Title: Nutritional factors and the risk of stroke
Key words: stroke, mortality, dietary factors, Framingham studies, coronary heart disease, CHD, fruit, vegetables, cruciferous, green leafy vegetables, citrus, dietary, antioxidant, lutein, lycopene, flavonoids, fish, fish oil, vitamin C, quercitin, smoking, alcohol, hypertension, diabetes, obesity, exercise, saturated fat, refined sugar, sodium, intake, milk, dairy, calcium, magnesium, potassium, cholesterol, dyslipidaemia, statins, homocysteine, folic acid, albumin, C-reactive protein, cytokines, cardiovascular disease, inflammation, inflammatory, antioxidants, phytochemicals,
Date: Oct 2006
Author: Morgan, G
Nutritional factors and the risk of stroke
Observational studies over recent years have confirmed a steady decrease in the incidence of stroke attacks and mortality rates (Stegmayr 1998). However, the provision of medical care for strokes continues to pose a considerable burden on the health services of the developed world (Allison 1994). This review will consider the dietary factors associated with the condition.
Cross-sectional and prospective studies have now confirmed a close association with diet and the incidence of stroke. The Framingham studies have shown associations linking the classic risk factors for cardiovascular disease, both for coronary heart disease and stroke, with dietary intake of fruit and vegetables (Gillman 1995). Several prospective studies have shown reductions in stroke to be directly linked to fruit and vegetable consumption (Liu 2000, Bazzano 2002). One review, reviewing two separate studies (Joshipura 1999), showed significant risk reductions in those consuming 5 portions of fruit and vegetables a day over just one portion a day. Cruciferous, green leafy vegetables and citrus fruits, in particular, showed positive associations.
The results looking at individual dietary antioxidants have been more equivocal. Thus, low vitamin C and plasma levels have been found in several surveys (Gale 1995, Daviglus 1997, Voko 2003) and not in others (Keli 1996, Ascherio 1999). Vitamin C, vitamin E and beta carotene supplementation has been found to be ineffective (Hennekens 1996, Yusuf 2000, Heart Protection Study 2002). Other studies have shown other dietary antioxidants as possibly being more functionally important. Examples are lutein (Ascherio 1999), lycopene (Rissanen 2001), and the flavonoids (Keli 1996). It has been proposed that it is the overall synergistic effect of the many antioxidants and phytochemicals present in fruit and vegetables that are responsible for the effect (Liu 2003). Apples, for example, have been associated with a lower incidence of stroke (Knekt 2000), an effect neither attributable to their low vitamin C (Liu 2003) nor their quercitin content (Knekt 2000).
Analysis of studies such as the MONICA project has highlighted some qualitative differences between the classic risk factors common to both coronary heart disease and stroke (Stegmayr 1998). Smoking (Shaper 2004), alcohol consumption (Reynolds 2003), hypertension, diabetes, central obesity (Folsom 1999) and lack of exercise (Blair 1996) are well known risk factors. Dietary manipulation of these factors through reduced saturated fat, refined sugar and sodium intake, and a higher potassium intake, is known to reduce many of these risk factors (Liu 2000). Fish intake has been shown to be particularly effective in lowering the incidence of stroke, as little as one fish meal a month providing some protection (Gillum 1996, He 2002).
Milk and dairy consumption also shows positive effects in preventing this form of cardiovascular disease, possibly helping to modulate blood pressure through its high content of calcium, magnesium and potassium (Massey 2001). In contrast, elevated cholesterol and the dyslipidaemias have not shown the strong associations with stroke attacks compared with coronary heart disease (Bots 2002). The recent proven efficacy of statins in stroke prevention (Blauw 1997, Crouse 1997) would appear to contradict this observation but may well reflect the antioxidant and anti-inflammatory properties of these agents (Vaughan 2001).
Oxidative/inflammatory models of stroke (Ishibashi 2002) are supported by the results of homocysteine studies, a proven inflammatory and pro-oxidant metabolite and an independent risk factor for stroke (Wald 2002, Vermeer 2002). A 3 mmol/l reduction in plasma homocysteine levels has been associated with a 19% drop in stroke risk in cross-sectional studies (Homocysteine Studies Collaboration 2002). It remains to be seen whether dietary interventions, particularly increasing the intake of folic acid, will lead to significant reductions in this risk. To date, the short-term prospective VISPS trial has proved negative (Toole 2004). Other inflammatory markers are also being investigated.
Low albumin levels have been shown to be present in patients at risk of strokes (Gillum 1994) and may serve as a marker for the acute phase response seen in cardiovascular disease (Danesh 1999). Elevated C-reactive protein and cytokines have been observed both prior to and following stroke attacks (Whicher 1999, Cesari 2003). Smoking has been implicated as a possible confounding factor in the albumin studies (Shaper 2004).
In summary, the results of large observational studies have indicated that diet plays a central role in the aetiology and prevention of stroke, alongside lifestyle issues such as smoking, obesity and exercise. The evidence to date is that stroke is a complication of cardiovascular disease and is a manifestation of a chronic inflammatory process. Its evolution can be modified, and perhaps prevented, by the consumption of antioxidants and anti-inflammatory phytochemicals present in fruit and vegetables, fish, and other foodstuffs.
Given the multiple confounding factors associated with ageing, undernutrition, and chronic disease, only long-term intervention trials extending over many years will be able to resolve the theoretical and practical questions raised by such an aetiological model of stroke. Identifying and maintaining suitable cohorts over time will pose many practical problems.
1. Stegmayr B, et al. (1997) Stroke incidence and mortality correlated to stroke risk factors in the WHO MONICA Project. An ecological study of 18 populations. Stroke 28: 1367-74
2. Allison SP (1994) Is routine tomography in strokes unnecessary? Costs outweigh benefits. BMJ 309: 1499-1500
3. Gillman MW, et al. (1995) Protective effect of fruits and vegetables on development of stroke in men. JAMA 273: 1113-7
4. Liu S, et al. (2000) Fruit and vegetable intake and risk of cardiovascular disease: the Women’s Health Study. Am J Clin Nutr 72: 922-8
5. Bazzano LA, et al. (2002) Fruit and vegetable intake and risk of cardiovascular disease in US adults: the first National Health and Nutrition Examination Survey Epidemiolgic Follow-up Study. Am J Clin Nutr 76: 93-9
6. Joshipura KJ, et al. (1999) Fruit and vegetable intake in relation to risk of ischemic stroke. JAMA 282: 1233-9
7. Gale CR, Martyn CN, Winter PD, Cooper C (1995) Vitamin C and risk of death from stroke and coronary heart disease in cohort of elderly people. BMJ 310:1563-6
8. Daviglus ML, et al. (1997) Dietary vitamin C, beta carotene and 30- year risk of stroke: results from the Western Electric Study. Neuroepidemiology 16: 69-77
9. Voko Z, Hollander M, Hofman A, Koudstaal PJ, Breteler MM (2003) Dietary antioxidants and the risk of ischemic stroke: the Rotterdam Study. Neurology 61: 1273-5
10. Keli SO, Hertog MG, Feskens EJ, Kromhout D (1996) Dietary flavonoids, antioxidant vitamins, and incidence of stroke: the Zutphen study. Arch Int Med 156: 637-42
11. Ascherio A, et al. (1999) Relation of consumption of vitamin E, vitamin C, and carotenoids to risk for stroke among men in the United States. Ann Int Med 130: 963-70
12. Hennekens CH, et al. (1996) Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med 334: 1145-9 13. Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P (2000) Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 342: 154-60
14. Heart Protection Study Collaborative Group (2002) MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360: 23-33
15. Rissanen TH, et al. (2001) Low serum lycopene concentration is associated with an excess incidence of acute coronary events and stroke: the Kuopio Ischaemic Heart Disease Risk Factor Study. Br J Nutr 85: 749-54
16. Liu RH (2003) Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals. Am J Clin Nutr 78: 517S-520S
17. Knekt P, et al. (2000) Quercitin intake and the incidence of cerebrovascular disease. Eur J Clin Nutr 54: 415-7
18. Shaper AG, Wannamethee SG, Whincup PH (2004) Serum albumin and risk of stroke, coronary heart disease, and mortality: the role of cigarette smoking. J Clin Epidemiol 57: 195-202
19. Reynolds K, et al. (2003) Alcohol consumption and risk of stroke: a meta-analysis. JAMA 289: 579-88
20. Folsom AR, et al. (1999) Prospective associations of fasting insulin, body fat distribution, and diabetes with risk of ischemic stroke. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. Diabetes Care 22: 1077-83
21. Blair SN, et al. (1996) Influences of cardiorespiratory fitness and other precursors on cardiovascular disease and all-cause mortality in men and women. JAMA 276: 205-10
22. Gillum RF, Mussolino ME, Madans JH (1996) The relationship between fish consumption and stroke incidence. The NHANES 1 Epidemiologic Follow-up Study (National Health and Nutrition Examination Survey). Arch Int Med 156: 537-42
23. He K, et al. (2002) Fish consumption and risk of stroke in men. JAMA 288: 3130-6
24. Massey LK (2001) Dairy food consumption, blood pressure and stroke. J Nutr 131: 1875-8
25. Bots ML, et al. (2002) Total and HDL cholesterol and risk of stroke. EUROSTROKE: a collaborative study among research centres in Europe. J Epidemiol Commun Health 56 Suppl 1: i 19-24
26. Bluaw GJ, Lagaay AM, Smelt AH, Westendorp RG (1997) Stroke, statins, and cholesterol. A meta-analysis of randomised, placebo- controlled, double-blind trials with HMG-CoA reductase inhibitors. Stroke 28: 946-50
27. Crouse JR 3rd, Byington RP, Hoen HM, Furberg CD (1997) Reductase inhibitor monotherapy and stroke prevention. Arch Int Med 157: 1305-10
28. Vaughan CJ, Delanty N, Basson CT (2001) Do statins afford neuro- protection in patients with cerebral ishaemia and stroke? CNS Drugs 15: 589-96
29. Ishibashi N, Prokopenko O, Reuhl KR, Mirochnitchenko O (2002) Inflammatory response and glutathione peroxidase in a model of stroke. J Immunol 168: 1926-33
30. Wald DS, Law M, Morris JK (2002) Homocysteine and cardio- vascular disease: evidence on causality from a meta-analysis. BMJ 325: 1202
31. Vermeer SE, et al. (2002) Homocysteine, silent brain infarcts, and white matter lesions: The Rotterdam Scan Study. Ann Neurol 51: 285-9
32. Homocysteine Studies Collaboration (2002) Homocysteine and risk of ischaemic heart disease and stroke: a meta-analysis. JAMA 288: 2015-22
33. Toole JF, et al. (2004) Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomised controlled trial. JAMA 291: 565-75
34. Gillum RF, Ingram DD, Makuc DM (1994) Relation between serum albumin concentration and stroke incidence and death: the NHANES 1 Epidemiologic Follow-up Study. Am J Epidemiol 140: 876-88
35. Danesh J, et al. (1999) Risk factors for coronary heart disease and acute-phase proteins. A population-based study. Eur Heart Journal 20: 954-9
36. Whicher J, Biasucci L, Rifai N (1999) Inflammation, the acute phase response and atherosclerosis. Clin Chem Lab Med 37: 495-503
37. Cesari M, et al. (2003) Inflammatory markers and cardiovascular disease (the Health, Aging and Body Composition [Health ABC] Study). Am J Cardiol 92: 522-8