Fish, meat, and risk of dementia: cohort study
BMJ 2002; 325 doi: https://doi.org/10.1136/bmj.325.7370.932 (Published 26 October 2002) Cite this as: BMJ 2002;325:932All rapid responses
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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
Competing interests: No competing interests
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
Competing interests: No competing interests
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
Competing interests: No competing interests
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
Competing interests: No competing interests
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
Competing interests: No competing interests
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.
Competing interests: No competing interests
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.
Competing interests: No competing interests
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.
Competing interests: No competing interests
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.
Competing interests: No competing interests
FISH OIL, HOMOCYSTEINE and DEMENTIA
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.
127 Courser, Sutton (Qc) Canada J0E 2K0
Kilmer S. McCully.
Veterans Affairs Medical Center, West Roxbury MA 02132
USA
(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
Competing interests: No competing interests