APOE 4/4 4x increase in mortality from Covid-19

[GemmaJ]

Hello Everyone,

I have just read an APOE 4/4 Info post on Facebook that included this article:

https://academic.oup.com/biomedgerontol ... 69/5867501

As a UK (European descent) APOE 4/4 teacher, I am shaken and alarmed by it and I guess I'm seeking some reassurance, if there is any to give. Over the last 3.5 years I've worked hard to 'turn off' my APOE4 gene, following the protocols suggested and discussed on this website. Do you think all the measures our community takes to prevent Alzheimer's, heart disease etc. may also give us a better chance of surviving Covid? I sincerely hope so as I'm teaching groups of students and our school policy has so far been 'no face coverings'. I'm really frightened and fed up of all the screwballs our genetic status seems to throw at us. I'm trying to stay optimistic so ANY nugget of positive wisdom would be much appreciated......

[Anna]

Ugh! Well this is horrifying I have the same questions as you and wonder what the mechanism is. My best guess is that a good chunk of this is the increased cardiovascular disease and that the statistics would look a lot better for those of us taking steps to prevent AD. I'm frightened too, especially since I have immune challenges (autoimmunity, chronically active Epstein Barr, low normal IgA) and some mild airway issues. That said, I do take comfort in having excellent numbers in terms of insulin resistance, lipid profile, nutrient status (including optimal vitamin D and zinc levels), homocysteine, etc and a recent Self Decode genetic report that shows average risk for a cytokine storm (Self Decode has a COVID risk report, but I'm sure it didn't include ApoE status). I also take comfort in having an arsenal of supplements to prevent getting super sick with COVID and to prevent a cytokine storm.

[Tincup]

I think this may have been discussed previously. Here is a search on COVID on this site.

Also, look at the absolute numbers, not relative risk. From the paper, "Similarly, of 8,767 e4e4 participants, 59 tested positive (673 per 100,000), of whom 13 later died (Table 1)" You could rewrite this as "Similarly, of 8,767 e4e4 participants, 8,708 tested negative (99,327 per 100,000). Of the original 8,767 e4e4 participants, 8,754 lived."

[GemmaJ]

"Similarly, of 8,767 e4e4 participants, 8,708 tested negative (99,327 per 100,000). Of the original 8,767 e4e4 participants, 8,754 lived."

Yes, Tincup - you are SO right. Sometimes it's just seeing things from a different perspective, isn't it. Thank you.

I'm actually impressed that they found 8,767 e4e4 participants too - Genetic testing is still not the norm here unless it's ancestry, which everyone seems much more interested in than health! So I feel less lonely walking around now, knowing that there are quite a few of us e4e4s here in the UK!

Anna - keep fighting the good fight - you're doing brilliantly by the sounds of it. Thanks to you both.

[Tincup]

If you look at Table 1 in the paper, the odds ratios are relatively constant, even excluding those with various illnesses. One thing stands out, however. When you exclude hypertension, the death rate per 100,000 is 57% of the death rate for the total group of 4/4's. Message - don't have hypertension (this drop also holds for 3/3's).

Personally, my systolic BP started to go above 120. I assume the first thing to look at as causative is hyperinsulinemia. I water fasted 5 days in March and the BP was non-responsive. So I went a different direction, one was Zona, an isometric handgrip device. The device is pricey and it may be possible to mimic its effect other ways. The protocol is to daily measure the maximum grip strength of each hand. Then you hold the right hand at 30% of that for 2 minutes, rest 1 minute, hold the left hand at 30% of its max for 2 minutes, rest one minute and then do it again the same way for each hand. Takes a minimum of 4-6 weeks to see results and a minimum of 5 days per week. See here and here. I also started training with KAATSU blood flow restriction bands. More here. My systolic BP now generally ranges between 106 and 114 (diastolic is around 60).

[GemmaJ]

Wow Tincup. Zona looks interesting and well done for your amazing results with it!

You have once again made me feel better. I've always had really low blood pressure so hopefully that will count in my favour.

Thanks again for your reassurance.

[TH23]

I just got on here for this subject and I'm amazed there's only 5 comments! Is this a big deal or not?

I'm 48 4/4 and mthfr 4/4. What's the good news about being apoe4/4?

[Tincup]

I'm 48 4/4 and mthfr 4/4. What's the good news about being apoe4/4?

Not sure most consider it being good news. For more details about being ApoE4/4, see our Primer.

In this post, the paper shows a dramatically lower risk for CVD for those who are ApoE4 positive and don't have metabolic syndrome. My own view is that the ApoE4 risks are from a mismatch of a lifestyle of excess with an allele that excels at inflammation (good in an acute setting, bad in a chronic setting) and surviving deprivation. My 4/4 wife and I are patients of Dr. Steven Gundry. We've posted redacted labs and transcripts of 9 hour long consults with him here. In the included notes to Gundry, we've included what we do.

[NF52]

I just got on here for this subject and I'm amazed there's only 5 comments! Is this a big deal or not?

I'm 48 4/4 and mthfr 4/4. What's the good news about being apoe4/4?

Welcome, TH23, from another ApoE 4/4 who is 20 years older than you and still going strong! To try to give a balanced view, the risk of COVID is probably a big deal to almost everyone on this site, especially when the news suggests that we might be at a bigger risk of dying from it! But with the virus so new and the testing so limited in some areas (including the UK in March and April when this data was collected), there a lots of what researchers call "limitations on the results of this study"--factors that may explain the results differently. Here are just some:

1. In the UK, it appears that testing was only done on people who arrived at a hospital. Recent data from "prevalence testing", which is like sampling a given population regardless of symptoms, suggests that about 40% of people with COVID-19 are asymptomatic.
2. Of the ApoE4/4 people tested, not quite one percent tested positive. That means that in a group of 300 people with ApoE4/4, 298 would not have the disease. That's a lot of healthy ApoE 4/4s.
3. Of the 59 symptomatic people with ApoE 4/4 who had (probably severe) disease, 13 died. However, this was in the months when doctors were learning quickly to monitor blood oxygen levels early, use medications for people with heart disease to reduce risk of strokes or blood clots, and use remdesivir for treatment. We don't know if these people would have had different outcomes today.
4. The people in this study had been followed for years, but it appears that any diagnosis of dementia had not been updated since 2017. I know from my own relatives that someone who looked healthy at age 80 could be very frail at age 83.

Of course, we don't know why some younger, healthy people have severe disease, so the advice for all of us remains true: wear a mask in enclosed spaces, use social distancing to reduce your risk and wash your hands frequently.

As for the good news about being ApoE4/4, I'll admit that when I first found out it didn't seem like good news. But it led me to make better choices for prioritizing sleep, fewer carbs, more exercise, meaningful social and cognitive challenges and recognizing that each day is important. In my own extended family with a history of cognitive impairment, there is no breast cancer, no melanoma (in spite of ghostly pale skin), and few other serious diseases. Most women live into their 80's, a good 40 years past when my grandparents lived in a time of poor control of heart risk and use of carcinogens in smoked foods. And going way back, it appears that ApoE 4/4 protected against deadly disease like malaria and parasite diseases in hot climates and against starvation in periods of fasting in cold climates. There's even some studies that suggest we have higher than average verbal intelligence and executive functions (planning, organizing, problem-solving), which will help us navigate a path through a gene that only signals a risk--it doesn't control the steering.

We're glad you found this community and hope you will tell us more about how you're coping with the dual challenges of ApoE 4/4 and COVID-19. Hugs from a genetic "relative"!

[MicheleCC]

I just got on here for this subject and I'm amazed there's only 5 comments! Is this a big deal or not?

I'm 48 4/4 and mthfr 4/4. What's the good news about being apoe4/4?

Hello TH23! Glad to have you join the conversation here on apoe4.info. You've already been welcomed by two of the most well-informed members of this site that I know of, so as an intern on the site, I'd like to welcome you as a new member and point you to a few areas you may find useful.

Primer
As Tincup pointed out, the Primer is a good place to learn more about the possible implications of having the apoe4 gene.

How to get the most of the apoe4.info website
As a new user, you may find the "How-to" section of our Wiki useful in learning the ins and outs of navigating and communicating with others on the site.

Our Stories
A major feature of this site is that we learn from and support one another. We enjoy getting to know fellow users and invite you to share your story on the "Our Stories" thread.

Within the Functional Medicine community, it's believed that at least 75% of genetic expression is under the direct influence of environmental factors, meaning it's largely under your control. Self care is the best care. We hope you'll find the apoe4.info community is one that supports you in your efforts to be optimally healthy--during a pandemic or anytime!

Warm regards,
MicheleCC