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Dietary links to dementia
- William B. Grant (26 October 2002)
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Is it the wine or the fish - or both?
- Erik Skovenborg (29 October 2002)
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The PAQUID study does not show a negative association between n-3 fatty acids and dementia
- Roger A Harrison (29 October 2002)
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Re: Is it the wine or the fish - or both?
- Pascale BARBERGER-GATEAU (29 October 2002)
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Fish and dementia
- Alison N Jeffery, Robert S Jeffery (30 October 2002)
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Shaky ground for fish
- Pierre Philippe (1 November 2002)
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What exactly were the hazard ratios?
- Adam Jacobs (1 November 2002)
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Re: What exactly were the hazard ratios?
- Pascale Barberger-Gateau (4 November 2002)
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Fish and Seafood should be part of our regular meals.
- Abdul Karim Al-Sheikhli (5 November 2002)
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FISH OIL, HOMOCYSTEINE and DEMENTIA
- Eddie Vos, Kilmer S. McCully MD (14 November 2002)
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William B. Grant, Atmospheric Sciences Res., NASA Langley Research Center, Hampton, VA (this work is done afterhours) 12 Sir Francis Wyatt Place, Newport News, VA 23606-3660 USA
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Pascale Barberger-Gateau and colleagues are to be congratulated on their report on the role of dietary fish in reducing the risk of dementia (1). This report adds to the growing body of literature indicating that dementia such as Alzheimer's disease (AD) and vascular dementia can be prevented through personal choices in diet and lifestyle. The first paper establishing a strong dietary link to AD was published in 1997 (2). In this study, dietary fat and energy were reported to be risk factors, while cereals and fish were reported to be risk reduction factors. These findings were supported in an editorial comment (3), and have been reviewed and updated in several subsequent publications (4-6). However, since (2) was an ecologic study, it should be checked using other approaches. Acting on a suggestion that the incidence of African-, Hispanic- and white-Americans might be due to diet (7), researchers at Columbia University conducted a 4-year cohort study and confirmed that dietary fat and energy were risk factors for AD when coupled with the APOE e4 allele, but not otherwise (8). They also confirmed cereals as a risk reduction factor. They did not have enough data to test the finding regarding dietary fish. The new study (1) now confirms the finding regarding dietary fish. (See, also, (9).) In (1) it is mentioned that meat was not found to correlate with dementia. A search of PubMed uncovers one report of increased risk of AD for meat and fish eaters compared to vegetarians (10). This report is consistent with (2) and (8). It is the author's view that inflammation is very important in the etiology of AD (11, 12) and that n-3 oils can reduce this inflammation. Inflammation may be related to oxidative stress (13), although the full reasons for the involvement of inflammation in the etiology of AD are still not understood. However, it may not be the best advice that everyone add 1-2 servings/week of fatty fish to their diet. For one thing, global fish stocks are being rapidly depleted. For another, fish bioaccumulate toxic substances including mercury. Another approach is to take non-steroidal anti-inflammatory drugs (NSAIDs) (12). However, these, too, have adverse side effects such as the risk of gastric bleeding (14). The safer course of action seems to be to adjust one's diet (3, 15) and lifestyle (16) to minimize the risk of AD, especially if one is genetically predisposed to AD (8) or over the age of 65 years. References 1. Barberger-Gateau P, Letenneur L, Deschamps V, Pérès K, Jean-François Dartigues JF, Renaud S. Fish, meat, and risk of dementia: cohort study. BMJ 2002;325:932-3. 2. Grant WB. Dietary links to Alzheimer's disease. Alz Dis Rev. 1997;2:42-55 http://www.mc.uky.edu/adreview/default.htm 3. Smith MA, Petot GJ, Perry G. Diet and Oxidative Stress: A Novel Synthesis of Epidemiological Data on Alzheimer's Disease. J Alz Dis. 1999;1(4,5):203-206. 4. Grant, WB. Dietary links to Alzheimer's disease: 1999 update. J Alz Dis. 1(4,5);197-201:1999. 5. Grant WB. Fish consumption, cancer, and Alzheimer disease, Am J Clin Nutr, letter, 2000 Feb;71:599. 6. Grant WB, Campbell A, Itzhaki RF, Savory J, The significance of environmental factors in the etiology of Alzheimer's disease, J Alz Dis 4(3), Debates from Challenging Views of Alzheimer Disease, 2002;4:179-89. 7. Grant WB. The APOE-epsilon4 allele and Alzheimer disease among African Americans, Hispanics, and Whites, JAMA, letter, Nov. 18, 1998;280:162-63. 8. Luchsinger JA, Tang MX, Shea S, Mayeux R. Caloric intake and the risk of Alzheimer disease. Arch Neurol. 2002;59:1258-63. 9. Berrino F. [Western diet and Alzheimer's disease] Epidemiol Prev. 2002 May-Jun;26:107-15. Review. Italian. 10. Giem P, Beeson WL, Fraser GE. The incidence of dementia and intake of animal products: preliminary findings from the Adventist Health Study. Neuroepidemiology. 1993;12:28-36. 11. Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, et al. Inflammation and Alzheimer's disease. Neurobiol Aging. 2000;21:383-421. 12. McGeer PL, McGeer EG. Inflammation, autotoxicity and Alzheimer disease. Neurobiol Aging. 2001;22:799-809. Review. 13. Butterfield DA, Howard B, Yatin S, Koppal T, Drake J, Hensley K, Aksenov M, Aksenova M, Subramaniam R, Varadarajan S, Harris-White ME, Pedigo NW Jr, Carney JM. Elevated oxidative stress in models of normal brain aging and Alzheimer's disease. Life Sci. 1999;65:1883-92. Review. 14. Kaufman DW, Kelly JP, Sheehan JE, Laszlo A, Wiholm BE, Alfredsson L, Koff RS, Shapiro S. Nonsteroidal anti-inflammatory drug use in relation to major upper gastrointestinal bleeding. Clin Pharmacol Ther. 1993;53:485 -94. 15. Butterfield D, Castegna A, Pocernich C, Drake J, Scapagnini G, Calabrese V. Nutritional approaches to combat oxidative stress in Alzheimer's disease. J Nutr Biochem. 2002;13:444. 16. Laurin D, Verreault R, Lindsay J, MacPherson K, Rockwood K. Physical activity and risk of cognitive impairment and dementia in elderly persons. Arch Neurol. 2001;58:498-504. |
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Erik Skovenborg, family physician Brobjergparken, DK-8250 Egaa, Denmark
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Based on data from the PAQUID study Barberger-Gateau et al have demonstrated an interesting negative relation between consumption of fish and risk of dementia in elderly people from France (1). A few years ago Orgogozo et al found a significantly reduced risk of dementia in moderate wine drinkers from the districts of Gironde and Dordogne (2). Among 291 Danish patients referred for coronary angiography in whom ischaemic heart disease was suspected, the patients with the highest intake of wine also had the highest intake of fish, as documented by a high n-3 PUFA content in adipose tissue (3). In a cross-sectional study conducted in Denmark including 23,284 men and 25,479 women aged 50-64 years wine consumption was associated with a higher intake of fish (4). In a study of a large population of female French teachers wine was the preponderant alcoholic beverage; the lighter drinkers, however, did not have healthier dietary habits than did non-drinkers (5). So the positive association between drinking wine and eating fish has not been established in a French population, however, do Barberger-Gateau et al have any data to determine whether the lower risk of developing dementia among the elderly fish eaters from southwestern France is confounded by intake of wine - or whether it is the other way about? (1) Barberger-Gateau P, Letenneur L, Deschamps V, Pérès K, Dartigues J-F, Renaud S. Fish, meat and risk of dementia: cohort study. BMJ 2002;325:932-33. (2) Orgogozo J-M, Dartigues J-F, Lafont S, Letenneur L, Commenges D, Salamon R, Renaud S, Breteler MB. Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area. Rev Neurol (Paris) 1997;153:185-92. (3) Christensen JH, Skou HA, Fog L, Hansen VE, Vesterlund T, Dyerberg J, Toft E, Schmidt EB. Marine n-3 fatty acids, wine intake, and heart rate variability in patients referred for coronary angiography. Circulation 2001;103:651-57. (4) Tjønneland A, Grønbæk M, Stripp C, Overvad K. Wine intake and diet in a random sample of 48,763 Danish men and women. Am J Clin Nutr 1999;69:49-54. (5) Kesse E, Clavel-Chapelon F, Slimani N, van Liere M. Do eating habits differ according to alcohol consumption? Results of a study of the French cohort of the European Prospective Investigation into Cancer and Nutrition (E3N-EPIC). Am J Clin Nutr 2001;74:322-27. |
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Roger A Harrison, NHS Research Fellow Bolton Primary Care Trust,, St Peter's House, Silverwell Street, Bolton BL1 1PP
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Sir Fish and Dementia Barberger-Gateau (1) and colleagues present an interesting cohort study which recruited 1,416 people aged 68 years and over with no apparent dementia at baseline. Over seven years of follow-up, eating fish or seafood at least once a week reduced the risk of dementia by 27% (adjusted hazard ratio 0.73, 95% CI 0.52, 1.03). No association was observed between the intake of meat and dementia. In their conclusions, the authors suggest that the apparent protection offered by eating fish or seafood could result from the long-chain omega-3 polyunsaturated fatty acids found in fish oils. Several important points not discussed in the paper influence the interpretation of these results. It is true that some fish and seafood are one of the main dietary sources for long chain omega-3 polyunsaturated fatty acids (LCn-3) compared with all other foods (2). However, more detailed dietary information is required before the observed benefit from eating fish can be interpreted as resulting from an increased intake of LCn-3. The amount of LCn-3 in different species of fish can vary by over ten-times. Oil-rich or fatty-fish, such as herring, mackerel and sardines contain on average 2.6g/100g of LCn-3, compared with 0.3g/100g in lean fish such as cod, haddock and plaice. The latter contain a similar amount of LCn-3 as found in chicken (0.2g/100g) (2). Mammals can convert some long-chain omega-3 from its parent alpha-linolenic fatty acid (3). This is found in green leafy vegetables, walnuts and soya. LCn-3 is also obtained from fish-oil supplements taken by many adults. Hence not all LCn-3 is obtained by eating fish and seafood. Moreover, these foods do not always provide larger amounts of LCn-3 than that obtained from other foods. Finally, the bio availability of LCn-3 after eating these foods is influenced by the intake of other fatty acids, particularly omega-6 (3). Studies examining the association between fatty acids and disease will be improved by using comprehensive dietary assessments designed specifically to estimate the habitual intake of these nutrients. Longer term intake of LCn-3 and other fatty acids can also be reliably estimated in adipose tissue or red cell membranes (4). That eating any type of fish or seafood appeared to reduce the risk of dementia suggests that this benefit could be attributed to something other than LCn-3. This requires exploration. It is also necessary to consider all dietary factors and other potential confounders such as smoking and physical activity. This will provide more information about the possible protective effect of LCn-3 from dementia and give greater confidence in the results. One area of concern not mentioned by Barberger-Gateau (1) relates to the relatively high levels of mercury found in some fish (5). This is of direct relevance to the current study as mercury intake could be positively associated with the risk of developing Alzheimer’s disease (6). This topic needs further examination in light of the current cohort study and in consideration of the overall benefits and risks to health from eating fish. 1. Barberger-Gateau P, Letenneur L, Deschamps V, Pérès K, Dartigues, J, Renaud S. Fish, meat, and risk of dementia: cohort study. BMJ 2002; 325: 932-933. 2. MAFF (1993) Fish and Fish Products. Third Supplement to the Fifth Edition of McCance & Widdowson's "The composition of foods". Royal Society of Chemistry/MAFF: Cambridge 3. Garrow J, James W, Ralph A (2000) Human Nutrition and Dietetics. Churchill Livingstone: Edinburgh 4. Hulka B, Wilcosky T, Griffith J (1990) Biological Markers in Epidemiology. Oxford University Press: Oxford 5. Egeland G, Middaugh J (1997) Balancing fish consumption benefits with mercury exposure. Science 278: 1904-1905 6. Ely, JT. Mercury induced Alzheimer's disease: accelerating incidence? Bull Environ Contam Toxicol. 2001 Dec;67(6):800-6. |
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Pascale BARBERGER-GATEAU, senior lecturer Université Bordeaux 2, 33076 Bordeaux Cedex
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We thank Dr.Skovenborg for his interest in our research and his relevant comments. Unfortunately, wine consumption was not recorded at the time of interview on fish consumption in our survey, but three years earlier. There was no association between the frequency of fish consumption and the amount of wine drunk per day three years earlier in the 1416 participants(p=0.69). When past wine consumption was added in multivariate regression models, it did not modify the relationship between fish consumption and risk of dementia in the seven subsequent years. Thus wine consumption did not explain the association between fish consumption and decreased risk of dementia in these subjects. |
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Alison N Jeffery, Postgraduate student University of Plymouth PL4 8AA, Robert S Jeffery
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Barberger-Gateau et al noted that participants who ate fish at least once a week had a significantly lower risk of developing dementia. When education was added into the model, the 95% confidence limits of the hazard ratio "slightly overlapped 1.00". Having identified this confounding variable, they concluded that the "protective" effect (their quotes) was partly explained by higher education. It might be less misleading to conclude that, having allowed for the effects of education, there was more than a 1 in 20 chance that the apparent protective effect of eating fish was spurious. Competing interests: None declared |
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Pierre Philippe, Professor University of Montreal
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This paper is based on a significant trend test between fish consumption and incidence of dementia. A similar trend test between meat consumption and incidence of dementia proved to be negative. It is, however, worth checking out the results. Thus, incidence of dementia for those who eat fish daily is 1% per year. This figure is based on 19 persons, one of whom had dementia. My point is that the study's thrust is entirely based on this unique case. Had one counted two cases of dementia instead of one, incidence would be about 2% per year, and the whole incidence trend for people consuming fish would be no more significant than in those consuming meat. Given the difficulty of diagnosis of dementia and Alzheimer's disease, the possibility evoked here is highly likely. Competing interests: None declared |
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Adam Jacobs, Director Dianthus Medical Limited, London SW19 3TZ
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Barberger-Gateau et al present hazard ratios for the risk of dementia as a function of fish and meat consumption, but do not specify what the baseline category was for the hazard ratios. Was it just those people who reported never eating fish or meat, or was it for all those who ate fish or meat less than once a week? Given the tiny numbers in their study who never ate fish or meat, I suspect they used the latter approach, although hazard ratios for comparison with those who never ate fish or meat might have been more informative. It is unfortunate that they studied a population in which fish and meat eating was almost universal. Repeating the study in a population with a higher proportion of vegetarians might give more statistically precise and therefore meaningful results. Competing interests: I am a vegetarian |
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Pascale Barberger-Gateau, senior lecturer Université Bordeaux 2, 33076 Bordeaux Cedex, France
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The baseline category used for the estimation of the hazard ratios for the risk of dementia as a function of fish or meat consumption included all those who ate respectively fish or meat less than once a week. Very few subjects never ate fish or meat indeed, so we lacked vegetarians in our sample to conduct a specific study on this group. The PAQUID participants were representative in terms of age and sex of the local community dwellers aged 65 and over at baseline. When the never consumers were excluded from the analyses, the age- and sex- adjusted hazard ratio of dementia for weekly fish consumers was almost unchanged : 0.69 with a slightly wider 95% confidence interval (0.47 to 1.00) because of the smaller sample size. For meat consumption, the p for trend was even less significant (0.83) when the 6 subjects who never ate meat were excluded. Competing interests: None declared |
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Abdul Karim Al-Sheikhli, Loc.Consultant Medical Centre,2 Manor Court Avenue,Nuneaton,CV11 5HX,,U.K.
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Dear Editor, It was very interesting to read the paper of Pascal Barberger- Gateau and colleagues,Fish,Meat and risk of dementia:cohort study,in which they show that elderly people who eat fish or sea food at least once a week are at a lower risk of developing dementia including Alzheimers Disease(1). Infact there are many studies which they show the advantage of having seafood in our meals. 1.Sjurdur Frodi Olsen and colleagues show that low consumption of seafood in early pregnancy as a risk factor for preterm delivery(2) 2.Nestel shows that eating fish is a protective for cardiovascular diseases,especially for those at risk of coronary artery disease.(3) 3.Iso etal,show that intake of fish is associated with reduced risk of thrombotic infarction in women..etc,(4) 4.Recht etal,suggest that patients with Rheumatoid Arthritis benefit from a diet rich in fish.(5) 5.Tankskanen etal,showed that eating fish has a good effect on mood as it was shown there were low depressive episodes and rates of suicides in areas with high consumption of fish,(6). 6.Cott and Hibbeln showed lack of seasonal mood changes in high consumption fish areas as in Icelanders,(7). We ought to recommend through the media that fish and seafood to be part of our daily regular meals,also further studies are required to see wheather the advantage of fish and seafood due to the fact that its contents of polyunsaturated fatty is high or other factors are important too?. References: 1.Barberger-Gateau .P,Letenneur.L,Deschamps.V, Peres.K,Francois Dartigues.J,Renaud.S,Fish,Meat,and risk of dementia:cohort study,BMJ,2002;325:932-933. 2.Sjurdur Frodi and Niels Jorgen Secher,Low consumption of Seafood in early prenancy as a risk factor for preterm delivery:Prospective study,BMJ,2002;:447-450. 3.Nestel.P,Effect of fish oil and fish on cardiovascular diseases,Curr Atheroscler,2001;Jan,3(1):68-73,Review. 4.Iso.H,Rexrode K.M,Stampfer.M.J,etal,Intake of fish and omega-3 fatty acids and risk of stroke in women,JAMA,2001,Jan 17,285(3):304-12. 5.Recht.L,Helin.P,Rasmussen.J.O,etal,J.Int.Med,1999 Jan,227(1):149-55. 6.Tanskanen.A,Hibbeln.J.R,Hinntikka.J,etal,Fish consumption ,depression and suicidality in general population,Arch G Psychiatry,2001 May,58(5):512 -3. 7.Cott.J,Hibbeln.J.R.,Lack of Seasonal mood changes in Icelanders,Am J Psychiatry,2001 Feb,158(2):328. Thanking you Yours faithfully Dr.A.K.Al-Sheikhli,MRCPsych DPM. Competing interests: None declared |
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Eddie Vos, maintains site health-heart.org 127 Courser Rd. Sutton (Qc) J0E 2K0 Canada, Kilmer S. McCully MD
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The study regarding fish, meat and dementia by Barberger-Gateau et al (1) reported a protective association with fish, rich in omega-3 fatty acids, in a population in which 170 new cases of dementia (80% Alzheimer's disease) developed. In the Framingham (U.S.) population, with a similar ratio of dementia to Alzheimer's disease, a positive (harmful) association was found with homocysteine, with a nearly doubled incidence at plasma homocysteine >14micromol/L (2). Arguably the major factor in homocysteine lowering is folic acid and indeed a negative (protective) association was found for Alzheimer's disease in the Nun study (3). However, fish and meats have little folic acid (apart from liver). Furthermore, homocysteine levels raise with methionine and lower with vitamins B2, B6 and B12, all of which are found in fish and meat at substantial but similar levels. On the other hand, as reported in a randomized controlled clinical trial (4), serum homocysteine was significantly lowered by (fish oil) omega-3 fatty acids. This observation suggests that, in addition to anti-inflammatory roles in dementia (1), fish oil has a prophylactic role in dementia/Alzheimer's disease via a homocysteine lowering pathway. Eddie Vos. Kilmer S. McCully. (1) Barberger-Gateau P, Letenneur L, Deschamps V et al. Fish, meat, and risk of dementia: cohort study. BMJ 2002;325:932-3. [PMID 12399342] (2) Seshadri S, Beiser A, Selhub J et al. Plasma Homocysteine as a Risk Factor for Dementia and Alzheimer's Disease. NEJM 2002;346:476-83. [PMID 11844848] (3) Snowdon DA, Tully CL, Smith CD et al. Serum folate and the severity of atrophy of the neocortex in Alzheimer disease: findings from the Nun study. AJCN 2000;71(4):993-8. [PMID 10731508] (4). Olszewski AJ, McCully KS. Fish oil decreases serum homocysteine in hyperlipemic men Coron Artery Dis 1993(1):53-60. [PMID 8269183] Competing interests: None declared |
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