What Works for Congestive Heart Failure?

Congestive heart failure (chf) is the most common reason for hospitalization among elderly Americans. Coenzyme Q10 (CoQ10), hawthorn extract, and L-carnitine each have been promoted in the lay press as natural alternatives for treating CHF and promoting general cardiovascular fitness.

Coenzyme Q10

CoQ10 is a fat-soluble antioxidant produced by the body and found in small amounts in most foods. A member of the quinone family, CoQ10 has a structure similar to vitamins E and K, but it is not classified as a vitamin.

CoQ10 is an essential component of the mitochondria and plays a role in ATP production.1 CoQ10 is a carrier for two-electron transfer within the lipid phase of the mitochondrial membrane, and it is vital for proper energy production.2 CoQ10 also has shown antioxidant properties in membranes, the ability to stabilize membranes,2,3 and a role in oxidative phosphorylation.4

Clinical studies have shown that patients with New York Heart Association (NYHA) Class III-IV CHF have significantly lower blood and tissue levels of CoQ10 than NYHA Class I-II patients or healthy controls.5,6 Statin drugs may also decrease CoQ10 levels and represent a likely comorbidity for CHF patients.

The most rigorous trial that reported clinical outcomes was a one-year, placebo-controlled study of CoQ10 in 651 NYHA Class III or IV CHF patients.7 This study found a significant decrease in the number of hospitalizations, episodes of pulmonary edema, and episodes of cardiac asthma. Although there was no difference in death rates, the relative risk reductions range from 38-61% and the absolute risk reductions range from 14-31%.

No adverse effects were documented in this study; other studies have shown mild, transient nausea,8 epigastric discomfort, and loss of appetite.9 Safety in pregnant and lactating women has not been demonstrated.

CoQ10 is available as tablet or capsule; however, the soft gel capsule provides higher bioavailability of this fat-soluble antioxidant. The dose used in the largest clinical trial was 2 mg/kg/d,7 but reported doses vary from 50-150 mg/d.

CoQ10 appears to be a promising agent in the symptomatic treatment of CHF. Although a recent study failed to show benefit from CoQ10 supplementation,9 a recent review10 and meta-analysis11 have shown benefit. A mortality benefit has not been established and comparative studies with conventional therapies regarding clinical outcomes are needed. Until CoQ10 is shown to reduce mortality in CHF, ACE inhibitors, diuretics, digoxin, and beta blockers remain the cornerstones of therapy.

Hawthorn Extract (Crataegus spp.)

Although the leaves, flowers, and berries of hawthorn are used, the flowers have the most cardioactive activity. The flavonoids and oligomeric procyanidins have been shown in animal studies to be the most pharmacologically active constituents of the whole extract.

Of five placebo-controlled studies of hawthorn, four showed subjective improvement in symptoms by patient and physician reports.12 A captopril-controlled study showed improved exercise tolerance in both groups and no statistical difference between captopril and hawthorn.13 All six studies showed demonstrated improvement in objective measures, either pressure-rate product, or improved left ventricular ejection fraction.

Although hawthorn extracts have reduced blood pressure in rare instances, they are exceedingly safe in clinical practice and no specific toxicities have been reported.12 Some herbalists advise monitoring digoxin levels in patients on the medication who then begin taking hawthorn extract.

Standardized extracts, in capsules or tincture forms, are typically prepared with a defined content of flavonoids (2.2%), oligomeric procyanidins (18.75%), or total flavonoids (adjusted to 10 mg). The dose range is 160-900 mg of standardized extract in divided doses.

L-Carnitine

In 1986 the FDA approved L-carnitine for use in primary carnitine deficiency. Secondary carnitine deficiencies occur with chronic total parenteral nutrition, dialysis, and valproic acid use. Carnitine supplements have been studied in these conditions as well as for chronic fatigue syndrome, hypercholesterolemia, AIDS, and enhancement of athletic performance.

Urinary carnitine excretion is increased in CHF.14 A randomized double-blind controlled trial studied 60 patients with CHF (ejection fraction less than 50%, NYHA Class II or III) for 180 days.15 Subjects received either propionyl-L-carnitine (50 mg tid) or placebo. During the study only digoxin and diuretics were allowed. Significant improvements in maximum exercise times and ejection fractions were reported (e.g., ejection fraction 41-47%). Two other small trials reported similar results. However, a recently completed, unpublished large-scale trial of propionyl-L-carnitine in CHF failed to show improvement in exercise capacity.16 Unfortunately, it is not clear whether L-carnitine provides any benefit beyond well-established therapies.

Carnitine frequently causes nausea, pyrosis, dyspepsia, and diarrhea. High doses have resulted in a body odor like rotting fish. A myasthenia gravis-like syndrome was seen in dialysis patients receiving dL-carnitine but not with L-carnitine. Taking valproic acid may lead to carnitine deficiency; the effects of valproic acid may be more severe in individuals with lowered carnitine levels.17 Concomitant use of carnitine with warfarin may potentiate warfarin's anticoagulant effects.17

L-carnitine is readily available, but prices vary dramatically. Most marketers suggest 1-2 g/d, which was the dose most commonly used in clinical trials. v

For more information on these three supplements, see Alternative Medicine Alert, March 1998, August 1998, and July 1999, or call Customer Service at (800) 688-2421.

References

1. Hendler S. The Doctor's Vitamin and Mineral Encyclopedia. New York: Simon & Schuster; 1990.

2. Crane FL, et al. The essential functions of Coenzyme Q10. Clin Investig 1993;71(8 suppl):S55-S59.

3. Spigset O. Coenzyme Q10 in the treatment of heart failure. Are any positive effects documented? Tidsskr Nor Laegeforen 1994;114:939-942.

4. Greenberg S. Coenzyme Q10: A new drug for cardiovascular disease. J Clin Pharmacol 1990;30:596-608.

5. Folkers K, et al, eds. Biomedical and Clinical Aspects of Coenzyme Q10. Vol. 1-4. Amsterdam: Elsevier Science Publishers; Vol. 1, 1977; Vol. 2, 1980; Vol. 3, 1982; Vol. 4, 1984.

6. Mortensen SA. Coenzyme Q10: Clinical benefits with biochemical correlates suggesting a scientific breakthrough in the management of chronic heart failure. Int J Tissue React 1990;12:155-162.

7. Morisco C, et al. Effect of coenzyme Q10 therapy in patients with congestive heart failure: A long-term multicenter randomized study. Clin Investig 1993;71(8 suppl):S134-S136.

8. Langsjoen H, et al. Usefulness of coenzyme Q10 in clinical cardiology: A long-term study. Mol Aspects Med 1994;15: S165-S175.

9. Watson PS, et al. Lack of effect of coenzyme Q on left ventricular function in patients with congestive heart failure. J Am Coll Cardiol 1999;33:1549-1552.

10. Langsjoen PH, Langsjoen AM. Overview of the use of CoQ10 in cardiovascular disease. Biofactors 1999;9:273-284.

11. Soja AM, Mortensen SA. Treatment of congestive heart failure with coenzyme Q10 illuminated by meta-analyses of clinical trials. Mol Aspects Med 1997;18(suppl):S159-S168.

12. Busse W. Standardized Crataegus extract clinical monograph. Quarterly Rev Nat Med 1996;Fall:189-197.

13. Tauchert M, et al. Effectiveness of the hawthorn extract LI 132 compared with the ACE inhibitor captopril: Multicenter double-blind study with 132 NYHA stage II patients. Munch Med 1994;136(suppl 1):S27-S33.

14. Matsui S, et al. Urinary carnitine excretion in patients with heart failure. Clin Cardiol 1994;17:301-305.

15. Mancini M, et al. Controlled study on the therapeutic efficacy of propionyl-L-carnitine in patients with congestive heart failure. Arzneimittelforschung 1992;42:1101-1104.

16. Ferrari R, De Giuli F. The propionyl-L-carnitine hypothesis: An alternative approach to treating heart failure. J Card Fail 1997;3:217-224.

17. Natural Medicines Comprehensive Database [database online]. Stockton, CA: Therapeutic Research Center, Inc., 2000.