The Deadly Link Between Heart Disease and Alzheimer’sJune 2007
By Edward R. Rosick, DO, MPH, DABHM
Omega-3 Fatty Acids: Vital for Heart and Brain Health
Fish oil contains eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), two essential fatty acids that are critically important in lipid metabolism, blood pressure regulation, immune modulation, and brain development. Without consumption of food or supplements containing omega-3 fatty acids, good health is simply not possible.
There is now indisputable evidence that supplementing with omega-3 fatty acids can help prevent and treat a variety of chronic diseases, including heart disease and Alzheimer’s. One of the first large-scale studies on this subject, published in 1997, looked at the effects of fish consumption on coronary heart disease and the incidence of heart attacks in 1,822 men.29 Men who consumed diets rich in cold-water fish, an abundant source of omega-3 fatty acids, had a greatly reduced risk of heart disease or dying from a heart attack.
In addition to preventing heart disease, omega-3 fatty acids may greatly benefit those with existing heart disease. Based on a review of thousands of scientific publications, cardiovascular health experts now recommend regular consumption of EPA and DHA for cardiovascular disease prevention, treatment after a myocardial infarction, prevention of sudden death, and secondary prevention of cardiovascular disease. Furthermore, these experts now suggest that low levels of omega-3 fatty acids in the body should be considered a new risk factor for sudden cardiac death.30
Besides protecting against heart disease, omega-3 fatty acids can also help protect against devastating dementia as occurs in Alzheimer’s disease. A study published last year in the Archives of Neurology examined 899 men and women over an average of more than nine years to determine whether DHA had a protective effect against Alzheimer’s and other forms of demenia.31 Subjects who had the highest DHA levels in their bloodstream had a marked 47% lower risk of developing all-cause dementia, and a modestly reduced risk of developing Alzheimer’s disease.
Omega-3 fatty acids may also benefit those already suffering impaired cognitive function. In a study of the effects of DHA and EPA supplementation in patients with mild to moderate Alzheimer’s disease who were undergoing pharmaceutical therapy, six or more months of omega-3 supplementation slowed the rate of cognitive decline in those with very mild Alzheimer’s disease.32
Animal models of Alzheimer’s disease provide tantalizing clues as to how omega-3 fatty acids may offset cognitive decline. In a recent study published in the Journal of Neuroscience, consuming DHA-enhanced feed decreased amyloid-beta levels in the brains of mice by a remarkable 70%, prompting the study authors to conclude that “dietary DHA could be protective against [amyloid-beta] production, accumulation, and potential downstream toxicity.”33 Omega-3 fatty acids may likewise protect the brain against the effects of inadequate oxygen supply. Rats with higher dietary intake of omega-3 fatty acids were protected against the effects of experimentally induced cerebral hypoxia, as evidenced by their improved ability to navigate a maze compared to control animals.34
Vinpocetine Protects Against Hypoxia, Vascular Dementia
Vinpocetine, a botanical agent derived from the periwinkle flower Vinca minor, has been used to help manage disorders of the central nervous system for several decades. Vinpocetine is remarkable in its ability to increase the flow of oxygen-rich blood to the brain and enhance the brain’s utilization of glucose as fuel.35 These characteristics strongly suggest that vinpocetine could have applications in fighting conditions associated with diminished blood flow, including heart disease and possibly Alzheimer’s disease.
Vinpocetine works via several different mechanisms of action, all of which may have important benefits for managing vascular conditions. A potent antioxidant, vinpocetine works as a vasodilator to relax the smooth muscles lining blood vessels, thus enhancing blood flow. Vinpocetine also decreases platelet and red blood cell aggregation while increasing the membrane flexibility of red blood cells, effects that could help prevent blood clots that can trigger heart attack or stroke. Vinpocetine likewise displays powerful neuroprotective effects, protecting cells against damage induced by hypoxia.36
Double-blind studies have shown that vinpocetine supplementation yields improvements in patients with mild to moderate vascular dementia (caused by inadequate blood flow to the brain).37-39 In Europe and Japan, vinpocetine is widely used as an adjunct therapy to treat ischemic stroke, a condition in which the brain suffers from low levels of oxygen.40
With the recent recognition that low levels of brain oxygenation are a hallmark of Alzheimer’s disease, future studies may well demonstrate vinpocetine’s ability to help fight the pathological processes involved in Alzheimer’s disease.
Slowly but inexorably, main-stream medicine is inching toward integrative medicine’s recognition that the mind and body are one. In the case of heart disease and Alzheimer’s disease, it is increasingly clear that nutritional and other strategies designed to preserve and improve heart health may hold significant benefits for brain health as well. Accumulating evidence suggests that nutritional strategies to combat heart disease and hypoxia may be essential elements in any program that seeks to avoid the heart-wrenching consequences of Alzheimer’s disease.
Edward R. Rosick, DO, MPH, DABHM, is a board-certified physician in preventive and holistic medicine, and assistant professor of medicine at Michigan State University.
1. Available at: http://www.americanheart.org/presenter.jhtml?identifier=4478. Accessed April 4, 2007.
2. Available at: http://www.alz.org/national/documents/Report_2007FactsAndFigures.pdf. Accessed April 4, 2007.
3. Grundman M, Thal LJ. Treatment of Alzheimer’s disease: rationale and strategies. Neurol Clin. 2000 Nov;18(4):807-28.
4. Mayeux R, Sano M. Treatment of Alzheimer’s disease. N Engl J Med. 1999 Nov 25;341(22):1670-9.
5. Moreira PI, Smith MA, Zhu X, et al. Oxidative stress and neurodegeneration. Ann NY Acad Sci. 2005 Jun;1043:545-52.
6. de la Torre JC. Vascular basis of Alzheimer’s pathogenesis. Ann N Y Acad Sci. 2002 Nov;977:196-215.
7. Sun X, He G, Qing H, et al. Hypoxia facilitates Alzheimer’s disease pathogenesis by up-regulating BACE1 gene expression. Proc Natl Acad Sci USA. 2006 Dec 5;103(49):18727-32.
8. Aliev G, Smith MA, Obrenovich ME, de la Torre JC, Perry G. Role of vascular hypoperfusion-induced oxidative stress and mitochondria failure in the pathogenesis of Azheimer disease. Neurotox Res. 2003;5(7):491-504.
9. Ni JW, Matsumoto K, Li HB, Murakami Y, Watanabe H. Neuronal damage and decrease of central acetylcholine level following permanent occlusion of bilateral common carotid arteries in rat. Brain Res. 1995 Mar 6;673(2):290-6.
10. Available at: http://www.emedicine.com/neuro/topic13.htm. Accessed April 5, 2007.
11. Singh KK. Mitochondrial dysfunction is a common phenotype in aging and cancer. Ann NY Acad Sci. 2004 Jun;1019:260-4.
12. Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA. 1993 Sep 1;90(17):7915-22.
13. Perrig WJ, Perrig P, Stahelin HB. The relation between antioxidants and memory performance in the old and very old. J Am Geriatr Soc. 1997 Jun;45(6):718-24.
14. Zandi PP, Anthony JC, Khachaturian AS, et al. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study. Arch Neurol. 2004 Jan;61(1):82-8.
15. Kapelusiak-Pielok M, Adamczewska-Goncarzewicz Z, Dorszewska J, Grochowalska A. The protective action of alpha-tocopherol on the white matter lipids during moderate hypoxia in rats. Folia Neuropathol. 2005;43(2):103-8.
16. Delmas D, Jannin B, Latruffe N. Resveratrol: preventing properties against vascular alterations and ageing. Mol Nutr Food Res. 2005 May;49(5):377-95.
17. Hung LM, Chen JK, Huang SS, Lee RS, Su MJ. Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes. Cardiovasc Res. 2000 Aug 18;47(3):549-55. 18. Russo A, Palumbo M, Aliano C, et al. Red wine micronutrients as protective agents in Alzheimer-like induced insult. Life Sci. 2003 Apr 11;72(21):2369-79.
19. Savaskan E, Olivieri G, Meier F, et al. Red wine ingredient resveratrol protects from beta-amyloid neurotoxicity. Gerontology. 2003 Nov;49(6):380-3.
20. Zamin LL, llenburg-Pilla P, Argenta-Comiran R, et al. Protective effect of resveratrol against oxygen-glucose deprivation in organotypic hippocampal slice cultures: Involvement of PI3-K pathway. Neurobiol Dis. 2006 Oct;24(1):170-82.
21. Marambaud P, Zhao H, Davies P. Resveratrol promotes clearance of Alzheimer’s disease amyloid-beta peptides. J Biol Chem. 2005 Nov 11;280(45):37377-82.
22. Jonas W, Levin J. Essentials of Complementary and Alternative Medicine. Philadelphia, PA: Lippincott Williams and Wilkins; 1999.
23. DeFeudis FV, Drieu K. Ginkgo biloba extract (EGb 761) and CNS functions: basic studies and clinical applications. Curr Drug Targets. 2000 Jul;1(1):25-58.
24. Bastianetto S, Ramassamy C, Dore S, et al. The Ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell death induced by beta-amyloid. Eur J Neurosci. 2000 Jun;12(6):1882-90.
25. Yao Z, Drieu K, Papadopoulos V. The Ginkgo biloba extract EGb 761 rescues the PC12 neuronal cells from beta-amyloid-induced cell death by inhibiting the formation of beta-amyloid-derived diffusible neurotoxic ligands. Brain Res. 2001 Jan 19; 889(1-2):181-90.
26. Bridi R, Crossetti FP, Steffen VM, Henriques AT. The antioxidant activity of standardized extract of Ginkgo biloba (EGb 761) in rats. Phytother Res. 2001 Aug;15(5):449-51.
27. Chandrasekaran K, Mehrabian Z, Spinnewyn B, et al. Neuroprotective effects of bilobalide, a component of Ginkgo biloba extract (EGb 761) in global brain ischemia and in excitotoxicity-induced neuronal death. Pharmacopsychiatry. 2003 Jun;36 Suppl 1S89-S94.
28. Logani S, Chen MC, Tran T, Le T, Raffa RB. Actions of Ginkgo Biloba related to potential utility for the treatment of conditions involving cerebral hypoxia. Life Sci. 2000 Aug 11;67(12):1389-96.
29. Daviglus ML, Stamler J, Orencia AJ, et al. Fish consumption and the 30-year risk of fatal myocardial infarction. N Engl J Med. 1997 Apr 10;336(15):1046-53.
30. von Schacky C, Harris WS. Cardiovascular benefits of omega-3 fatty acids. Cardiovasc Res. 2007 Jan 15;73(2):310-5.
31. Schaefer EJ, Bongard V, Beiser AS, et al. Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study. Arch Neurol. 2006 Nov;63(11):1545-50.
32. Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, et al. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Arch Neurol. 2006 Oct;63(10):1402-8.
33. Lim GP, Calon F, Morihara T, et al. A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J Neurosci. 2005 Mar 23;25(12):3032-40.
34. de Wilde MC, Farkas E, Gerrits M, Kiliaan AJ, Luiten PG. The effect of n-3 polyunsaturated fatty acid-rich diets on cognitive and cerebrovascular parameters in chronic cerebral hypoperfusion. Brain Res. 2002 Aug 30;947(2):166-73.
35. Bonoczk P, Gulyas B, dam-Vizi V, et al. Role of sodium channel inhibition in neuroprotection: effect of vinpocetine. Brain Res Bull. 2000 Oct;53(3):245-54.
36. [No authors listed]. Vinpocetine. Monograph. Altern Med Rev. 2002 Jun;7(3):240-3.
37. Balestreri R, Fontana L, Astengo F. A double-blind placebo controlled evaluation of the safety and efficacy of vinpocetine in the treatment of patients with chronic vascular senile cerebral dysfunction. J Am Geriatr Soc. 1987 May;35(5):425-30.
38. Hindmarch I, Fuchs HH, Erzigkeit H. Efficacy and tolerance of vinpocetine in ambulant patients suffering from mild to moderate organic psychosyndromes. Int Clin Psychopharmacol. 1991;6(1):31-43.
39. Nicholson CD. Pharmacology of nootropics and metabolically active compounds in relation to their use in dementia. Psychopharmacology (Berl). 1990;101(2):147-59.
40. Feigin VL, Doronin BM, Popova TF, Gribatcheva EV, Tchervov DV. Vinpocetine treatment in acute ischaemic stroke: a pilot single-blind randomized clinical trial. Eur J Neurol. 2001 Jan;8(1):81-5.