1. Top of page
  2. Abstract
  3. Micronutrients
  4. Omega-3 Fatty Acids
  5. Vitamin D
  6. Future of Nutrition in HF
  7. References

Congest Heart Fail. 2011;17:199–203. © 2011 Wiley Periodicals, Inc.

Heart failure (HF) is a growing epidemic worldwide with a particularly large presence in the United States. Nutritional assessment and supplementation is an area that can be studied to potentially improve the outcomes of these chronically ill patients. There have been many studies reporting the effect of various nutrients on HF patients, often with mixed results. Amino acids such as taurine, which is involved in calcium exchange, has been reported to improve heart function. Coenzyme Q10, a key component in the electron transport chain, is vital for energy production. l-carnitine, an amino acid derivative, is responsible for transport of fatty acids into the mitochondria along with modulating glucose metabolism. Thiamine and the other B vitamins, which serve as vital cofactors, can often be deficient in HF patients. Omega-3 fatty acid supplementation has been demonstrated to benefit HF patients potentially through anti-arrhythmic and anti-inflammatory mechanisms. Vitamin D supplementation can potentially benefit HF patients by way of modulating the renin-angiotensin system, smooth muscle proliferation, inflammation, and calcium homeostasis. Although supplementation of all of the above nutrients has the potential to benefit patients with HF, more studies are needed to solidify these recommendations. Congest Heart Fail.

Heart failure (HF) is a growing epidemic worldwide with a particularly large presence in the United States. There are approximately 5 million persons in the United States who have HF, with more than 550,000 new patients diagnosed each year.1,2 In 2010, $39.2 billion was spent in the United States for the management of HF.1 Because of the high prevalence and incidence of HF, much research has been devoted to the care of these patients. This research has led to the current guidelines for HF therapy, which include β-blockers, angiotensin receptor blockers, aldosterone antagonists, diuretics, cardiac resynchronization, and implantable cardiac-defibrillators.2 Although these therapies have been shown to decrease morbidity and mortality and even improve quality of life, additional management strategies need to be studied to further improve the outcomes of these chronically ill individuals. One area of HF management that has limited study and application is nutritional assessment and supplementation. This review will describe the different nutrients that are potentially important for the HF patient and provide some of the supporting evidence (Table).

Table Table.   Nutrients Important in Heart Failure Patients
Amino acids: taurine
Coenzyme Q10
Thiamine (vitamin B1)
Riboflavin (vitamin B2)
Pyridoxine (vitamin B6)
Omega-3 fatty acids
Vitamin D
Magnesium, potassium, zinc, selenium


  1. Top of page
  2. Abstract
  3. Micronutrients
  4. Omega-3 Fatty Acids
  5. Vitamin D
  6. Future of Nutrition in HF
  7. References

There are extreme metabolic demands on the adult human heart, which is responsible for pumping approximately 5 L of blood per minute at rest and up to 24 L/min during vigorous exercise. The heart will circulate more >7200 L/d and >2.6 million L/y. During the course of 80 years, the average heart will pump more than 3 billion times. The predominant energy source is fatty acids, but the heart can also easily utilize carbohydrates or both carbohydrates and fatty acids simultaneously. Both of these energy sources are converted into adenosine triphosphate (ATP), which is hydrolyzed by the heart to continue its pump function. Micronutrients and macronutrients are essential for maintaining this highly efficient machine’s parts for the life of the human it occupies by way of renewing enzymes, membranes, and structural elements with amino acids, lipids, and carbohydrates that are either synthesized or consumed in the diet. Micronutrients of importance include coenzyme Q10 (Co Q10), l-carnitine, thiamine, amino acids such as taurine, omega-3 fatty acids, and vitamins. Many of these micronutrients have been noted to be deficient in patients with HF.3,4

Amino acids are a vital nutrient for cardiac metabolism in that they are the foundation from which proteins are constructed as well as serve as an intermediary metabolite. Of particular importance is taurine, which is not involved in protein synthesis; however, taurine is reported to make up one fourth of the amino acid pool in the heart and functions as an antioxidant and regulates calcium homeostasis.4 Taurine modulates a variety of calcium exchange mechanisms to ensure optimal levels and prevent cellular overloads or deficiencies.5 In a recently published randomized controlled trial of taurine supplementation in HF patients, those who received taurine supplements had better exercise capacity than those who received placebo.6 Taurine supplementation has also been shown to lower left ventricular (LV) end-diastolic pressures6 as well as improve systolic function.8,9 In a study of taurine transporter knock out mice, it was observed that they reverted to a fetal cardiac phenotype and had cardiomyocyte atrophy, mitochondrial and myofiber damage, and ultimately cardiac dysfunction.10

Co Q10, also known as ubiquinone, is an important component of the electron transport chain in the mitochondria and is essential for the production of the heart’s major energy source, ATP. Co Q10 has also been shown to act as an antioxidant that decreases low-density lipoprotein oxidation.11 Unfortunately, in patients with HF, serum and tissue levels of Co Q10 have been shown to be lower.12 In addition to this fact, statins, commonly used by HF patients, are HMG-CoA reductase inhibitors that can further deplete the body of this vital nutrient.13 It has been suggested that the degree of Co Q10 deficiency can correlate to worse LV function and mortality.14,15 For this reason, several studies looked at the supplementation of Co Q10 in HF patients. Significant improvement in ejection fraction,16 stroke volume,16,17 cardiac output,17 pulmonary artery pressure,17 functional capacity,18,19 and quality of life20 has been shown in trials of Co Q10. Although there is a good deal of evidence supporting Co Q10 supplementation, some studies showed no benefit,21,22 leaving us with mixed results. Recently, however, meta-analyses have shown significant benefit of Co Q10 supplementation in HF patients.23 Co Q10 also has been shown in a meta-analysis to lower systolic blood pressure by up to 17 mm Hg and diastolic blood pressure by up to 10 mm Hg, without major adverse side effects in patients with essential hypertension.24

l-carnitine is derived from amino acids and is responsible for the transport of fatty acids into the mitochondria from the cytosol.25 It also has a role in modulating glycolysis, the Krebs cycle, and glucose metabolism. Propionyl-l-carnitine, a derivative of l-carnitine, has also been shown to be involved in the Kreb’s cycle as well as increased glucose oxidation and improved contractile function.26 Although l-carnitine can be produced endogenously as well as provided by diet, low levels have been observed in HF patients.27 In a study by Serati and colleagues,28 treatment with l-carnitine resulted in improved diastolic parameters by echocardiography when compared with those who received placebo. In a randomized, double-blind, placebo-controlled multicenter trial conducted by Iliceto and colleagues,28 supplementation of l-carnitine post–myocardial infarction was shown to attenuate LV dilatation. Rizos demonstrated a mortality benefit in New York Heart Association class II or IV patients treated with l-carnitine.30 Despite the positive results in studies investigating the effect of l-carnitine on HF, there have been others that have shown no benefit.31 In summary, l-carnitine supplementation has been shown to improve exercise capacity, maximum exercise time, peak heart rate, and peak oxygen consumption as well as hemodynamic and echocardiographic parameters in HF patients in a variety of studies.4 However, more studies are needed to truly demonstrate the benefits of l-carnitine supplementation in HF patients.

Thiamine, otherwise known as vitamin B1, serves as a key cofactor in carbohydrate metabolism. It is not synthesized in humans, and little thiamine is stored endogenously. As such, continual ingestion is required to prevent thiamine deficiency.3 The effects of thiamine deficiency and the benefit of thiamine supplementation are disease- and medication-dependent.3 Severe thiamine deficiency can result in severe vasodilatation and high-output HF, known as wet beriberi. This form of thiamine deficiency clearly warrants thiamine supplementation; however, wet beriberi is increasingly uncommon.3 The benefit of thiamine supplementation in less severe forms of thiamine deficiency is still unclear. Thiamine deficiency in HF has typically been attributed to the use of loop diuretics, which promote the excretion of thiamine and other water-soluble B vitamins.32,33 However, poor dietary intake is likely a contributing factor in many patients.34 A series of studies have shown thiamine deficiency to be fairly common in the HF population, with prevalence ranging from 13% to 33%.35,36 The prevalence may be even higher in hospitalized and elderly patients with HF.36,37 A number of small studies have shown improved markers of LV function after thiamine supplementation. Shimon and colleagues38 enrolled 30 patients with thiamine deficiency taking loop diuretics and provided 7 weeks of thiamine supplementation.38 Twenty-seven of the 30 patients showed a mean improvement in LV ejection fraction of 22%. Another study by Seligmann and colleagues32 treated 23 HF patients with a 7-day course of intravenous thiamine and demonstrated a mean improvement in ejection fraction of 13% and a mean increase in systolic blood pressure of 10 mm Hg. Studies have shown that the use of spironolactone helps to abate the excretion of thiamine and improve serum thiamine levels.39,40 Moreover, even small doses of thiamine (1.5 mg/d) appear to prevent thiamine deficiency in HF patients.35 Other studies have shown mixed results from thiamine supplementation in HF.37,41 Larger studies are necessary to examine the benefit of thiamine supplementation in HF, but it appears reasonable to supplement thiamine in chronic HF patients, especially those taking high-dose loop diuretics.

Riboflavin and pyridoxine are water-soluble B vitamins that play a key role in the beta-oxidation of lipids, carbohydrate metabolism, and red blood cell production. Like thiamine, these vitamins show increased excretion with loop diuretics.42 Riboflavin and pyridoxine deficiencies have been demonstrated in chronic HF patients. One study of 100 patients reported riboflavin deficiency in 27% and pyridoxine deficiency in 38%42 ; however, data regarding supplementation and its effect on cardiac function are lacking.

Hyperhomocysteinemia has been established as an independent risk factor for the development of HF even in the absence of myocardial infarction.43,44 Vitamin B12 and folate deficiencies are the most common cause of elevated plasma homocysteine levels in adults.45 Supplementation of these vitamins can effectively reverse elevated plasma homocysteine levels.46 Studies show that levels of B12 and folate correlate poorly with the development of HF, and supplementation with vitamin B12 or folate has not been investigated.47,48

Other potential important micronutrients in the HF patient include magnesium, potassium, zinc, selenium, and creatine. Magnesium and potassium deficiencies have been associated with arrhythmias. Zinc and selenium are antioxidants that have also been reported to be low in HF patients.4 Creatine is a key component of energy metabolism in the heart muscle and has also been reported to be deficient in patients with severe HF.4

Omega-3 Fatty Acids

  1. Top of page
  2. Abstract
  3. Micronutrients
  4. Omega-3 Fatty Acids
  5. Vitamin D
  6. Future of Nutrition in HF
  7. References

Although reasons for the potential benefits of omega-3 polyunsaturated fatty acids (PUFAs) are not completely understood, omega-3 fatty acids appear to confer cardiovascular benefits largely through docosahexaenoic acid– and eicosapentaenoic acid–enrichment of membrane phospholipids.49 The incorporation of omega-3 PUFA into the membranes of target cells and tissues is likely to produce a reduction in electrical excitability, thus decreasing the potential for arrhythmic events.50 Other beneficial physiologic effects include inhibition of thromboxane production, increased production of prostacyclin, increased fibrinolytic activity of plasma, modification of leukotriene and cytokine production to reduce inflammation, reduction in vasospastic response to catecholamines, reduction in blood viscosity, decreased platelet-activating factor and platelet-derived growth factor, and oxygen free-radical generation.51 These cumulative effects ultimately lead to increased arrhythmic thresholds, reduction in arterial blood pressure, improvement in arterial and endothelial function, reduced platelet aggregation, and favorable affects on autonomic tone.52 Fish oils also decrease tumor necrosis factor (TNF) production in HF and improve body weight.

Omega-3 PUFA supplementation may represent a novel therapeutic approach in late-stage HF characterized by cardiac cachexia.53,54 Supplementation with omega-3 PUFAs has also been of potential interest as a therapy for HF. Trials in primary and secondary prevention of coronary heart disease showed that omega-3 fatty acid supplementation results in a relative risk reduction of 10% to 20% in fatal and nonfatal cardiovascular events.55 The Cardiovascular Health Study showed an inverse association in the intake of baked or broiled fish and incidence of congestive HF.56,57 This result was supported by recent data from the Atherosclerosis Risk in Community (ARIC) study, showing an inverse relationship between omega-3 PUFA intake and incident HF in women.58

Further evidence on the benefit of omega-3 PUFA in HF was shown by the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico Heart Failure (GISSI-HF) investigators. Almost 7000 patients with New York Heart Association class II through IV chronic HF were randomized to receive 1 g/d of omega-3 PUFAs or matching placebo.59 Death from any cause was reduced from 29% with placebo to 27% in those treated with omega-3 fatty acids (adjusted hazard ratio, 0.91; 95.5% confidence interval, 0.833–0.998; P=.041). The co-primary outcome of death or admission to hospital for a cardiovascular event was also reduced. Although the improvements in clinical outcomes were modest, the therapy was safe, well tolerated, and additive to those of other therapies that are standard of care in HF.

Animal studies in cardiac remodeling suggest that higher doses of omega-3 PUFA may be useful.60 In a small 18-week study of 14 patients with class II through IV HF, there was marked improvement in inflammatory cytokines, TNF-α and interleukin 1, with 5.1 g/d of eicosapentaenoic acid and docosahexaenoic acid.53 These findings were echoed in the GISSI-HF study. Effect of n-3 PUFAs in patients with chronic HF in the GISSI-HF trial, a randomized, double-blind, placebo-controlled trial,59 and a Japanese epidemiological study61 both suggest that higher pharmacologic doses of omega-3 PUFA are needed to obtain maximal clinical benefits in patients with HF.

Further studies are needed to determine not only the optimal dose of omega-3 PUFA protection in different stages of HF, but also the underlying mechanism of action responsible for these benefits. It is clear that supplementation with omega-3 PUFA provides significant overall benefit with minimal risk. In a recent editorial published in The Lancet, Fonarow62 concludes that “supplementation with omega-3 PUFAs should join the short list of evidence-based life-prolonging therapies for HF.”62

Vitamin D

  1. Top of page
  2. Abstract
  3. Micronutrients
  4. Omega-3 Fatty Acids
  5. Vitamin D
  6. Future of Nutrition in HF
  7. References

Vitamin D deficiency has been reported to be associated with many of the traditional CV risk factors such as diabetes mellitus, hypertension, and dyslipidemia either directly or indirectly.63 Of particular interest for this review is the association of vitamin D deficiency with increased parathyroid hormone levels and subsequent effect on the modulation of the renin-angiotensin system, cardiac contractility, and smooth muscle proliferation leading to LV hypertrophy.64 The greatest source of vitamin D is sunlight exposure and endogenous production in the skin. Vitamin D can also be obtained from dietary sources but to a much lesser degree.63 Vitamin D deficiency has been reported to be a problem in several different populations ranging from the young and healthy to the elderly and is prevalent in HF patients as well. A study published by Schierbeck and colleagues65 indicated that both low vitamin D and elevated PTH were independently associated with mortality in HF patients.

Future of Nutrition in HF

  1. Top of page
  2. Abstract
  3. Micronutrients
  4. Omega-3 Fatty Acids
  5. Vitamin D
  6. Future of Nutrition in HF
  7. References

Nutrition is an extremely important part of managing HF patients, particularly because many of them may be malnourished. With the large energy and nutrient demands of the human heart, it is essential to keep up with consumption to prevent the further fall in heart function in these already disadvantaged patients. There are physiologic reasons to supplement all of the nutrients we have discussed in this review, yet data still do not exist to be able to make solid recommendations. In addition, have many of the studies that have investigated nutrient supplementation simply fulfilled the need of one nutrient to potentially unmask the need for another? As discussed above, some basic treatment modalities of HF patients such as diuretics can, in and of themselves, contribute to some of the nutrient deficiencies. It is time to investigate the benefits of nutrient supplementation by designing a large randomized controlled trial comparing patients with repleted nutrients vs those who receive placebo. The formulation of nutrients in this study should include many if not all of the ones discussed in this review to answer the question of whether there is benefit.


  1. Top of page
  2. Abstract
  3. Micronutrients
  4. Omega-3 Fatty Acids
  5. Vitamin D
  6. Future of Nutrition in HF
  7. References
  • 1
    Lloyd-Jones D, Adams RJ, Brown TM, et al. Heart disease and stroke statistics – 2010 update: a report from the American Heart Association. Circulation. 2010;121:e46e215.
  • 2
    Hunt SA, Abraham WT, Chin MH, et al. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (writing Committee to update the 2001 guidelines for the evaluation and management of heart failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation. 2005;112:e154e235.
  • 3
    Sole MJ, Jeejeebhoy KN. Conditioned nutritional requirements and the pathogenesis and treatment of myocardial failure. Curr Opin Clin Nutr Metab Care. 2000;3:417424.
  • 4
    Soukoulis V, Dihu JB, Sole M, et al. Micronutrient deficiencies: an unmet need in heart failure. J Am Coll Cardiol. 2009;54:16601673.
  • 5
    Schaffer SW, Kramer J, Chovan JP. Regulation of calcium homeostasis in the heart by taurine. Fed Proc. 1980;39:26912694.
  • 6
    Beyranvand MR, Kadkhodai Khalafi M, Roshan VD, et al. Effect of taurine supplementation on exercise capacity of patients with heart failure. J Cardiol. 2011;57:333337.
  • 7
    Jeejeebhoy F, Keith M, Freeman M, et al. Nutritional supplementation with MyoVive repletes essential cardiac myocyte nutrients and reduces left ventricular size in patients with left ventricular dysfunction. Am Heart J. 2002;143:10921100.
  • 8
    Azuma J, Hasegawa H, Sawamura A, et al. Taurine for treatment of congestive heart failure. Int J Cardiol. 1982;2:303304.
  • 9
    Azuma J, Sawamura A, Awata N. Usefulness of taurine in chronic congestive heart failure and its prospective application. Jpn Circ J. 1992;56:9599.
  • 10
    Ito T, Kimura Y, Uozumi Y, et al. Taurine depletion caused by knocking out the taurine transporter gene leads to cardiomyopathy with cardiac atrophy. J Mol Cell Cardiol. 2008;44:927937.
  • 11
    Littarru GP, Tiano L. Bioenergetic and antioxidant properties of coenzyme Q10: recent developments. Mol Biotechnol. 2007;37:3137.
  • 12
    Folkers K, Langsjoen P, Langsjoen PH. Therapy with coenzyme Q10 of patients in heart failure who are eligible or ineligible for a transplant. Biochem Biophys Res Commun. 1992;182:247253.
  • 13
    Strey CH, Young JM, Molyneux SL, et al. Endothelium-ameliorating effects of statin therapy and coenzyme Q10 reductions in chronic heart failure. Atherosclerosis. 2005;179:201206.
  • 14
    Folkers K, Vadhanavikit S, Mortensen SA. Biochemical rationale and myocardial tissue data on the effective therapy of cardiomyopathy with coenzyme Q10. Proc Natl Acad Sci U S A. 1985;82:901904.
  • 15
    Molyneux SL, Florkowski CM, George PM, et al. Coenzyme Q10: an independent predictor of mortality in chronic heart failure. J Am Coll Cardiol. 2008;52:14351441.
  • 16
    Langsjoen PH, Vadhanavikit S, Folkers K. Response of patients in classes III and IV of cardiomyopathy to therapy in a blind and crossover trial with coenzyme Q10. Proc Natl Acad Sci U S A. 1985;82:42404244.
  • 17
    Munkholm H, Hansen HH, Rasmussen K. Coenzyme Q10 treatment in serious heart failure. Biofactors. 1999;9:285289.
  • 18
    Keogh A, Fenton S, Leslie C, et al. Randomised double-blind, placebo-controlled trial of coenzyme Q, therapy in class II and III systolic heart failure. Heart Lung Circ. 2003;12:135141.
  • 19
    Belardinelli R, Mucaj A, Lacalaprice F, et al. Coenzyme Q10 and exercise training in chronic heart failure. Eur Heart J. 2006;27:26752681.
  • 20
    Morisco C, Trimarco B, Condorelli M. Effect of coenzyme Q10 therapy in patients with congestive heart failure: a long-term multicenter randomized study. Clin Investig. 1993;71:S134S136.
  • 21
    Watson PS, Scalia GM, Galbraith A, et al. Lack of effect of coenzyme Q on left ventricular function in patients with congestive heart failure. J Am Coll Cardiol. 1999;33:15491552.
  • 22
    Khatta M, Alexander BS, Krichten CM, et al. The effect of coenzyme Q10 in patients with congestive heart failure. Ann Intern Med. 2000;132:636640.
  • 23
    Sander S, Coleman CI, Patel AA, et al. The impact of coenzyme Q10 on systolic function in patients with chronic heart failure. J Card Fail. 2006;12:464472.
  • 24
    Rosenfeldt FL, Haas SJ, Krum H, et al. Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials. J Hum Hypertens. 2007;21:297306.
  • 25
    Arsenian MA. Carnitine and its derivatives in cardiovascular disease. Prog Cardiovasc Dis. 1997;40:265286.
  • 26
    Schonekess BO, Allard MF, Lopaschuk GD. Propionyl l-carnitine improvement of hypertrophied heart function is accompanied by an increase in carbohydrate oxidation. Circ Res. 1995;77:726734.
  • 27
    Masumura Y, Kobayashi A, Yamazaki N. Myocardial free carnitine and fatty acylcarnitine levels in patients with chronic heart failure. Jpn Circ J. 1990;54:14711476.
  • 28
    Serati AR, Motamedi MR, Emami S, et al. l-carnitine treatment in patients with mild diastolic heart failure is associated with improvement in diastolic function and symptoms. Cardiology. 2010;116:178182.
  • 29
    Iliceto S, Scrutinio D, Bruzzi P, et al. Effects of l-carnitine administration on left ventricular remodeling after acute anterior myocardial infarction: the l-Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) Trial. J Am Coll Cardiol. 1995;26:380387.
  • 30
    Rizos I. Three-year survival of patients with heart failure caused by dilated cardiomyopathy and l-carnitine administration. Am Heart J. 2000;139:S120S123.
  • 31
    Study on propionyl-l-carnitine in chronic heart failure. Eur Heart J. 1999;20:7076.
  • 32
    Seligmann H, Halkin H, Rauchfleisch S, et al. Thiamine deficiency in patients with congestive heart failure receiving long-term furosemide therapy: a pilot study. Am J Med. 1991;91:151155.
  • 33
    Zenuk C, Healey J, Donnelly J, et al. Thiamine deficiency in congestive heart failure patients receiving long term furosemide therapy. Can J Clin Pharmacol. 2003;10:184188.
  • 34
    Brady JA, Rock CL, Horneffer MR. Thiamin status, diuretic medications, and the management of congestive heart failure. J Am Diet Assoc. 1995;95:541544.
  • 35
    Hanninen SA, Darling PB, Sole MJ, et al. The prevalence of thiamin deficiency in hospitalized patients with congestive heart failure. J Am Coll Cardiol. 2006;47:354361.
  • 36
    Kwok T, Falconer-Smith JF, Potter JF, Ives DR. Thiamine status of elderly patients with cardiac failure. Age Ageing. 1992;21:6771.
  • 37
    Pfitzenmeyer P, Guilland JC, d’Athis P, et al. Thiamine status of elderly patients with cardiac failure including the effects of supplementation. Int J Vitam Nutr Res. 1994;64:113118.
  • 38
    Shimon I, Almog S, Vered Z, et al. Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy. Am J Med. 1995;98:485490.
  • 39
    Da Cunha S, Albanesi Filho FM, Da Cunha Bastos VL, et al. Thiamin, selenium, and copper levels in patients with idiopathic dilated cardiomyopathy taking diuretics. Arq Bras Cardiol. 2002;79:454465.
  • 40
    Rocha RM, Silva GV, De Albuquerque DC, et al. Influence of spironolactone therapy on thiamine blood levels in patients with heart failure. Arq Bras Cardiol. 2008;90:324328.
  • 41
    Smithline HA. Thiamine for the treatment of acute decompensated heart failure. Am J Emerg Med. 2007;25:124126.
  • 42
    Keith ME, Walsh NA, Darling PB, et al. B-vitamin deficiency in hospitalized patients with heart failure. J Am Diet Assoc. 2009;109:14061410.
  • 43
    Herrmann M, Kindermann I, Muller S, et al. Relationship of plasma homocysteine with the severity of chronic heart failure. Clin Chem. 2005;51:15121515.
  • 44
    Vasan RS, Beiser A, D’Agostino RB, et al. Plasma homocysteine and risk for congestive heart failure in adults without prior myocardial infarction. JAMA. 2003;289:12511257.
  • 45
    Refsum H, Smith AD, Ueland PM, et al. Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem. 2004;50:332.
  • 46
    Stanger O, Weger M. Interactions of homocysteine, nitric oxide, folate and radicals in the progressively damaged endothelium. Clin Chem Lab Med. 2003;41:14441454.
  • 47
    Herrmann W, Herrmann M, Obeid R. [Hyperhomocysteinemia and B-vitamin deficiency Current clinical aspects]. Med Monatsschr Pharm. 2006;29:291302.
  • 48
    Herrmann M, Stanger O, Paulweber B, et al. Effect of folate supplementation on N-terminal pro-brain natriuretic peptide. Int J Cardiol. 2007;118:267269.
  • 49
    Lavie CJ, Milani RV, Mehra MR, Ventura HO. Omega-3 polyunsaturated fatty acids and cardiovascular diseases. J Am Coll Cardiol. 2009;54:585594.
  • 50
    London B, Albert C, Anderson ME, et al. Omega-3 fatty acids and cardiac arrhythmias: prior studies and recommendations for future research: a report from the National Heart, Lung, and Blood Institute and Office Of Dietary Supplements Omega-3 Fatty Acids and their Role in Cardiac Arrhythmogenesis Workshop. Circulation. 2007;116:e320e335.
  • 51
    Leaf A, Weber PC. Cardiovascular effects of n-3 fatty acids. N Engl J Med. 1988;318:549557.
  • 52
    Lee JH, O’Keefe JH, Lavie CJ, et al. Omega-3 fatty acids for cardioprotection. Mayo Clin Proc. 2008;83:324332.
  • 53
    Mehra MR, Lavie CJ, Ventura HO, Milani RV. Fish oils produce anti-inflammatory effects and improve body weight in severe heart failure. J Heart Lung Transplant. 2006;25:834838.
  • 54
    Wang C, Harris WS, Chung M, et al. n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review. Am J Clin Nutr. 2006;84:517.
  • 55
    Tavazzi L, Tognoni G, Franzosi MG, et al. Rationale and design of the GISSI heart failure trial: a large trial to assess the effects of n-3 polyunsaturated fatty acids and rosuvastatin in symptomatic congestive heart failure. Eur J Heart Fail. 2004;6:635641.
  • 56
    Mozaffarian D, Bryson CL, Lemaitre RN, et al. Fish intake and risk of incident heart failure. J Am Coll Cardiol. 2005;45:20152021.
  • 57
    Lavie CJ, O’Keefe JH, Milani RV, et al. New data on the clinical impact of exercise training, fish oils, and statins in heart failure. Phys Sportsmed. 2009;37:2228.
  • 58
    Yamagishi K, Nettleton JA, Folsom AR. Plasma fatty acid composition and incident heart failure in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J. 2008;156:965974.
  • 59
    Tavazzi L, Maggioni AP, Marchioli R, et al. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:12231230.
  • 60
    Freeman LM, Rush JE, Kehayias JJ, et al. Nutritional alterations and the effect of fish oil supplementation in dogs with heart failure. J Vet Intern Med. 1998;12:440448.
  • 61
    Yamagishi K, Iso H, Date C, et al. Fish, omega-3 polyunsaturated fatty acids, and mortality from cardiovascular diseases in a nationwide community-based cohort of Japanese men and women the JACC (Japan Collaborative Cohort Study for Evaluation of Cancer Risk) Study. J Am Coll Cardiol. 2008;52:988996.
  • 62
    Fonarow GC. Statins and n-3 fatty acid supplementation in heart failure. Lancet. 2008;372:11951196.
  • 63
    Lee JH, O’Keefe JH, Bell D, et al. Vitamin D deficiency: an important, common, and easily treatable cardiovascular risk factor? J Am Coll Cardiol. 2008;52:19491956.
  • 64
    Zittermann A. Vitamin D and disease prevention with special reference to cardiovascular disease. Prog Biophys Mol Biol. 2006;92:3948.
  • 65
    Schierbeck LL, Jensen TS, Bang U, et al. Parathyroid hormone and vitamin D – markers for cardiovascular and all cause mortality in heart failure. Eur J Heart Fail. 2011;13:626632.