Apo-E, Alcohol, and LDL Cholesterol – The Framingham Offspring Study

Framingham offspring

I first came across this study when I read about Steve Kirsch’s experience with drinking alcohol to lower his LDL cholesterol after finding out he has an Apo E2 allele.  I figured that it’d be a good idea for me to look at the actual study he referred to and was pleasantly surprised to discover that it was free to the public.

In the introduction the authors summarize what is currently known about the ApoE gene and how it relates to LDL cholesterol:

  • Apo E3/E3 constitutes the majority of the population.  Expresses what is considered ‘normal LDL’
  • Apo E2 people (E2/E2 or E2/E3) have lower LDL
  • Apo E4 people (E4/E4 or E4/E3) have higher LDL

The purpose of this study was to examine the relationship between how alcohol affects LDL cholesterol with respect to the different Apo E genotypes.

This study was a cross-sectional study where they examined data that was obtained from the Framingham Offspring study.  As with all epidemiological studies, causation CANNOT be established.  ONLY correlations and associations can be drawn from these results.

Subjects

Nearly all subjects were white (so if you’re non-white this may not apply to you)

All the subjects were free of coronary heart disease and were not taking lipid-lowering medications or estrogen replacement therapy.

It’s interesting to note the percentage breakdowns of the Apo E genotype:

There were a total of 1014 men.

Apo E2: 125 (12%)
Apo E3: 691 (68%)
Apo E4: 198 (20%)

There were a total of 1133 women.

Apo E2: 170 (15%)
Apo E3: 736 (65%)
Apo E4: 227 (20%)

In sum, there were a total of 2147 subjects.

Apo E2: 295 (14%)
Apo E3: 1427 (66%)
Apo E4: 425 (20%)

These distributions are in complete agreement with what is known about Apo E genetics in other studies out there too.

The researchers divided the participants into drinkers vs non-drinkers and then further defined them as: no intake (0gm/day alcohol), moderate intake (<26.4 gm/day for men and <13.2 gm/day for women), and high intake (>26.4 gm/day for men and >13.2 gm/day for women), depending on how much they reportedly drank.

The authors do state that a limitation of this study is that it is based on surveys and therefore self-reported and subject to bias.

Results

Framingham Offspring Table

I used this calculator to convert from mmol/L to mg/dL.

Males

Let’s look at what they found in males:

In male nondrinkers the mean LDL-C was:

Apo E2: 3.28 mmol/L (126.8 mg/dL)
Apo E3: 3.30 mmol/L (127.6 mg/dL)
Apo E4: 3.09 mmol/L (119.5 mg/dL)

In male drinkers the mean LDL-C was:

Apo E2: 2.84 mmol/L (109.8 mg/dL)
Apo E3: 3.38 mmol/L (130.7 mg/dL)
Apo E4: 3.54 mmol/L (136.9 mg/dL)

With this data we can see a few things:

  1. In male non-drinkers, the LDL-C of those with Apo E2 vs Apo E3 is virtually identical. This goes against the general understanding that carriers of Apo E2 typically have a lower LDL-C compared to Apo E3 carriers.
  2. In male non-drinkers, the LDL-C of Apo E4 carriers is actually lower than that of APO E3 carriers, which also goes against the general understanding that Apo E4 carriers typically have a higher LDL-C compared to Apo E3 carriers.
  3. In male drinkers, the general understanding actually holds true. Apo E2 carriers have a lower LDL-C than Apo E3 carriers AND Apo E4 carriers have a higher LDL-C than Apo E3 carriers.

Now let’s look at what they found in females:

 Females

In female nondrinkers the mean LDL-C was:

Apo E2: 2.95 mmol/L (114.1 mg/dL)
Apo E3: 3.35 mmol/L (129.5 mg/dL)
Apo E4: 3.57 mmol/L (138.1 mg/dL)

In female drinkers the mean LDL-C was:

(These numbers are my best estimation of what is shown on the chart, since the chart reflects the average of both moderate and high intake drinkers).

Apo E2: 2.29 mmol/L (88.6 mg/dL)
Apo E3: 3.20 mmol/L (123.7 mg/dL)
Apo E4: 3.25 mmol/L (125.7 mg/dL)

We can see that:

  1. The general pattern of Apo E2 carriers having lower LDL-C compared to Apo E3 carriers, and Apo E4 carriers having higher LDL-C than Apo E3 carriers held true in both female non-drinkers AND drinkers.
  2. In all Apo E genotypes, the LDL-C was lower across the board for female drinkers, with the biggest decrease occurring in Apo E2 carriers.

Takeaways

  • Drinking alcohol is associated with a lower LDL if you are an Apo E2 male.
  • Drinking alcohol may actually raise LDL if you are an Apo E4 male.
  • Drinking alcohol correlates with lower LDL for all Apo E genotypes in females, with a greater decrease in Apo E2 females.
  • Since nearly all subjects were white, any extrapolation to non-white populations is purely speculative.

This still makes me curious to know my own Apo E status.

5 Responses to Apo-E, Alcohol, and LDL Cholesterol – The Framingham Offspring Study

  1. Michele says:

    I’d be curious to know too. Looking at it I would either be an Apo E3 or E4. I’m pretty sure drinking raises your HDL, at least Southern Comfort!

  2. Cal says:

    Interesting. I have tested and am an E2/E3. Don’t drink alcohol, and my LDL is through the roof! Maybe drinking some alcohol will lower it. Will try it and see what comes out in my next blood work.

  3. PghPammy says:

    I am E3/E3 having been eating HFLC for a year and my last two labs were each higher than the previous – Total C, LDL, and HDL. I very seldom have a drink. Special occasions and then only one. I have labs dating back to 1989 and looking over the last 10 years, including the 2000-2005 when I was on statins (quit statins 3 yrs ago), weighed 35 lbs more, was following SAD diet, and drinking/stressing lots more, the only big differences that jumps out is my greatly improved HDL and Triglycerides. Doc tried to get me back on statins and I asked for more labs – Lp-PLA 2, APO B, homocysteine, hsCRP and even doc had to admit that they look good. Total C and LDL don’t tell you the useful information, imo.

    • BJJ Caveman says:

      It looks like what’s happening to your body is the same as mine.

      I also got my Apo E checked recently. I’ll go into the results in future posts. But yeah. I’m going to definitely explore what’s happening more deeply, so stick around.

      I’m in the process of trying something different for my cholesterol, so it will be interesting to see if it works!

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