Targeted Natural Interventions
Heart failure can be an outcome of several disease processes, thus, the best approach for heart failure includes strategies that minimize the risks of its underlying causes. This protocol will present nutritional strategies specifically studied in the context of heart failure. Several Life Extension protocols address potential contributing factors and/ or causes of heart failure; the following protocols should also be reviewed:
- Atherosclerosis and Cardiovascular Disease
- High Blood Pressure
- Cholesterol Management
- Obesity and Weight Loss
- Kidney Health
- Thyroid Regulation
Coenzyme Q10 (CoQ10)
As a critical component in the production of cellular energy within mitochondria, CoQ10 has a central role in proper cardiac function. CoQ10 is concentrated in healthy heart muscle, and its deficiency is associated with heart failure (Rosenfeldt 2007). In fact, heart failure patients with lower CoQ10 levels have up to a two-fold risk of dying compared to those with higher levels (Molyneux 2008).
As shown in several studies conducted by Life Extension Scientific Advisory Board Member Peter H. Langsjoen, MD, FACC, CoQ10 supplementation is especially important for individuals on cholesterol-lowering statin therapy (HMG CoA reductase inhibitors). Statin medications block the biosynthesis of both cholesterol and CoQ10, and these drugs have been shown to worsen heart muscle dysfunction in heart failure patients (PH Langsjoen, Langsjoen, 2005; P Langsjoen, Littarru, 2005; Folkers 1990; Silver 2004). In one study, diastolic dysfunction (heart muscle weakness) occurred in 70% of previously normal patients treated with 20 mg a day of Lipitor® for six months. This heart muscle dysfunction was reversible with 100 mg of CoQ10 three times daily (Silver 2004).
Three comprehensive reviews have investigated 19 different clinical trials on the use of CoQ10 in heart failure (Soja 1997; Sander 2006; Fotino 2013). In the most recent analysis, the results of 13 randomized controlled trials, encompassing 395 participants, revealed that CoQ10 supplementation led to a statistically significant average net increase of 3.67% in the ejection fraction. For individuals with heart failure, Life Extension suggests an optimal CoQ10 blood level of 4 μg/mL.
Groundbreaking New Study Validates CoQ10’s Benefits
The European Journal of Heart Failure recently published data from one of the most important studies to date on coenzyme Q10 – the Q-SYMBIO trial. This conclusive ten-year study showed that CoQ10 supplementation significantly improves survival for even the most severe heart failure patients while dramatically reducing incidence of hospitalization. This exciting new study shows that CoQ10 supplementation can restore deficient CoQ10 levels in patients with moderate-to-severe heart failure, extending lifespan and improving quality of life (Mortensen 2013).
The data obtained by the Q-SYMBIO investigators revealed that heart failure patients who took 100 mg of CoQ10 three times daily were:
After only three months of supplementation, the researchers detected a trend towards reduced levels of a marker of heart failure severity called N-terminal prohormone of brain natriuretic peptide (NT-proBNP), which is released from over-worked heart muscle cells (Mortensen 2013; Maisel 2002). At two years, significantly more treated patients had improved their heart failure classification than did placebo recipients (Mortensen 2013).
The study’s main endpoint measurement was the most dramatic indicator of success: only 14% of patients in the CoQ10-supplemented group had a major adverse cardiac event (defined as unplanned hospitalization for worsening heart failure, death from a cardiovascular cause, urgent heart transplantation, or artificial mechanical heart support), while 25% of those in the placebo group had a major cardiac event (Mortensen 2013).
Based on the results of this impressive study, CoQ10 offers important heart health benefits to everyone, especially cardiac patients. Ideally, the practice of cardiology will develop to include CoQ10 as a treatment for heart failure, thereby improving the lives of those living with the condition.
Pyrroloquinoline quinone (PQQ)
PQQ, an intriguing molecule that serves an important role as a cofactor for several energy-generating reactions in the mitochondria of the cell, may stimulate the production of new mitochondria (mitochondrial biogenesis) in animals through interactions with mitochondrial regulatory genes (Rucker 2009). This is important in the context of heart failure because impaired mitochondrial function has been implicated in heart failure development (Hamilton 2013).
In animal models of ischemic injury (depriving the heart muscle of oxygen), treatment or pretreatment with PQQ reduced the extent of ischemic damage and the degree of lipid peroxidation. In addition, PQQ improved ventricular function and reduced arrhythmias (irregular heartbeats) (Zhu 2004; Zhu 2006).
Fish oil is a source of omega-3 fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]), which are difficult to obtain from the diet in sufficient quantities unless large amounts of fatty fish are consumed but are nonetheless critical for several metabolic processes. Omega-3 fatty acids have been well studied for their prevention of cardiovascular disease and ability to reduce inflammation, hypertension, and the risk of cardiovascular mortality (Marik 2009; Geleijnse 2002).
A comprehensive review has investigated the utility of fish oil in improving functional capacity during heart failure. Seven trials with 825 total participants were included (dosage range of 600–4300 mg of EPA + DHA daily); results showed that left ventricular ejection fraction was increased , left ventricular end-systolic volume was decreased, and NYHA functional classification was improved in patients with non-ischemic heart failure (Xin 2012). In a study of 14 patients with NYHA Class III or IV heart failure, 8 g/day of fish oil for 18 weeks led to a statistically significant reduction in the production of TNF-α (an inflammatory protein) by 59% in the seven test patients, while TNF-α levels increased by 44% in the control group (Mehra 2006). Patients taking fish oil also saw a trend toward a reduction in the inflammatory mediator interleukin-1 (IL-1).
An association of low vitamin D levels with chronic heart failure has been suggested in a number of observational studies (Beveridge 2013; Krim 2013). For example, in a study of 548 patients re-hospitalized with heart failure, 75% of patients were vitamin D deficient (defined as <20 ng/mL for this study), and for each 10 ng/mL decrease in vitamin D levels, the risk of all-cause mortality increased by 10% (Liu 2011).
The contribution of vitamin D deficiency to the pathology of heart failure as well as its protective effects for cardiovascular health are most likely exerted by several mechanisms, including effects on the hypertensive hormone angiotensin II, influence on vascular endothelial function, effects on systemic inflammation, and impact on the risk of cardiovascular mortality (Pourdjabbar 2013; Beveridge 2013; Krim 2013). A synthetic vitamin D analog (paricalcitol) decreased inflammation and cell death in mice following experimental heart attack, while transgenic mice that lacked the vitamin D receptor showed decreased survival following a heart attack (Bae 2013).
Intervention trials of vitamin D for heart failure have had mixed results. In a prospective study, 100 patients with heart failure (NYHA class I to III) received 50 000 IU of vitamin D every week for 8 weeks, followed by 50 000 IU every month for 2 months. At the end of the study, patients on supplemental vitamin D saw improvements in exercise capacity (6 minute walk test) and reductions in NYHA heart failure scores (Amin 2013). Another intervention that used 100 000 IU twice during 10 weeks in 105 patients demonstrated no improvements in exercise capacity or quality of life scores, but the administration of 2000 IU/day for 9 months in 93 patients with heart failure showed that supplementation had an anti-inflammatory effect (Witham 2010; Schleithoff 2006).
Intervention trials using vitamin D have demonstrated modest results for lowering blood pressure. A review of 11 randomized, controlled trials, which included 716 subjects, found a small reduction in systolic (3.6 mmHg) and diastolic (3.1 mmHg) blood pressure at daily doses of 800-2900 IU of vitamin D in individuals with high blood pressure (Witham 2009). In randomized, controlled studies, the effect of vitamin D replacement showed mixed results on heart failure. In one study, it reduced the risk of mortality, but it did not show an effect on heart function, exercise capacity, or quality of life in two others (Krim 2013).
Several studies evaluating the role of L-carnitine or its analog, propionyl-L-carnitine, in heart failure have shown statistically significant increases in exercise capacity, maximum exercise time, peak heart rate, and peak oxygen consumption (Soukoulis 2009). A study that administered 30 mg/kg propionyl-L-carnitine supplementation to 30 heart failure patients demonstrated a reduced pulmonary artery pressure, improved exercise capacity, increased oxygen utilization, and reduced ventricular size (Anand 1998). Improvements in ejection fraction (13.6% after 180 days) were observed in a larger 60-patient study on NYHA class II and III heart failure patients who received 1.5 g of propionyl-L-carnitine per day in addition to their conventional treatments (digitalis and diuretics) (Mancini 1992). Another trial, which enrolled 80 patients with NYHA class III or IV heart failure caused by dilated cardiomyopathy (heart disease in which the ventricles become enlarged and unable to adequately pump blood), revealed the potential of L-carnitine to reduce mortality by demonstrating a significantly improved 3-year survival (Rizos 2000).
Two small studies investigated the use of taurine in heart failure patients. In a 2011 placebo-controlled clinical trial that enrolled 29 NYHA class II or III heart failure patients with a left ventricular ejection fraction <50% (average 29.27%), subjects were randomized to taurine supplementation (500 mg three times daily) or placebo. After 2 weeks, exercise capacity increased significantly in patients who received taurine compared to the placebo group (Beyranvand 2011). An earlier study that compared taurine (3 g/day) to low-dose CoQ10 (30 mg/day) supplementation in 17 patients with congestive heart failure (ejection fraction <50%) revealed a significant improvement in ejection fraction for the taurine group after 6 weeks, as shown by echocardiography (Azuma 1992).
Selenium is a cofactor necessary for the proper function of a number of cellular metabolic processes. In an animal model of hypertension that develops heart failure, it was shown that a selenium-free diet is associated with a high mortality (70%); however, supplementation with 50 or 100 mcg/kg of food resulted in much higher survival rates of 78% and 100%, respectively (Lymbury 2010). In humans, severe selenium deficiency has been firmly linked to a reversible form of heart failure; the first cases were reported in 1937 in China, and the condition, potentially fatal if left untreated, is known as Keshan disease (McKeag 2012; Saliba 2010). Several studies also suggested that less severe selenium deficiency may be associated with heart failure (McKeag 2012). It has been suggested that patients with heart failure not caused by poor blood flow to the heart have selenium measurements as part of their blood tests (Saliba 2010).
Hawthorn (Crataegus spp.) is a traditional cardiovascular tonic of plant origin that has been in use since the Middle Ages. Hawthorn extracts contain dozens of biologically active molecules including flavonoids and polyphenols. The hawthorn-derived phytochemicals most thoroughly studied in humans are oligomeric procyanidins (OPCs). A typical hawthorn dose provides between 30 and about 340 mg a day of procyanidins (Rigelsky 2002; Urbonaviciute 2006; Yang, Liu 2012).
Hawthorn extracts are believed to exhibit mild blood-pressure-lowering activity by multiple mechanisms, including the dilation of coronary and peripheral blood vessels, inhibition of ACE, anti-oxidative and anti-inflammatory effects, and mild diuretic activity (Schröder 2003; Furey 2008). The efficacy of hawthorn in the treatment of heart failure has been demonstrated in over 4000 patients, with significant reductions in patientsʼ subjective discomfort ratings, improved left-ventricular ejection fraction (LVEF), and increased cardiac efficiency (Koch 2011).
The SPICE trial was a large, randomized controlled study of 2681 NYHA class II or III patients with a left ventricular ejection fraction ≤35%. A 900 mg/day dose of a standardized extract from hawthorn leaves and flowers (providing 169 mg of OPCs) significantly reduced cardiac mortality, and sudden cardiac death was significantly reduced for the subgroup of patients with a left ventricular ejection fraction ≥25 % (Holubarsch 2000; Holubarsch 2008). In the HERB congestive heart failure trial, which was a placebo-controlled trial of 120 patients with NYHA class II or III heart failure, 900 mg/day of standardized hawthorn extract improved left ventricular ejection fraction in patients when compared to the control group (Zick 2009).
Arjuna (Terminalia arjuna)
The arjuna tree is native to India where its bark has been used in Ayurvedic medicine for centuries, mainly as a cardiotonic. Like hawthorn, arjunaextracts contain a wide variety of bioactive molecules, especially polyphenols and flavonoids (AMR 1999; Dwivedi 2007). Several studies provide evidence that arjuna may support various aspects of cardiovascular health.
Arjuna extracts exert anti-inflammatory effects that help combat the excessive immune response that leads to arterial plaque and blood vessel occlusions (TC 2001; Gauthaman 2001; Karthikeyan 2003). They also help modulate abnormal lipid (cholesterol) profiles that contribute to plaque formation (TC 2001; Ram 1997). In addition, arjuna extracts enhance heart muscle tone, improving its “squeeze” and increasing the amount of blood it can pump each second without exhaustion (Dwivedi 2007; Maulik 2010; Oberoi 2011).
Arjuna extracts were shown to have modest lipid-lowering effects at doses used in ancient Indian medicine (Shaila 1998). In animal studies, arjuna reduces total cholesterol, LDL cholesterol, and triglycerides; raises protective HDL; and reduces the size and number of atherosclerotic lesions in the aorta (Ram 1997; Subramaniam, Subramaniam 2011; Subramaniam, Ramachandran 2011). Humans treated with 500 mg daily of arjuna tree bark powder experienced a total cholesterol drop of 9.7% (Gupta 2001). The same dose of an extract from the bark, given every 8 hours, improved endothelial function (the ability of vital arteries to dilate and increase blood flow) by 9.3% in smokers, who typically have poor endothelial function (Bharani 2004).
D-ribose, which is a naturally-occurring pentose sugar that is a key component in the energy molecule adenosine triphosphate (ATP), may aid in energy generation and functional recovery for patients with heart failure and ischemic heart disease. Multiple preclinical studies have demonstrated that supplementation with D-ribose following myocardial ischemia (a potentially damaging event when blood flow to the heart is blocked or reduced, and the heart muscle is deprived of oxygen) enhanced the regeneration of ATP (Shecterle 2011).
In 15 patients with NYHA class II or III heart failure and chronic coronary artery disease, the administration of D-ribose (5 g, 3 times/day) resulted in improvement of cardiac functional parameters as assessed by echocardiography and significantly improved the patients’ quality of life (Omran 2003). D-ribose supplementation was reported to improve respiratory parameters during exercise in 44% of patients enrolled in a study (Vijay 2008). A second study reported significant benefits of daily oral D-ribose in NYHA class II and III patients in a double blind, randomized, crossover trial. D-ribose supplementation significantly improved left atrial functional parameters, quality of life, and physical function activity scores in this patient group (Omran 2004).
Creatine is an important component of the predominant pathway that ensures the chemical energy supply to muscle tissue. Most research focusing on creatine has targeted its potential use in skeletal muscle metabolism, but a few studies have investigated its potential to improve heart muscle energetics in cardiovascular disease (Glickman-Simon 2012).
A systematic review of creatine supplementation in patients with heart failure, ischemic heart disease, or acute myocardial infarction analyzed six randomized trials that collectively enrolled 1226 patients with heart failure. Four of the trials demonstrated a significant reduction in dyspnea (breathing difficulty) in patients with heart failure receiving creatine, creatine phosphate, or phosphocreatinine (Horjus 2011; Glickman-Simon 2012).