Serum β-Carotene Concentrations and the Risk of Congestive Heart Failure in Men: A Population-Based Study


Background: Congestive heart failure is a major and increasing public health problem in the Western world. Age-associated changes that lead to substantial alterations in the shape and volume of the heart and progressive dilatation and weakening of pump function have been attributed to the long-term cumulative effect of free radicals and reactive oxygen and nitrogen species.2-7 Over the past several decades, data from investigations in humans and animal models of heart failure have provided considerable evidence that free radical production and injury is increased and antioxidant reserves decreased in patients with heart failure.8 This imbalance has been referred to as oxidative stress.9

Clarification of the mechanisms responsible for the progression of heart failure is necessary in order to design specific therapeutic strategies that strengthen antioxidant defenses and halt oxidative stress-induced myocardial damage in patients with heart failure.

Several naturally-occurring phytochemicals with antioxidant and anti-inflammatory actions have been associated with the prevention of cardiovascular disease. Carotenoids are a widespread group of naturally occurring pigmented compounds that are responsible for much of the color we see in nature. They are characterized by chemical diversity and with having multiple biological functions. One of the primary biological functions of carotenoids is to serve as precursors of vitamin A.10 Carotenoids are synthesized in plants, fungi, bacteria and algae but not in humans.  In animals and humans carotenoids are obtained from their diet. Fruits and vegetables, especially yellow-orange fruits and vegetables and dark green, leafy vegetables, represent 80 – 90% of the carotenoid intake in developed countries.11 Of the more than 700 naturally occurring carotenoids identified thus far, only about 50 are present in the human diet. The carotenoids that have been most studied are β-carotene, β-cryptoxanthin, α-carotene, lycopene, lutein and zeaxanthin.11

Objective: The aim of this study carried out by researchers at the University of Eastern Finland in Kuopio, Finland was to investigate whether carotenoids are associated with the risk of congestive heart failure in Finnish men.

Methods: The study population consisted of 1,031 Finnish men aged 45 – 65 years. Baseline data, including demographic characteristics, medical history, and laboratory data (including serum lycopene, α-carotene, and β-carotene) were collected between 1991 and 1993. 

Results: The median follow-up time to death, or the end of follow up was 17.8 years (range 0.10 – 19.8 years). The investigators identified 72 congestive heart failure patients in the study group during the follow-up period. Following adjustment for age and other potential confounderss (BMI, years of education, smoking, alcohol consumption, physical activity, serum hs-CRP and serum LDL cholesterol) men in the lowest quartile of β-carotene serum concentration had a greater than 3-fold increased risk of congestive heart failure as compared to men in the highest quartile of β-carotene serum concentration. When the presence of diabetes and hypertension controlled with antihypertensive medication were included the congestive heart failure risk for men in the lowest quartile was nearly 3-fold greater than for those in the highest quartile. Concentrations of lycopene and α-carotene were not associated with increased risk following adjustment for potential confounders.

Conclusion: The main finding of this follow-up study was that low serum concentrations of β-carotene increased the risk of congestive heart failure in middle-aged Finnish men.

Comments: The intake of foods rich in carotenoids may lead to improvements in cardiovascular risk factors and reduce heart disease-related morbidity and mortality via a number of mechanisms. Table 1 shows some of the most important contributor of carotenoids to the North American diet. The antioxidant properties of carotenoids have been proposed as being the primary mechanism by which they confer their beneficial effects.

Various preclinical and clinical studies have demonstrated that carotenoids can prevent the initiation and progression of a variety of cardiovascular diseases. In 2011, Karppi et al.12showed that high concentrations of β-cryptoxanthin, lycopene and α-carotene may be associated with decreased carotid atherosclerosis in elderly men. Increased intima-media thickness of the carotid artery is a well-established marker of atherosclerosis that  corresponds to cardiovascular disease. Recent studies have suggested that greater carotid intima-media thickness is associated with reduced systolic and diastolic myocardial function13 and the development of heart failure requiring hospitalization.14

A study by Karppi et al.15 in 2012 demonstrated that low plasma levels of the carotenoids lutein and zeaxanthin were associated with an increased risk of atrial fibrillation in the elderly. Recent studies have shown that individuals with atrial fibrillation are at significant risk of morbidity, with more than two thirds experiencing stroke, heart failure or death.16 Atrial fibrillation is common in the natural history of heart failure and predicts a poor prognosis.17 The authors suggest that the intake of foods rich in carotenoids may provide protection from atrial fibrillation.

Table 1. Important contributors of carotenoids in North American diet (data adapted from Rao et al. and Krinsky et al.)18;19

CarotenoidFood Source
β-CaroteneCarrots (raw)
Mangos (canned)
Sweet potato (cooked)
Pumpkin (canned)
Kale (cooked)
Spinach (raw, cooked)
Winter butternut squash
Swiss chard (raw)
Apricots (raw)
Pepper, red (raw, cooked)
Cantaloupe (raw)
Broccoli (cooked)
Lettuce, romaine (raw)
α-CaroteneCarrots (cooked)
LycopeneTomato paste
Tomato sauce
Tomato ketchup
Tomato juice
Tomatoes (raw, cooked)
β-CryptoxanthinTangerine (raw)
Papaya (raw)
Lutein and ZeaxanthinKale (cooked)
Spinach (raw, cooked)
Lettuce, romaine (raw)
Broccoli (raw, cooked)
Summer squash , zucchini
Corn, sweet (cooked, canned)
Peas, green (canned)
Brussels sprouts (cooked)

A recent study in otherwise healthy patients with mostly mild obstructive sleep apnea by Day et al.20  revealed that plasmas from these patients had significantly lower levels of all-trans β-carotene and 9-cis β-carotene (both are naturally occurring forms of β-carotene and precursors to vitamin A) compared with control subjects. Obstructive sleep apnea has been demonstrated to increase the risk for several acute and chronic cardiovascular conditions such as hypertension, heart failure, arrhythmias, renal disease, stroke, myocardial infarction and sudden death.21

A 2011 study by Koh at al.{NCVD79}demonstrated a significant, inverse association between the plasma levels of the carotenoids β-cryptoxanthin and lutein, and the risk of developing acute myocardial infarction. A similar study by Karppi et al.{NCVD77} showed that low serum concentrations of β-carotene and lycopene may increase the risk of acute myocardial infarction in men. Myocardial infarction jeopardizes cardiac function by reducing muscle contractility. The muscle tissue in the infarcted area dies and is replaced by scar tissue which is no longer able to contribute to the pumping activity of the heart. As a result, overall cardiac performance is lessened. Furthermore, the remaining healthy heart muscle outside of the infarcted area must compensate for the loss of function and this increased workload can initiate changes that eventually end in heart failure.22

Reference List

  1. Karppi J, Kurl S, M+ñkikallio TH, Ronkainen K, Laukkanen JA. Serum +¦-carotene concentrations and the risk of congestive heart failure in men: A population-based study [abstract]. International Journal of Cardiology 2013;
  2. Lakatta EG, Levy D. Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises: Part I: Aging Arteries: A ΓÇ£Set UpΓÇ¥ for Vascular Disease. Circulation 2003;107:139-146.
  3. Lakatta EG, Levy D. Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises: Part II: The Aging Heart in Health: Links to Heart Disease. Circulation 2003;107:346-354.
  4. Lakatta EG. Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises: Part III: Cellular and Molecular Clues to Heart and Arterial Aging. Circulation 2003;107:490-497.
  5. Bruckdorfer KR. Antioxidants and CVD. Proceedings of the Nutrition Society 2008;67:214-222.
  6. Singh P, Chandra A, Mahdi F, Roy A, Sharma P. Reconvene and Reconnect the Antioxidant Hypothesis in Human Health and Disease. Indian Journal of Clinical Biochemistry 2010;25:225-243.
  7. Tsutsui H, Kinugawa S, Matsushima S. Oxidative stress and heart failure. American Journal of Physiology – Heart and Circulatory Physiology 2011;301:H2181-H2190.
  8. Keith M, Geranmayegan A, Sole MJ et al. Increased Oxidative Stress in Patients With Congestive Heart Failure. J Am Coll Cardiol 1998;31:1352-1356.
  9. Y++cel Da, Aydo-¦du S, +çehreli S et al. Increased oxidative stress in dilated cardiomyopathic heart failure. Clin Chem 1998;44:148-154.
  10. Hernandez-Marin E, Galano A, Mart+¡nez A. Cis Carotenoids: Colorful Molecules and Free Radical Quenchers. J.Phys.Chem.B 2013;117:4050-4061.
  11. Maiani G, Periago Cast+¦n MaJs, Catasta G et al. Carotenoids: Actual knowledge on food sources, intakes, stability and bioavailability and their protective role in humans. Mol.Nutr.Food Res. 2009;53:S194-S218.
  12. Karppi J, Kurl S, Laukkanen JA, Rissanen TH, Kauhanen J. Plasma carotenoids are related to intima ΓÇô media thickness of the carotid artery wall in men from eastern Finland. Journal of Internal Medicine 2011;270:478-485.
  13. Fernandes VnRS, Polak JF, Edvardsen T et al. Subclinical Atherosclerosis and Incipient Regional Myocardial Dysfunction in Asymptomatic Individuals: The Multi-Ethnic Study of Atherosclerosis (MESA). J Am Coll Cardiol 2006;47:2420-2428.
  14. Engstr+¦m G, Melander O, Hedblad B. Carotid Intima-Media Thickness, Systemic Inflammation, and Incidence of Heart Failure Hospitalizations. Arterioscler Thromb Vasc Biol 2009;29:1691-1695.
  15. Karppi J, Kurl S, M+ñkikallio T, Ronkainen K, Laukkanen J. Low levels of plasma carotenoids are associated with an increased risk of atrial fibrillation. Eur J Epidemiol 2013;28:45-53.
  16. Lubitz SA, Moser C, Sullivan L et al. Atrial Fibrillation Patterns and Risks of Subsequent Stroke, Heart Failure, or Death in the Community. Journal of the American Heart Association 2013;2:
  17. Zakeri R, Chamberlain AM, Roger VrL, Redfield MM. Temporal Relationship and Prognostic Significance of Atrial Fibrillation in Heart Failure Patients With Preserved Ejection Fraction: A Community-Based Study. Circulation 2013;128:1085-1093.
  18. Rao AV, Rao LG. Carotenoids and human health. Pharmacological Research 2007;55:207-216.
  19. Krinsky NI, Johnson EJ. Carotenoid actions and their relation to health and disease. Molecular Aspects of Medicine 2005;26:459-516.
  20. DAY RM, MATUS IA, SUZUKI YJ et al. Plasma levels of retinoids, carotenoids and tocopherols in patients with mild obstructive sleep apnoea. Respirology 2009;14:1134-1142.
  21. Fava C, Montagnana M, Favaloro E, Guidi G, Lippi G. Obstructive Sleep Apnea Syndrome and Cardiovascular Diseases. Semin Thromb Hemost 2011;37:280-297.
  22. Bui AL, Horwich TB, Fonarow GC. Epidemiology and risk profile of heart failure. Nature Reviews Cardiology 2011;8:30-41.

1 thought on “Serum β-Carotene Concentrations and the Risk of Congestive Heart Failure in Men: A Population-Based Study”

Leave a Comment