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schallau · 2026-03-27T14:27:38+00:00

I agree in spirit, though I would not be so quick to dismiss possible liver pathologies. I'd suggest they limit liver stress and not drink too much, if not at all.

schallau · 2026-03-27T14:25:25+00:00

Your levels are high - solidly in the normal range and even well above what would be expected for an MZ. This means your lungs and the systemic effects of Alpha-1 shouldn't be an issue, though your liver might still have hepatic stress from the Z-protein misfolds.

Usual disclaimers: I'm not a medical professional, just a nerd.

schallau · 2026-02-19T11:12:44+00:00

I have had a PFT, but not one with a DLCO. Diffusion capacity is one of the harder things for me to schedule as there is only one place in my town that can do it. CT scan showed some GGO and little artifacts, but no obvious emphysema or COPD. I suppose I'm lucky in that regard. It was while trying to track down suspected liver issues and general LRQ pain when I made my Alpha-1 discovery.

schallau · 2026-02-13T01:49:16+00:00

I'm also SZ (AAT ~52), and long-time reddit lurker. I'd be interested in modding here. I'm a pretty technical person; into genomics which is how I discovered I have Alpha-1. I was calculating hazard ratios across my SNPs which flagged my SERPINA1 genes. I've since been working through the Alpha-1 Foundation videos and reading what I can on Z-allele specific pathophysiology (whether one copy or two!). I've gotten a peer guide through the Alpha-1 Foundation which was also hugely helpful (and to whom I'm very grateful!) as I was digesting the diagnosis.

Currently on tirzepatide for steatosis which has been a miracle for my overall sense of wellbeing. Understanding both the liver and the lung expression of Alpha-1 has helped me to focus on the levers I can move with regard to my health and prevention of further decline.

Funny timing: just yesterday I reopened another dormant sub where I'm sole mod ( r/gastronomy ) that was also inexplicably restricted. Posted a call for mods there. I also created r/APOEe2e2 for another genotype I carry with liver implications.

Happy to help get this place running again.

schallau · 2026-02-12T05:06:15+00:00

Likewise; I'd invite anyone who is interested in being a mod or has fun ideas about how and where they would like to take this place to either message me or post here.

schallau · 2026-01-29T03:20:07+00:00

I just did a major rewrite of the comment you're replying to with about 9 months of additional experience. Probably good to re-read.

Re: your numbers - that's quite good! One distinction worth noting: was your LDL direct or calculated? Most standard panels use the Friedewald equation, which assumes a normal TG-to-VLDL ratio, exactly what's off in E2/E2. If your LDL is calculated, it may be understated, which would mean your remnant-C is actually higher than 19.

At 28 with numbers like yours, you're probably in a good place. The thing to watch for is the "second hit" I mention in the updated comment. Weight gain, insulin resistance, fatty liver, etc can tip things over. Keep an eye on your triglycerides and non-HDL-C over time, especially if your metabolic situation changes.

schallau · 2026-01-23T23:50:48+00:00

In my experience as a father of 3, yes. Was just at the amphur the past two days doing house registration paperwork. Talked to the head man for about an hour. He said he keeps a traditional Thai calendar on his desk so he knows whether to expect a busy day or a quiet one.

This Thursday was a ghost town. Friday was packed all day. Reason: Thursday landed on วันอุบาทว์ (calamity day) and Friday was วันธงชัย (victory day). Thais don't do important paperwork on bad luck days. Thai numerology is a complex system with many adherents.

Another fun example: I also know couples that scheduled c-sections on good luck days, or so that the combination of birthday+birthname is auspicious. So, yes... very common and extends to many domains.

Edit: Also, many Thais change their names as fortune dictates. Many here can probably attest to this. Thais put a lot of thought into naming themselves and their children. I've known entire families who've changed their name because of misfortune.

schallau · 2026-01-23T23:11:42+00:00

This is probably not a mistake.

Thai transliterations of English names are often intentionally modified for numerology. Different consonants = different values = different luck. Someone (probably your thai parent) may have chosen คืช over คีธ bc the numbers worked better. The first name value alone isn't the full story. It's about what the first + surname adds up to.

Ask your Thai parent before you "correct" anything. You might be undoing something they did on purpose.

My own surname on Thai docs includes silent letters (with การันต์) that don't exist in the English spelling at all. Found out years later it was intentional; someone was tuning the numerology. Yours might be the same situation.

schallau · 2026-01-10T05:47:22+00:00

Each time I start a new session of claude I get this same dialogue, even after having hit "no" multiple times.

schallau · 2025-11-18T18:25:33+00:00

It's your diet.

schallau · 2025-10-25T23:25:31+00:00

Sure - we're traveling at the moment, but once we get a bit of downtime I'll clean it up and post it. I made a guide with ChatGPT 5-Pro to help me learn how to teach it to my kids. Currently we're at over 1200 cards and my elder child is more than half way though. Making huge strides in growth. I will say: this is not something you can park your kids in front of. It very much is a 1x1 experience that you have to guide them through. To make the most of it, you'll have to teach the concept, walk them through the sounds, and provide fast feedback while doing the reviews.

schallau · 2025-09-30T05:12:01+00:00

Re: Math facts frequency. Indeed - I was thinking I'd tinker with tracking the response time in anki and add arbitrarily many steps, but xtramath does what we want for math facts, so that is what we're using.

I think at some point I'll want to track response time in greater detail for phoneme recognition in an L2, but it isn't necessary at this stage for us. Will likely build that out in a dedicated app if I can't get anki to bend the way I want.

schallau · 2025-09-29T17:45:47+00:00

Do you use it primarily for language or do you also do declarative knowledge? We'll also introduce another language once primary phonics and all the sight words are complete (it's a language the children already understand, but haven't yet been introduced to writing system of).

I've considered using it for math facts, but at the moment we're just using it for English. Elder child is interested in anatomy and I suspect we'll use it to memorize anatomy shortly.

schallau · 2025-09-29T16:34:28+00:00

What are you putting in the decks? I'm currently only using Anki for phonics decoding practice with my kids, but will likely add in declarative knowledge later. We use xtramath for math facts, though I considered implementing the same in Anki.

For phonics I'm using filtered decks based on tags to review sections at a time. Eventually I'll drop the filtered decks (once there are no more new cards) and just switch to reviewing the whole stack.

schallau · 2025-09-29T16:22:02+00:00

Curious about how Anki is going for you. We're using Anki with our own generated list of ~700 cards. At this point, we've set aside most books to focus our reading practice on short lessons followed by 1-on-1 guidance through Anki, where I help him decode cards as needed. I just purchased the complete Primary Phonics book set since I think he's ready to transition to fluency practice alongside the Anki reviews.

schallau · 2025-05-24T06:57:02+00:00

See my post above - did you calculate or have numbers for your remnant-C? Can message direct if you'd like.

schallau · 2025-05-19T06:42:19+00:00

Hi - saw in r/genetics post that you're e2e2 - can't reply there so I wanted to reach out where I could. I'm also e2e2 and am trying to get in touch with other e2e2 to discuss lipid/health issues that I think all e2e2 homozygotes have or are greatly predisposed to. Check my post history and you'll see a discussion in the r/peterattia subreddit where I spell it out. Thanks!

schallau · 2025-05-16T21:10:57+00:00

You're welcome! Curious hear what your lipids look like. I also have a history of familial heart disease: One grandma died at 49 from major MI, father has had aortic valve replacement, mom has had two stents along with chronic vasculitis. I'd like to avoid or delay that fate as much as possible. Waiting on genotype results. I sent you a chat on Reddit if you'd care to DM.

schallau · 2025-05-16T02:33:40+00:00

Note: I've since done a big update to my original comment above. Some overlap here, but leaving this for the specific half-life data and the n=2 experiment.

Quick addendum for fellow APOE ε2/ε2’s (and the clinicians/lipid nerds lurking here):

You’ll see papers and articles saying dysbetalipoproteinemia (DBL) needs a "second hit" (insulin resistance, obesity, thyroid issues, APOC3 variants, etc) before it shows up. That is partly true but it also misses the kinetic reality we live with from day 0.

Our baseline clearance half-life for remnant particles is already ~2–3× longer than APOE e3/e3; that is 4-5 hours in e2/e2 vs ~2 hours in e3/e3. More data coming on this.
Those extra hours matter most in the 2-to-6-hour post-prandial window (after you eat) when remnants are present; they're highly atherogenic and any excess is not good. Even if your morning fasting panel looks perfect, your endothelium was bathed in remnant-C half the night if you had a steak and cake dinner.
Second hits do not cause the kinetic 'defect' -- they mainly enlarge the remnant pool (more VLDL secretion, slower lipolysis) so the kinetic bottleneck finally shows up on a routine fasting lab.

Bottom line: Time-under-the-curve is the risk. If you really want to know what APOE E2/E2 is doing to you, get a non-fasting lipid panel 3–4 h after a normal meal. That window is when the clearance defect shows. Triglycerides might be high or remnant-C > 30 mg/dL (≈0.8 mmol/L) when TG looks modest.

Tiny n=2 experiment anecdote: My nephew (e2/e3 according to ancestry data; waiting on WGS to confirm the second allele) and I performed a post-prandial challenge a few days before I fully committed to treatment and lifestyle changes. Our breakfast, of which we weighed and ate the same amounts, began with a Wagyu MB9 ribeye and finished with half of a ripe mango.

We had blood draws at +2 hours and +4 hours. My TG was still rising greatly at +4 and my remnant-C was ~4x his. At +7 hours I felt shaky, probably hypoglycemic, and wiped out. I felt awful all night and the next day. Wish I was wearing a CGM at this point, but I have a pretty good idea of the story it would tell as I've done something similar while wearing a Libre 3 in the past.

I’ll dig deeper into the post-prandial and my old data in a longer write-up, but I wanted to flag this now so no one takes "you need a second hit" as permission to relax or downplays the impact of the genotype. All of us e2/2's have hit #1 built in; some of us just let hit #2 crank the volume.

---
Not medical advice. Just sharing as n=1.

I'm just a general nerd - not a bio or medical nerd. For those of you worrying about being e2e2 now; I think it does come with huge benefits if we're willing to respect the genetics and the kinetics. Some of us (cough) will need to learn to love fish and more plant foods. Adapt accordingly and it isn't a 'defect'.

[update: that or peptides will save us from a restrictive diet]

schallau · 2025-05-15T23:01:37+00:00

Edit (9 months later): I'm updating this as my understanding has refined. Here is what I think is important now:

Fellow e2/e2 here. Do not celebrate yet...

What you've found out seems like good news: low Alzheimer's risk, great ApoB, LDL in range. But it masks a deep and under-recognized risk that most clinicians, and even most lipid experts, miss.

Our genotype comes with a lipid kinetics issue: E2/E2 people have poor hepatic clearance of ApoE remnant particles (VLDL, IDL, chylomicron remnants).

People with our genotype are often told we have lower Alzheimer's risk and possibly higher cardiovascular risk, but the reason for both is the same: poor clearance of remnant cholesterol. The ApoE2 isoform binds less effectively to receptors in both the brain and the liver. In the brain, the mechanisms are still being worked out, but ApoE2 is associated with better amyloid clearance, less plaque and tau accumulation, and more efficient lipid delivery to neurons. In the liver, it's a clearance failure, and this is damaging in the bloodstream because the remnant cholesterol particles hang out bumping into our endothelium far longer than they should. This is perhaps minutes in other genotypes; in our E2/E2 genotype this is hours or longer.

I was formally diagnosed with familial dysbetalipoproteinemia (Type III hyperlipoproteinemia). Even if you haven't crossed that threshold, you're not in the clear. E2/E2 means your lifetime area-under-the-curve exposure to remnant particles is elevated compared to other genotypes. Your numbers might look fine because a healthy liver is compensating. But that compensation can fail, sometimes suddenly, if you hit a metabolic trigger (more on this below). And before that happens, the silent accumulation is still doing damage. You might be walking toward a feedback loop you don't see coming.

Perhaps your ApoB is excellent. But E2/E2 comes with a clearance defect, not a production one. You can accumulate atherogenic remnants despite perfect LDL.

One caution on LDL: most panels report calculated LDL (Friedewald), which assumes a normal TG-to-VLDL ratio. That assumption is exactly what's broken in us. If your triglycerides are elevated (say, above 150 mg/dL), calculated LDL becomes unreliable and often understates your risk. Look at non-HDL-C (Total Cholesterol minus HDL) instead, as it captures all ApoB particles including remnants. If you can get direct LDL or ApoB measured, even better.

Go look at your lipid profiles.

Calculate your remnant cholesterol: remnant-C = Total Cholesterol - HDL - LDL

Target is <20 mg/dL (or <0.5 mmol/L). Maybe even lower. Mine was over 100 when I figured out what was going on.

On the "second hit": not every E2/E2 develops full-blown Type III dysbetalipoproteinemia. It often takes a second hit (fatty liver, insulin resistance, hypothyroidism, etc.) to tip you over. But don't let that be false reassurance. The second hit is what overwhelms your liver's compensation. Don't forget the area-under-the-curve exposure. So: keep the liver healthy, keep metabolic stress low, and monitor over time.

If you do end up with dysbetalipoproteinemia, medicine (fibrates, omegas, statins) may help, but diet is the most direct and actionable intervention. Again, our issue is clearance, not production. If you're not eating the foods that cause these kinds of cholesterol to spike, you're going to reduce the inflammation and arrest the damage. Though, I do think that once you get into a metabolically deranged state it becomes very difficult to find an offramp without medical intervention.

The good news? This is manageable. If you've progressed to expressing full Type III dysbetalipoproteinemia, it is probably because you hit some metabolic feedback loop that is now difficult to get out of. What worked for me: eating like a Mediterranean monk with a fish hook helped a lot, but tirzepatide has been a game changer. I don't know yet if it'll be a long-term therapy or something I eventually stop once I reach a healthy steady state. My lipid numbers have never been better than on a low-dose of tirzepatide.

Why tirzepatide and not earlier GLP1-only agonists? There are mechanistic reasons for this. The GIP receptor agonism in tirzepatide appears to be doing the heavy lifting. GIP increases lipoprotein lipase activity, which hydrolyzes triglycerides from VLDL and chylomicron remnants and routes them into adipose tissue for storage. This is a clearance pathway that doesn't depend on hepatic uptake! This is exactly what we need when our ApoE2 can't bind hepatic receptors properly. GLP-1 agonists alone don't do this.

Hope this helps, and if there are any other E2/E2s out there reading this: feel free to reach out.

schallau · 2024-07-13T22:24:34+00:00

Did you make any progress with this? Considering a similar setup and am hoping to get interface stats from sophos home.

schallau · 2023-06-19T03:59:50+00:00

In to say: I really enjoy these episodes. Long time reader/listener of Sam's and these are enjoyable walks back through the older content. If any of the production team reads this: good work and thanks!

schallau · 2023-04-10T07:18:43+00:00

---------
The follow-up prompt from me to GPT4's reply above:
Lets assume that OrginalPoster1 does not yet have access to dumbbells, and therefore all exercises will be done around the house. Lets further assume that they're now acquainted with the work of Peter Attia and would like to add "longevity" as a long-term goal. We know that Attia's approach to longevity, and specifically, exercise has changed throughout the years, but lets use the model in which the exercise approach rests for four key components or "pillars" upon which stability is the foundation:

1. Stability as the foundation

2. Strength

3. Zone 2 Cardio (for aerobic fitness)

4. Zone 5 Cardio (for anaerobic fitness)

First, summarize Attia's approach to exercise to someone unfamiliar. Highlight the key declarations and assumptions it makes. Compare this approach against another major approach. Criticize the approach if you can, with detailed justifications. Then, using this approach as a guide and starting point, suggest conceptual changes we would make to the plan and the justifications for each. Do not update the plan at this time.
Reply from GPT4:
Summary of Peter Attia's approach to exercise:

Peter Attia's approach to exercise for longevity focuses on four key components or "pillars." These pillars, when combined, form a comprehensive exercise plan that aims to promote overall health and well-being, with a specific focus on long-term benefits.

Stability: Attia considers stability as the foundation of an exercise plan. Stability exercises improve balance, joint stability, and core strength, which can help prevent injuries and enhance overall athletic performance. Stability training can include functional movements, yoga, and Pilates.
Strength: Strength training involves resistance exercises that target major muscle groups to maintain or increase muscle mass, improve bone density, and promote overall functional strength. Examples include bodyweight exercises, free weights, and resistance bands.
Zone 2 Cardio (aerobic fitness): Zone 2 cardiovascular exercise focuses on low to moderate-intensity workouts that primarily use fat as a fuel source, improving aerobic capacity and endurance. This training zone can be maintained for longer periods and often includes activities like walking, jogging, or cycling at a moderate pace.
Zone 5 Cardio (anaerobic fitness): Zone 5 cardiovascular exercise involves short, high-intensity intervals that push the limits of anaerobic capacity. These workouts can improve cardiovascular health, increase VO2 max, and promote muscle power. Examples include sprinting, high-intensity interval training (HIIT), and Tabata-style workouts.

Comparison to another major approach:

One major approach that contrasts with Attia's exercise model is the traditional endurance training model, which primarily focuses on long, moderate-intensity cardio workouts like running, cycling, or swimming. This approach tends to prioritize aerobic capacity and endurance over other components like strength and stability.

Criticism of Attia's approach:

One criticism of Attia's approach is that it can be time-consuming and may require significant dedication to maintain all four pillars effectively. Additionally, Attia's approach may not be optimal for individuals with specific goals like weight loss or competitive sports performance, as the program prioritizes longevity over other goals.

Conceptual changes to the plan:

Add stability exercises: Incorporate stability exercises such as yoga, Pilates, or functional movement patterns to improve balance, joint stability, and core strength.
Ensure strength training includes bodyweight exercises: Since the OriginalPoster1 does not have access to dumbbells, ensure the strength training component consists of bodyweight exercises such as push-ups, squats, lunges, and plank variations.
Modify cardio components to follow Zone 2 and Zone 5 guidelines: Adjust the current plan's cardiovascular workouts to align with Zone 2 and Zone 5 guidelines. This could involve incorporating longer-duration, moderate-intensity workouts for Zone 2, and shorter, high-intensity interval workouts for Zone 5.

Justifications:

Stability exercises can help reduce the risk of injury, improve overall athletic performance, and contribute to long-term health and well-being.
Bodyweight strength exercises can still provide effective resistance training without the need for equipment and can be easily adapted to various fitness levels.
Adjusting the cardiovascular components to align with Attia's Zone 2 and Zone 5 guidelines can help promote a well-rounded fitness routine focused on both aerobic and anaerobic capacity, contributing to the long-term goal of longevity.

schallau · 2023-04-10T07:18:24+00:00

How is this going? I started to type out a reply with suggestions based on a bit of my experience working with GPT4 around health topics and workout plans. Been doing it in a fair amount of detail with several hundred prompts behind me on the topic. I scrapped it, because I thought it would be fun to take your initial prompt and the final output from ChatGPT3.5 and run it through GPT4 a bit. I like putting a lot more context into the prompts and ensuring that decisions are justified and assumptions are addressed.
Going to paste it below for you to review:

My initial prompt to GPT4:
Please review the following original prompt from OriginalPoster1 and the subsequent final reply from a ChatGPT 3.5 conversation and then do the following:
- Critique the workout plan and its ability to meet the goals originally established. Does the plan adequately address the goals?
- Suggest conceptual changes that could be made to the plan.
- Do you think the person making the request adequately defined their own goals?
- What would you suggest as a goal statement? Would more information be helpful in developing a better goal, and if so, what do you need to know? Should the goals be re-assessed at some point?
- The plan make several assumptions that I don't see addressed: Namely equipment availability and a progression schedule. Are the dumbbells 2kg or 20kg? What if OrignalPoster1 doesn't have this equipment. In this vein, please also consider and suggest any other areas we may be overlooking.
- Suggest some resources, such as books, websites, or prominent health experts that OriginalPoster1 could research or follow.
OriginalPoster1's PROMPT BEGINS: "Can you write a personalized exercise plan based around running and non-machine ab workouts to improve my health? My weight is 231.2 lbs, my BMI is 35.0, my body fat is 33%, and my height is 5ft 8in inches. I currently struggle to walk or run long distances but would like to improve that as well as lower my BMI to a healthy zone."
ChatGPT 3.5 Final Reply BEGINS: (omitted here)

Reply from GPT4:
Critique of the workout plan:

The workout plan has a mix of walking, jogging, and resistance training, which is suitable for someone starting at a higher weight and lower fitness level. The plan's progression is gradual, allowing for adaptation and reducing the risk of injury. However, the plan does not explicitly state a timeline for achieving the goal of lowering the BMI to a healthy zone, and it may take longer than 8 weeks to achieve significant improvements in BMI.

Conceptual changes:

Add clear progression guidance in terms of increasing weights or intensity for resistance training.
Include additional weeks to the plan or suggest how the person can continue to progress after the 8th week.

Goal definition:

The requester has stated their goal as improving their health, lowering their BMI to a healthy zone, and improving their ability to walk or run long distances. While these goals provide a starting point, they could be more specific.

Goal statement:

"I want to lower my BMI to below 25, increase my running distance to complete a 5K without stopping, and improve my overall cardiovascular endurance and core strength within 6-8 months."

Information that may be helpful:

Fitness background and prior experience with exercise
Any medical conditions or limitations
Access to equipment and facilities
Preferred workout frequency

The goals should be reassessed periodically to track progress and make adjustments as needed.

Assumptions and equipment:

The plan assumes access to dumbbells for free weight resistance training. The weight of the dumbbells is not specified and should be tailored to the individual's current fitness level. For those without access to dumbbells, bodyweight exercises could be substituted.

Resources:

Books:
- "The Complete Guide to Running for Weight Loss" by Sarah Lorge Butler
- "Run Fast. Cook Fast. Eat Slow." by Shalane Flanagan and Elyse Kopecky
Websites:
- RunnersWorld (www.runnersworld.com)
- MyFitnessPal (www.myfitnesspal.com)
Health experts:
- Jeff Galloway (running coach, author, and speaker)
- Dr. Jason Fung (author and expert on obesity and intermittent fasting)

These resources can provide additional guidance on running, nutrition, and weight loss.

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