||
| Online Reference (1) | Randomized controlled trial | 40±15.6 (Intervention) 42.3±15.5 (Control) |
65 | 2,000–2,400 mg/day sodium vs. control for 6 months | Increase in physical activity and QoL assessed by a sum of KCCQ and MLHFQ scores and improvement in NYHA class in intervention group vs. control. |
| Online Reference (2) | Randomized trial | EF <35% | 232 | 2,760 mg/day vs. 1,840 mg/day sodium in recently decompensated patients (30 days post-discharge) | 2,760 mg/day sodium group had lower readmissions at 180 days (primary endpoint) and combined readmission and mortality at 90 days. |
| Online Reference (3) | Randomized single-blind controlled trial | 26.0±8.7 | 75 | Inpatient, admitted for decompensated HF 800 mg/day sodium restriction vs. control until 7th day of hospitalization or discharge |
No differences in 3-day change in weight and clinical congestion score in intervention vs. control (primary endpoint) and 30-day readmissions in intervention vs. control. |
| Online Reference (4) | Multicenter, randomized controlled trial | 34±11 (Intervention) 37±15 (Control) |
97 | 2,000–3,000 mg/day sodium restriction vs. control for 12 weeks | The intervention group demonstrated signs of clinical improvement vs. control (composite primary outcome), driven mostly by improvement in NYHA class and edema. |
| Online Reference (5) | Open-label, randomized controlled pilot trial | 42.0 (25.0–50.5) | 38 | 1,500 mg/day (low) vs. 2,300 mg/day (moderate, control) sodium restriction for 6 months | BNP decreased from baseline in the low sodium group alone but there were no significant differences between groups; KCCQ clinical score increased in both groups with no difference between groups. |
| Dietary Patterns | |||||
| Online Reference (6) | Open-label pilot trial | 69±6 | 13 | 21 days of home delivered DASH/sodium restricted diet (1,150 mg sodium/day) | DASH diet lowered clinic and 24-hour ambulatory blood pressure and BNP. Cardiac systolic and diastolic function, 6MWT and NYHA class were improved. |
| Online Reference (7) | Randomized controlled trial | 41±13 (DASH) 40±15 (Control) |
48 | 3 months of DASH diet intervention vs. control | Endothelial function was not better in the DASH group (primary endpoint) but quality of life assessed by MLHFQ and 6MWT was improved vs.control. |
| Online Reference (8) | Multicenter, randomized single-blind controlled trial |
39±18 | 66 | Home delivered DASH/sodium restricted diet (1,500 mg sodium/day) vs. control for 30 days post-hospital discharge for HF exacerbation | No significant difference between groups in change of KCCQ summary score (primary endpoint). There was a trend towards lower HF rehospitalization at 30 days in DASH vs. control. |
| Online Reference (9) | Multicenter, prospective, observational study | 51±14 | 991 | Adherence to a Mediterranean diet assessed by patient questionnaire in those seen in the emergency department for acute HF | After a mean follow up of 2.1±1.3 years, adherence to the Mediterranean diet was not associated a decrease in all-cause mortality (primary endpoint) but was associated with a decrease in rehospitalizations for HF. |
| Online Reference (10) | Cross sectional analysis | 39±20 | 372 | Analysis of adherence to Mediterranean dietary pattern via food frequency questionnaire and MedDietScore | A Mediterranean dietary pattern was associated with improvements in filling pressure (via log E/A ratio). |
| Online Reference (11) | Multicenter, prospective cohort study | 21.5 (15.3–28.9) | 318 | Analysis of diet via food frequency questionnaire in candidates waitlisted for a heart transplant | After median follow-up of approximately a year, High sodium diets (correlated with higher fluid and saturated fat intake) were associated with high urgency of transplantation; intake of poly- and monounsaturated fatty acid was associated with a decreased risk of deterioration/mortality. |
| Online Reference (12) | Prospective cohort study | 33.9 ± 14.0 | 212 | Analysis of average lycopene (a carotenoid found in red, orange and yellow produce) intake via four days of food diaries | Greater intake of lycopene was associated with improvements in cardiac event-free survival (related cardiac death and time to first hospitalization for HF), independent of intake of sodium. |
| Fatty Acids | |||||
| Online Reference (13) | Multicenter randomized, double-blind controlled trial | 33.0±8.5 (N-3 PUFA) 33.2±8.5 (placebo) |
6975 | N3 PUFA 1g daily vs. placebo | After a median follow-up of 3.9 years, the N3 PUFA group demonstrated lower all-cause mortality, as well as the combined endpoint of lower all-cause mortality and hospital readmission (primary endpoint). |
| Online Reference (14) | Randomized, double-blind controlled trial | 36±7 (N-3 PUFA) 37±6 (placebo) |
133 | N3 PUFA 1g daily vs. placebo for 12 months | Increase in EF in N3 PUFA vs. placebo (primary endpoint), as well as improvement in diastolic function, decrease in inflammatory biomarkers and lower rate of HF admission. |
| Online Reference (15) | Randomized double-blind controlled trial | 28±1 | 31 | Supplementation of L-alanyl-L-glutamine (8 g/day) and N3 PUFA (6.5 g/day) vs. placebo for 3 months | No change in peak VO2, 6MWT, handgrip or leg/arm skeletal muscle function in intervention vs. placebo (primary endpoints). |
| Online Reference (16) | Cross sectional analysis | 45 (30–60) | 118 | Analysis of averaged 3-day baseline dietary fatty acid consumption for patients enrolled in a sodium restriction trial | As a percent of total kcals, increased PUFA and saturated fatty acids were associated with decreased and increased all-cause mortality, respectively. |
| Online Reference(17) | Cross sectional analysis | 60.4 (57.1–63.0) | 23 | Analysis of baseline 24-hour dietary recall in patients enrolled in a trial for anti-inflammatory therapy | Dietary UFA were positively associated with peak VO2, greater fat-free mass and more favorable diastolic function. |
| Online Reference (18) | Single-arm pilot trial | 58±4 | 9 | In patients with comorbid obesity, 12 weeks of daily supplementation with 1 serving of food rich in UFA. Preferred recommendations for intake were extra-virgin olive oil (54 g), canola oil (54 g), lightly salted mixed tree nuts (walnuts, hazelnuts, almonds and pecans) or peanuts (28 g) | There was an increase in dietary UFA and plasma UFA (primary endpoints). An increase in exercise time and oxygen pulse, as well as a trend towards an increase in peak VO2 was observed. |
| Online Reference (19) | Prospective cohort study | 32±14 | 42 | Analysis of average fatty acid consumption via food diaries from four days | Saturated and trans fat intakes were associated with higher levels of TNF-alpha; omega-3 and PUFA intake were associated with lower sTNF-R1 and sTNF-R2 levels. Both sTNF-R1 and TNF-alpha were associated with decreased event-free survival (emergency department visit or hospitalizations for HF, as well as cardiac mortality). |
| Caloric Restriction | |||||
| Online Reference (20) | Randomized controlled trial | 26±7.3 | 14 | 12 weeks of a calorically restricted diet (500 to 800 kcal deficit), one group with high-protein (30% kcals), another group with standard protein (15% kcals) and a control diet without dietary changes |
Greater weight loss, reduction in waist circumference, fat mass and increase in 6MWT and peak VO2 in the high-protein group vs. the other two groups |
| Online Reference (21) | Randomized controlled trial | 61±6 | 100 | 20 weeks of a 2x2 factorial study to assess the effects of exercise vs. diet 4 groups – exercise (supervised aerobic exercise 3x week), caloric restriction alone (400 kcal deficit), exercise and caloric restriction combined and control |
The independent effects of diet from baseline included increased peak VO2, but no effect on MLHF total score (primary endpoints). Exercise time, peak workload, 6MWT, reduction in weight, fat mass, inflammatory biomarkers and total KCCQ score also improved with diet. |
| Protein and Amino Acid Supplementation | |||||
| Online Reference (22) | Randomized double-blind controlled study | 34±9 (Intervention) 32±6 (placebo) |
95 | 30 days of mixed amino acid supplementation (4 g BID) vs. placebo | Peak VO2, workload and oxygen pulse improved in the intervention group but not placebo. |
| Online Reference (23) | Randomized, double-blind controlled pilot trial | 25±10 (Intervention) 24±5 (placebo) |
29 | In patients with clinically significant weight loss, 6 weeks of a high calorie (600 kcal) high protein (20 g) oral nutrition supplement vs. placebo (12 kcal/day) | From baseline, intervention increased weight gain and overall MLHFQ score (primary endpoints), as well as 6MWT. Peak VO2 was not increased. |
| Online Reference (24) | Randomized controlled trial | Not described | 66 | 3 months of resistance training plus branch-chain amino acid supplement (10 g/day) vs. resistance training alone | There were no effects of branch chain amino acids on muscle strength or peak VO2 |
| Online Reference (25) | Open-label, randomized controlled trial | 32.4±6.3 (Intervention) 32.4±7.3 (Control) |
50 | 500 mg orodispersible L-carnosine vs. control for 6 months | In intervention vs. control, there was an increase in 6MWT, peak VO2, workload, and quality of life by visual analog score. |
| Oral Micronutrient Supplementation | |||||
| Online Reference (26) | Randomized, double-blind controlled trial | 26.1±6.7 | 32 | Daily multiple micronutrient supplement vs. placebo for 9 months | Increase in LVEF in the micronutrient group vs. placebo (primary endpoint), as well an increase in quality of life scores assessed by questionnaire. 6MWT, NYHA class and inflammatory biomarkers remained unchanged in both groups. |
| Online Reference (27) | Randomized, double-blind, controlled trial | 38.3±11.4 (Intervention) 45.1±9.0 (Control) |
74 | Daily multiple micronutrient supplement vs. placebo for 12 months | No significant difference in EF between intervention and placebo (primary endpoint) or in MLHFQ questionnaire score, 6MWT, NTproBNP and inflammatory biomarkers. |
| Online Reference (28) | Randomized, double blind control crossover trial | 29.5±2.5 | 9 | 28 days of treatments with 300 mg/day thiamine vs. placebo | Significant improvement in EF in thiamine group vs. placebo (primary endpoint); trend towards improvement in 6MWT. |
| Online Reference (29) | Multicenter, randomized double-blind controlled trial | 31±10 | 420 | 2 years of treatment with CoQ10 100 mg 3x daily vs. placebo | Reduction in major adverse cardiac events in intervention vs. placebo (primary endpoint), as well as a reduction in rates of hospital stays for HF and in all-cause and cardiovascular mortality. |
| Online Reference (30) | Randomized, double-blind randomized crossover trial | 32±2 | 13 | 9 days of 70 ml beet root juice BID that was concentrated vs. depleted in nitrates | No significant difference in time to exercise intolerance between nitrate and placebo (primary endpoint) or peak VO2. |
| Online Reference (31) | Randomized, double-blind, controlled trial | Included only ≥50% | 20 | 1 week of nitrate concentrated vs. depleted beetroot juice | Increase in time to exhaustion during submaximal exercise at in intervention group (primary endpoint), but not after a single acute dose. |
| Online Reference (32) | Randomized, double-blind controlled crossover trial | 34±2 | 8 | Patients ingested 140 ml of a beetroot juice that was nitrate concentrated (intervention) vs. depleted (control) and performed exercise testing 2 hours after | There were no changes in ventilatory responses, but peak VO2 improved after intervention vs. placebo (primary endpoints). |
| Online Reference (33) | Randomized double-blind controlled trial | 37.6±13.9 | 64 | 6 months of weekly 50,000 IU Vitamin D3 vs. placebo | There was no difference in changes in peak VO2 in the intervention group vs. control (primary endpoint) nor in 6MWT. |
| Online Reference (34) | Randomized double-blind controlled trial | 26.1±10.68 | 229 | 100 ug daily Vitamin D3 vs. placebo for 1 year | Vitamin D3 did not increase 6MWD vs. placebo (primary outcome), but did increase EF and improve remodeling. |
| Online Reference (35) | Randomized, double-blind controlled trial | 28 (23–34) (Intervention) 26 (24–35) (placebo) |
892 | 4,000 IU Vitamin D3 daily vs. placebo for 3 years | Vitamin D3 did not reduce all-cause mortality vs. placebo (primary endpoints); there was an increased implantation of mechanical circulatory support in the Vitamin D3 group. |
| Online Reference (36) | Open-label randomized controlled trial | 35±8 | 101 | 6 weeks of 2,000 IU vitamin D3 daily vs. control | Vitamin D3 decreased plasma renin activity (primary endpoint) and decreased plasma renin, but did not change NTproBNP. |
6MWT, 6 Minute Walk Test; BID, twice a day; BNP, brain natriuretic peptide; DASH, Dietary Approaches to Stop Hypertension; EF, ejection fraction; HF, heart failure; KCCQ, Kansas City Cardiomyopathy Questionnaire; kcals, kilocalories; MedDiet Score, Mediterranean Diet Score; MLHFQ, Minnesota Living with Heart Failure Questionnaire; N, number of participant; N-3 PUFA, N-3 Polyunsaturated Fatty Acids; Na, sodium; NYHA, New York Heart Association; peak VO2, peak oxygen consumption; QoL, quality of life; UFA, Unsaturated Fatty Acids