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ApoE4 and alcohol, time to reconsider advice?

apoe4 alcohol

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#1 Dolph

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Posted 12 January 2013 - 01:27 PM


There is consensus, that for populations as a whole there is a J-formed association between moderate alcohol consumption and CVD-risk. On the other hand, advice for ApoE4-Carriers here at the forum has generally been to abstain religiously from alcohol, because for them it causes a significantly negative shift in the ratio of HDL and LDL. I think the scientific base for that advice maybe should be questioned, looking at the framingham data:

http://www.ncbi.nlm....pubmed/19717024

While the proof for the negative impact on the HDL/LDL ratio of ApoE4-Carriers is probably quite solid, drinking is STILL associated with a lower hazard ratio, at least for ischemic stroke!
As the risk for ischemic stroke is actually influenced in quite the same way by apolipoproteins as is CVD, we probably can conclude that moderate alcohol consumption is still beneficial to prevent CVD in ApoE4-Carriers?

There is also highly conflicting data if alcohol is actually detremental or beneficial for the cognitive (Alzheimer's) risk in ApoE4-Carriers. If I get that correctly, more recent studies here also rather came to the conclusion it could do more good than harm:

http://www.ncbi.nlm....pubmed/21857787

Edited by Dolph, 12 January 2013 - 01:28 PM.


#2 James Cain

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Posted 12 January 2013 - 11:15 PM

Regarding the Frammingham study, the authors say "Since DNA was not collected at baseline in this cohort, it is possible that attrition mainly due to death might have altered the study population. Such alteration could lead to biased estimate if for example subjects with E4 allele were more likely to die than those without E4 allele." They also show that alcohol has a positive correlation with HDL and reduced ischemic stroke independent of E4. This cross-sectional study is suggesting correlations that are contrary to what almost all interventional studies show.

Considering their limitations, it could be that those with E4 who have other compensatory mechanisms to gain benefit from alcohol do in fact get benefits. I've come across studies (example) that show alcohol increases only the HDL2 subfraction, which is the least protective, and potentially even negative. Still, the interventional studies are where I'd put my money, and they mostly suggest net neutral or negative.

The second study you linked concludes: "In conclusion, although analysis found that the presence of APOE ɛ4 allele eliminated any significant “protective” effect of moderate ethanol on cognitive risk, a number of other studies have found an opposite effect and our results are based on a relatively small number of ratios from just ten studies, leaving this question unsettled." Their "number of other studies" showing benefit show very little benefit, are comparatively under-powered, and are few compared to the number of studies suggesting negative outcomes.

I'd be curious to know if the benefits of a reduced cholesterol and saturated fat diet might reduce the risk risk of CVD and vascular dementia in those with ApoE4 enough for them enjoy alcohol in moderation, without significantly altering their risk. For personal motives, I sort of follow this reasoning for the time being, though I wouldn't suggest another person follow my advice. My main concern with drinking, and the reason I would cut back (I have) or stop completely, is that alcohol (actually acetaldehyde) is neurotoxic and ApoE4 seems to reduce neuronal plasticity and recovery from insult. I'd definitely avoid binge drinking, but perhaps also moderate drinking as it could lead to years of accumulating slight damage over time.

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#3 Dolph

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Posted 13 January 2013 - 12:09 AM

Hm, the Rotterdam Study is underpowered and shows very little benefit? I wouldn't call a hazard ratio of 0.46 at >1drink/week/<1drink/day very little benefit. It's actually the biggest reduction of risk found in the whole study. Bigger than the risk reduction (or actually increase) seen in non-Carriers of ApoE4! Could you explain why these results are irrelevant? (Please excuse the fact I'm actually unable to judge the power of a study/study design. I'm just a humanist and not a natural scientist...)

Edited by Dolph, 13 January 2013 - 12:14 AM.


#4 James Cain

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Posted 14 January 2013 - 01:33 PM

I hate that I can't easily post a picture of the table here, so here's the data from the Rotterdam study, Table 4.

No alcohol <1 drink per week >1 drink per week but <1 per day 1–3 drinks per day‡

All dementia
APOE*4 absent (n=99) 1·00 1·03 (0·60–1·78) 1·07 (0·62–1·85) 0·53 (0·27–1·02)
APOE*4 present (n=89) 1·00 0·71 (0·40–1·25) 0·46 (0·25–0·84) 0·56 (0·32–1·00)

Alzheimer’s disease
APOE*4 absent (n=75) 1·00 1·26 (0·67–2·37) 1·39 (0·73–2·64) 0·67 (0·31–1·46)
APOE*4 present (n=65) 1·00 0·69 (0·35–1·34) 0·46 (0·23–0·94) 0·60 (0·30–1·21)

Vascular dementia§
APOE*4 absent (n=13) 1·00 0·91 (0·24–3·43) 0·55 (0·13–2·42) 0·17 (0·02–1·55)
APOE*4 present (n=13) 1·00 0·78 (0·19–3·27) 0·26 (0·05–1·37) 0·26 (0·06–1·17)



-----------------------------
Results: Table 4 shows the relation between light-to-moderate
alcohol consumption and risk of dementia according to
absence or presence of an APOE*4 allele. Light-tomoderate
alcohol consumption seemed to be associated
with a lower risk of vascular dementia in the absence and
presence of the APOE*4 allele; however the confidence
intervals were wide owing to the small sample size. The
association with alcohol seen for overall dementia and
for Alzheimer’s disease was achieved with lower amounts
of alcohol intake in carriers of the APOE*4 allele.
However, the interaction term was not significant
(overall dementia p=0·23).
-----------------------------

Discussion: The analyses stratified by APOE genotype suggested
an interaction between this variable and alcohol
consumption. The fact that the interaction was not
significant might either reflect low power or real absence
of interaction. Evidence for a mediating effect of
apolipoprotein E in the relation between alcohol and
cognitive function has been suggested in one study,28 but
was not confirmed in another.29 Oxidation of
apolipoprotein E allows it to bind  amyloid, which is
thought to increase plaque formation among carriers of
the APOE*4 allele.30 The antioxidative effect of alcohol
could suppress this binding.31 Alternatively, since
APOE*4 is associated with lower concentrations of HDL
cholesterol and higher concentrations of LDL
cholesterol, light-to-moderate alcohol consumption
might protect against dementia by improving the lipid
profile of APOE*4 carriers.32 Further studies are needed
to clarify the relation between apolipoprotein E and
alcohol consumption.
-----------------------------
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#5 James Cain

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Posted 14 January 2013 - 01:38 PM

Hm, the Rotterdam Study is underpowered and shows very little benefit? I wouldn't call a hazard ratio of 0.46 at >1drink/week/<1drink/day very little benefit. It's actually the biggest reduction of risk found in the whole study. Bigger than the risk reduction (or actually increase) seen in non-Carriers of ApoE4! Could you explain why these results are irrelevant? (Please excuse the fact I'm actually unable to judge the power of a study/study design. I'm just a humanist and not a natural scientist...)

To be fair, I was implying that the "other studies" in total were nowhere near as convincing as the studies against alcohol with ApoE4. In truth, the argument isn't black and white, so there may be some positive effect of alcohol with ApoE4, if not for vascular reasons then for others, or vice versa. I detailed this a bit in an earlier post.
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#6 Dolph

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Posted 14 January 2013 - 01:52 PM

Hm OK, thank you for clarifying that. It's really a complex matter.
Would it be completely impossible to conclude something from such an insignificant trend in a study like that? I mean, even if there actually is a detremental effect after all, it shouldn't be too impressive given the fact it doesn't show up more obviously?

I'm not looking for an excuse to drink and I actually don't consume more than one or two beers a week at average. I just want to get a feeling about the amount of (possible) risk modification we are talking about. With smoking for example, hazard ratios for lung cancer are completely obvious and comparatively huge.
In this case here there seems to be quite some "fog of science" (at least for ordinary people like me...) and I really ask myself if it's responsible for myself to implement any lifestyle change on the base of so much uncertainty. I'm just not sure if I could do more harm than good by completely abstaining.

#7 James Cain

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Posted 02 October 2013 - 11:24 PM

This study was just published and is relevant.


The Relationship Between Midlife and Late Life Alcohol Consumption, APOE e4 and the Decline in Learning and Memory Among Older Adults.

Downer B, Zanjani F, Fardo DW.
Alcohol Alcohol. 2013 Sep 18. [Epub ahead of print]

AIMS:
The aim of the study was to determine whether the trajectory of learning and memory is modified according to an interaction between midlife or late life alcohol consumption status and the presence of one or more APOE e4 alleles.

METHODS:
This was a secondary analysis of cognitive, genetic and alcohol consumption data collected from members of the Framingham Heart Study Offspring Cohort.

RESULTS:
Light and moderate alcohol consumption during late life was associated with greater decline in learning and memory among APOE e4 carriers, whereas light and moderate alcohol consumption was associated with an increase in learning and memory among non-APOE e4 carriers. There was not a significant interaction between midlife alcohol consumption status and APOE e4 on the trajectory of learning and memory.

CONCLUSION:
Light to moderate alcohol consumption during late life may protect against a decline in learning and memory for non-APOE e4 allele carriers, but not for older adults who carry one or more APOE e4 alleles.


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#8 forever healthy

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Posted 06 July 2016 - 12:16 PM

being APOE3/4 myself i have compiled some research to build a holistic view on the implications of APOE4 for our knowledge base:

 

https://brain.foreve...splay/PUB/APOE4

 

feedback welcome

 

best michael


Edited by forever healthy, 06 July 2016 - 12:21 PM.






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