What APOE4 carriers talked about in October

Phoenix is growing faster than ever. More than 750 APOE4 carriers now bring their questions, blood work and daily check-ins to one place, so nobody has to figure out APOE4 alone.

Here's what they talked about in October, what we published for free, and two dates that matter if you've been thinking about joining:

• Friday 6 November: this month's pods close. Join by then and you're matched into a small group of carriers this month with similar goals.

• Sunday 8 November: the last day for members to send their questions to Dr. Michael Davidson, CEO of NewAmsterdam Pharma, the company behind obicetrapib.

What carriers talked about most

• Deep sleep, and how to actually get more of it. The busiest conversation of the month. What carriers said helped them: strength training, morning light, a cooler room, brown or pink noise, and no caffeine. The surprise: two wearables can disagree a lot on the same night, so most watch their own trend, not one night's score.

• Cutting back on supplements. Many have trimmed their stack to the few things their own blood work supports, and swapped notes on what to retest after cutting.

• Fibre without glucose spikes. Real glucose-monitor data: the same lentils spike one person and not another, and a perfectly flat line isn't the goal.

• The new Alzheimer's drugs, from the inside. A member's year on donanemab, and others comparing notes on screening for a prevention trial.

• Small blood vessels and the brain. Blood pressure (including at night), waist size and sleep apnea, and why they matter for carriers.

That's the difference between Googling alone at midnight and comparing notes with 750+ people who carry the same gene.

Every other topic and the insights since mid-September is at the bottom of this email.

Free to watch and read

• Dr. Gayatri Devi: two copies of APOE4, what should you do next? Get a full memory baseline, then retest about once a year unless something changes. Watch

• Dr. Grant Fraser: your p-tau went up. Is your brain getting worse? Look at the trend, not one result, and repeat the test the same way. Watch

• Dr. Ashanthi Gajaweera on menopause and HRT: Part 1: have you missed the HRT window? and Part 2: when your doctors disagree.

• Just out: Dr. Jessica Langbaum, should you join a prevention trial? Watch

• My own story: Two copies of APOE4: the result that changed my life.

• Five short explainers to send to family: Can carriers eat eggs? · Is APOE4 inherited? · How common is APOE4? · APOE2 vs 3 vs 4 · How does APOE4 cause Alzheimer's?

October's APOE4 news

• A cholesterol drug enters an Alzheimer's prevention trial. NewAmsterdam started SPINOZA, testing obicetrapib in about 400 people with early blood-marker changes and no symptoms, including carriers. The trial

• Genes that may protect carriers. A large genetics study found 42 regions of DNA that may soften APOE4's risk. Early science, no treatment yet. Read

• APOE4 and the brain's insulation. MIT showed how APOE4 disrupts the cells that insulate nerve fibres. Shown in mice and lab-grown tissue only. Read

• APOE4 and small blood vessels. Mount Sinai showed APOE4 pushes the support cells around brain vessels toward scarring. Reversed in mice, not yet in people. Read

Coming up: seven experts, and members ask the questions

Members send their questions in the community, and I ask the top ones on the recording.

• Dr. Dale Bredesen: what to do, track and trust. Out next week.

• Dr. Michael Davidson, CEO of NewAmsterdam Pharma: can a cholesterol drug matter for an APOE4 brain? Questions close Sunday 8 Nov.

• Dr. Aubrey de Grey, LEV Foundation: can repairing aging protect the APOE4 brain? Questions close 15 Nov.

• Dr. Fatemeh Ramezani, Cedars-Sinai: the MIND diet, your gut and APOE4. Questions close 15 Nov.

• Sarah Fontaine, PhD, Alzheimer's Association: what the U.S. POINTER study means for carriers.

• Jodi Scott, co-founder of Green Goo: stress and everyday exposures.

• Dr. Ken Langa, University of Michigan: why dementia rates are falling.

Join this week and your question can still reach Dr. Davidson, Dr. de Grey and Dr. Ramezani.

Pods are open until this Friday

You don't have to do this alone. Every month, members are matched into a pod: a small group of APOE4 carriers with similar monthly goals.

This month's pods stay open until Friday 6 November, end of day Pacific. Join Phoenix by then, request your pod in two minutes, and you're matched on Saturday 7 November.

What members get

• Your next step, always clear: a personal APOE4 roadmap, your blood work read against APOE4 targets, and experiments that show whether what you take is working.

• Everything in one place: the new Phoenix app on iPhone and Android, with Apple Health, Oura, Garmin and more syncing in the background.

• People who get it: monthly pods, expert Q&As all year, and 750+ carriers comparing notes.

• Member prices: blood tests up to 70% below retail (US for now), and supplements up to 35% off in the US and up to 25% off in Canada.

Phoenix takes no commission on anything it recommends to members. Any commission we could take is directly passed to you as a bigger discount. If we recommend something, it's because we believe it can help you. You buying it never earns Phoenix a cent.

Phoenix is fundraising to grow faster and serve you better!

I've built Phoenix solo until now, and we're growing faster than ever: 750+ APOE4 carriers and counting. Now we're raising our next round, so we can hire and build faster. If you’d like to join me in this adventure, reply to this email and I'll share the details privately. Not an investor but want to help, with an intro, an idea or a skill? Reply too. I read every one.

Not a part of Phoenix yet?

Stand on the shoulders of other APOE4 carriers. Join by Friday and you're in this month's pods.

Apply to join Phoenix

And if it's not for you, there's a 60-day money-back guarantee.

Cheers,
Kevin

P.S. Everything carriers talked about since mid-September

And here's everything else carriers discussed in the community from mid-September to today, grouped by theme. Members can join any of these threads.

Sleep

Deep sleep: how to get more of it

• The busiest thread of the period: members who already follow sleep hygiene compared what actually raised their deep sleep.

• Strength training, morning light, a cool room, brown noise and no caffeine came up most; glycine, inositol, tart cherry and orexin sleep drugs were debated.

• Many found their wearable was the problem: different devices showed very different deep sleep, so members agreed to watch trends on one device, not single nights.

Melatonin: does a low dose help, and is long-term use safe?

• Continued from September: members asked whether a very low dose could disrupt the body's own melatonin over time.

• Several stressed morning daylight or a light-therapy lamp and dim, warm light at night; a few said higher doses left them groggy or waking early.

• Some noted research linking APOE4 to lower melatonin and wished for a proper trial, which is unlikely since melatonin cannot be patented.

Orexin sleep drugs: do they lose their effect?

• Members on the newer orexin-blocking sleep drugs (Quviviq, Dayvigo) said the effect faded a little after the first weeks but still helped.

• Members discussed how to keep them working over time, and agreed any change is one to make with their doctor.

• A few also noticed better sleep after changing or restarting a bedtime cholesterol drug, and wondered whether that is a real effect.

Older sleep threads picked up again

• Older threads on inositol, glycine and magnesium, phospholipid fish oil and early-morning waking got fresh replies as the deep sleep thread grew.

• Members swapped timing questions (morning or night) and said how stressful it feels to need so many steps just to sleep.

• Some found they slept better when traveling, and wondered what in their home routine or diet was getting in the way.

Supplements and stacks

Cutting back on supplements

• A strong wave of members said they had trimmed their stacks because of cost, little felt difference and plain supplement fatigue.

• Several kept only what their own blood tests supported, such as TMG or B vitamins for homocysteine; a side-thread argued proven cholesterol drugs beat many supplements.

• A few warned homocysteine rose after dropping B vitamins; members asked for a ranking of supplements by strength of evidence.

Lithium orotate: benefits and side effects

• Members compared low-dose lithium experiences: some felt nothing or a lift in mood, others reported possible thyroid changes, flatness or ear symptoms.

• Common ground: check thyroid labs and drug interactions, and remember drinking water and some multivitamins already contain lithium.

• Members admitted they could not tell whether symptoms were really caused by the lithium.

Fibronectin and protecting the blood-brain barrier

• A shared article argued APOE4 carriers make more fibronectin, which may weaken the blood-brain barrier, and listed supplements that might help.

• Members noticed they already take several of them; nattokinase and serrapeptase came up as ones to look into.

• Supplement fatigue came up again, balanced against a willingness to try anything that might help.

Phospholipid omega-3s and PC supplements

• Continued from earlier: members asked why fish DHA seems so useful if phospholipid forms are broken down in the gut anyway.

• One reply raised checking TMAO when taking phosphatidylcholine supplements, since some brands may raise it more than others.

A new study questions NR and NMN supplements

• A shared article summarized recent disappointing trial results for the NAD boosters NR and NMN.

• Members noted how often supplements thought to be helpful turn out not to be, and the reverse.

New Alzheimer's drugs and trials

Donanemab (Kisunla): what treatment is like

• The most-liked member post of October sparked a wider talk about choosing between lecanemab and donanemab, for themselves or a parent.

• Practical tips: keep scans and infusions at one site, ask for a scan that gives a number, and know most side-effect risk is early in treatment.

• Left open: whether people with existing microbleeds can be treated, and whether starting a drug now rules out later prevention trials.

PrevenTron (trontinemab) prevention trial

• Members in several countries compared the screening steps: a memory test, then a pass or fail blood test, with results in about two weeks.

• The cut-off is set high on purpose, so most people screened do not qualify.

• Feelings were mixed: some hoped not to qualify since that means higher risk, others valued the close monitoring.

NeuroEPO (NeuralCIM), the nasal drug available in Cuba

• Members discussed a nasal drug for mild to moderate Alzheimer's that is only available by traveling to Cuba.

• Some found the published Cuban trial encouraging; others noted it was small, and a Canadian trial will not report for several years.

• Travel difficulty and high cost were the main barriers raised.

Obicetrapib and APOE4

• A popular podcast on obicetrapib, a cholesterol (CETP) drug with promising Alzheimer's blood-marker results, prompted questions about trials for carriers.

• Members debated a claim that nearly all 4/4 carriers develop Alzheimer's: several said it confuses brain changes with symptoms, and lifetime risk is far lower.

• I shared that I'm in touch with the drug maker about a Q&A and trial enrollment; the type 2 diabetes question was also raised.

SPINOZA: the new obicetrapib Alzheimer's prevention trial

• Members shared news that the drug maker dosed the first person in a Phase 2b Alzheimer's trial, plus the online eligibility checker.

• Several applied at one or more sites; a portal for Canada was expected.

• A blood p-tau217 cut-off is part of eligibility, so recent test timing matters.

How NeuroEPO access works, and a look-alike peptide

• A shared clinic letter laid out the process: a video assessment, approval for mild to moderate decline only, then travel to collect the drug.

• One member argued an inexpensive research peptide works in a similar way; others pointed out it has far less testing.

Arrowhead's tau-lowering drug (ARO-MAPT)

• Early results showed an injected drug crossed the blood-brain barrier and sharply cut tau in spinal fluid, with mild side effects.

• Members noted these results were in healthy volunteers; trials in people with early Alzheimer's are underway.

USC Gene Screen research registry

• A member recommended a Southern California registry that matches volunteers to brain health studies led by Dr. Hussein Yassine.

• Others asked whether it covers their area and how often participants have to visit in person.

ALZ-801 (valiltramiprosate) heads to a new trial

• Continued from earlier: members welcomed news that the drug maker raised funds for a new Phase 3 trial in mild cognitive impairment.

Expert Q&A: what members asked

Dr. Dale Bredesen: do, track and trust

• The most-liked question: how to square his mildly ketogenic plan with the Mediterranean and MIND diets most prevention doctors recommend.

• Other questions: GLP-1 drugs for prevention, protein targets, MCT oil, fish oil, copper-to-zinc ratio, p-tau217 without symptoms, hs-CRP, statins and sleep drugs.

• Several noted strict keto raised their LDL or caused too much weight loss, and asked whether one copy and two copies respond differently.

Dr. Heather Sandison: what do you change first?

• The most-liked question: which efforts, like avoiding household toxins, can be relaxed if diet, exercise, sleep and social life are in place.

• Others asked about Mediterranean keto for prevention, cholesterol on keto for people whose LDL soars, ketone drinks, hormone therapy and intense exercise for women.

• Members also asked how to help a distant parent with memory decline, how much light drinking matters, and about cosmetic treatments.

Dr. Michael Davidson: can a cholesterol drug matter for an APOE4 brain?

• Members screening for obicetrapib trials asked about age limits, stopping current cholesterol drugs, keeping access after a trial, and when it could reach the US.

• Others asked whether it helps people whose LDL is already low or HDL already high, and how much a small 4/4 subgroup can show.

• Members outside the US asked for help getting access there too.

Dr. Jessica Langbaum: should you join a prevention trial?

• Members asked whether joining a trial means stopping supplements and current routines, and whether giving up proven care for a placebo is fair.

• Others asked about equal access to trials across countries, how US residents can join trials abroad, and how AI is changing trials.

• A few shared mixed feelings about the chance of getting a placebo.

Dr. Aubrey de Grey: can repairing aging protect the APOE4 brain?

• Members framed APOE4 as speeding up normal aging and asked about rapamycin versus fasting and lifestyle for autophagy.

• Questions also covered senolytics, mitochondria, why he doubts NAD boosters, urolithin A, and which aging biomarkers are worth tracking.

Dr. Fatemeh Ramezani: the MIND diet, your gut and APOE4

• Members asked whether a vegetarian, dairy-free diet is enough for a carrier, and what to do if fermented foods do not agree with them.

• Others asked what to rely on when food allergies rule out whole food groups.

Dr. Kellyann Niotis: what APOE4 actually changes

• Continued from September: members asked whether early Alzheimer's blood markers can improve or only stay stable, and what obicetrapib might do for people with some amyloid.

• Others asked how desmosterol, a marker of cholesterol absorption, ties to brain health, and when the recording would be out.

Jodi Scott: stress, everyday exposures and what matters

• Members asked which free practices for calming the nervous system have evidence, including breathwork, meditation and Kirtan Kriya chanting.

• The other question: her view on sun exposure and sunscreen.

Brain health habits and everyday exposures

Weekly win: one thing for your brain this week

• Members shared small wins: a fixed bedtime, a paper book before bed, a meditation app, resistance training then sauna, swimming, a CGM experiment.

• Others cut mental load with a paper diary and to-do list, or tried hops and valerian, glycine or tart cherry for sleep.

Smell training at home instead of a pricey device

• A do-it-yourself version of overnight scent training (a timed fan and rotating essential oils) drew lots of interest as a cheap alternative.

• Members swapped favorite scents and setups; a researcher interview shared later said any varied scent works and timing is flexible.

• Several agreed the device is not worth the price until it shows benefits on par with diet and exercise.

High-altitude travel and the brain

• Members discussed whether trekking at very high altitude carries extra risk for carriers; little research exists on it.

• Advice centered on a gradual ascent, nights at a middle altitude to acclimatize, and watching where you sleep, not just the highest point.

• Experiences varied widely, and altitude medicine side effects were mentioned.

Choosing a home sauna

• Members discussed sauna benefits for the brain and compared infrared and traditional home saunas.

• Several said most long-term evidence comes from traditional Finnish saunas; owners described better relaxation and sleep.

September goals: supplement timing and sleep consistency

• Continued from early September: members discussed spacing psyllium about two hours from supplements and medicines so they still absorb.

• Others worked on keeping a regular bedtime and swapped what helped and what did not.

Mindfulness and journaling

• Members shared mindfulness reading and a simple daily photo-and-journal habit that eased stress and helped sleep.

• Others agreed mindfulness is an overlooked part of brain health.

Anesthesia choices for surgery

• Continued from earlier: a member shared a nurse anesthetist's view that a spinal anesthetic with light sedation can avoid general anesthesia for joint surgery.

Environmental exposures and dementia risk

• A shared Harvard study linked environmental exposures to dementia risk and proposed an "exposome" risk score; members found it fascinating.

Titanium dioxide in toothpaste

• A member flagged titanium dioxide nanoparticles in toothpaste as a possible brain irritant, noting the EU bans it in food but not toothpaste.

• Others checked their own toothpaste; members noted direct research is thin.

Blood vessels, inflammation and immunity

Small blood vessels in the brain

• A member's own notes on a vascular neurologist's podcast were valued for being human-written, not AI.

• Practical levers listed: exercise, blood pressure including at night, lipids, glucose, waist size and visceral fat, and sleep apnea.

• Left open: whether small-vessel damage can be repaired once a scan finds it; members asked to interview the podcast's guest.

Shingles vaccine

• Most members reported no reaction or a day of flu-like symptoms; rare stronger reactions were mentioned.

• The broad view: get it to avoid shingles itself and treat any dementia benefit as a bonus.

• Some pointed out the dementia data are observational and vaccinated people may simply be more health-conscious.

CRP inflammation and Alzheimer's risk in carriers

• A shared study found high CRP was linked to Alzheimer's only in APOE4 carriers, even though carriers usually run lower CRP.

• Members asked what else can drive inflammation, with poor sleep and sleep apnea discussed, and orexin sleep drugs came up as one option people use.

Brain immune cells replaced with age

• New studies suggest the brain's immune cells are replaced over time by inflammatory cells from the blood, opening ideas for new treatments.

• Members discussed related research where certain blood cell mutations delayed Alzheimer's in 4/4 carriers.

• Several voiced hope mixed with frustration that research moves too slowly.

APOE4 and an inflammatory immune signature

• A shared study found an APOE4-linked inflammatory immune pattern across blood, spinal fluid and brain, partly reversed by a medical ketogenic diet in 12 weeks.

Food, glucose and diet

More fiber without glucose spikes

• CGM wearers found legumes spike some people and not others; tips included small portions, eating fiber and protein first, and walking after meals.

• Easy wins shared: red lentils blended into sauces, psyllium, fermented foods, and checking restaurant sauces for hidden sugar.

• Several questioned chasing a perfectly flat glucose line, saying short rises that settle quickly are normal.

How many blueberries is enough?

• Prompted by an influencer's claim, members compared amounts, from a handful to a couple of cups a day.

• Wild frozen berries, black currants and red cabbage were popular; some CGM wearers saw spikes from berries.

• Several preferred variety over one superfood, such as aiming for 30 plants a week.

Finding genuine high-polyphenol olive oil

• Continued from earlier: members in the UK shared how to find olive oil that publishes tested polyphenol levels, since many brands make unverified claims.

Rapamycin

Rapamycin and brain blood flow in carriers

• A small University of Missouri trial found low-dose rapamycin raised brain blood flow only in APOE4 carriers, most in women.

• Long-term users shared positive experiences; a few stopped because their lipids and blood sugar worsened.

• Many described how hard it is to find a doctor willing to prescribe it for prevention; an SGLT2 diabetes drug also came up.

Rapamycin worries: blood sugar, lipids and dosing

• Members debated whether rapamycin raises blood sugar and cholesterol and blunts exercise gains, and whether weekly rather than daily use avoids that.

• In older threads, members said rising lipids are a common side effect, and discussed pausing it during antibiotics.

• Members outside the US said finding a doctor to prescribe and monitor it is especially hard.

Cholesterol and heart

MCT and coconut oil, and what they did to LDL

• Several carriers said MCT or coconut oil in coffee made their LDL soar, and stopping helped.

• A few wondered whether pure C8 oil behaves differently; experiences varied, and members agreed you only know by testing.

• Some said even a diet rich in healthy fats raised their LDL sharply.

Turmeric and statins: a possible interaction

• A member flagged that curcumin can raise blood levels of statins processed by the CYP3A4 pathway, unlike rosuvastatin or pravastatin.

• Members asked for an easy way to check supplement and drug interactions; curcumin with painkillers and bleeding risk also came up.

Statins for carriers: another perspective

• A shared article questioned statins again; members wished the science were settled.

• Replies mentioned CoQ10 alongside statins, and some preferring non-statin options such as ezetimibe, bempedoic acid or PCSK9 drugs.

Psyllium to lower LDL

• Continued from September: members explained psyllium traps bile acids, which modestly lowers LDL and ApoB, and swapped ways to take it.

Is a yearly carotid (CIMT) scan worth it?

• Continued from September: a member argued a quality carotid ultrasound is the best radiation-free way to track artery plaque and stroke risk.

• Another said their cardiologist considers these scans less reproducible than newer methods; the two views were not settled.

Devices and wearables

General chat: sleep tracker accuracy and brain training

• Members asked how accurate ring trackers are for deep sleep, and shared a newsletter on people who carry APOE4 yet avoid Alzheimer's.

• Members passed on BrainHQ discounts and noted some public libraries offer it free.

Wearables, HRV and a shared WHOOP team

• Members started a shared WHOOP team for motivation on movement and sleep.

• I shared that a sleep study showed my ring tracker was far off; members agreed to stick to one device and watch trends.

Light therapy (photobiomodulation) devices

• Continued from earlier: a long-time user asked whether the memory study used the nasal device alone or with the headset.

Living with APOE4

Feeling overwhelmed after learning your status

• Several members described spiraling into anxiety after learning they carry APOE4 and needing to pause prevention to recover emotionally.

• Many welcomed a new monthly peer-support group for women carriers, saying it is a lonely place to be.

Finding doctors who understand APOE4

• Continued from earlier: members said specialists often know little about APOE4.

• One approach shared: look for doctors whose reviews say they listen and help patients reach their goals.

Genetics and research data

Is whole genome sequencing worth it?

• Members compared what whole genome results gave them: drug and supplement processing, CoQ10 form, and searching for protective genes.

• Some found results stressful, others helpful for planning; the shared view was to choose what suits your personality.

Why some carriers never get Alzheimer's

• A Stanford study on carriers who stay healthy prompted wishes for a tool that scans your genome for resilience genes.

• Members raised the privacy trade-off of uploading genetic data to commercial AI tools.

Analyzing your own genome with a local AI

• A member described running an AI model on a home computer to analyze raw genetic data privately, including drug-response genes.

• Others were impressed and asked about the setup; the post noted some genes are hard to read accurately this way.

Does research apply equally to one copy and two copies?

• A member asked whether findings described for "the APOE4 brain" apply the same way to 3/4 and 4/4 carriers, and where to learn more.

Hormones and menopause

Starting estrogen patches later in life

• Members discussed whether starting hormone therapy well after menopause is worthwhile; several who started late reported clearer thinking and comfort benefits.

• A specialist's opposing view was shared: heart and clot risks are proven while brain benefits are not.

• Left open: the real balance for older women with two copies.

Which type of hormone therapy matters for the brain

• A shared study found estradiol, not other estrogens, linked to better memory and brain structure, especially in APOE4 carriers.

• Members noted it is observational, lacked dose and route details, and found it useful for their own decisions.

What members discussed, not medical advice: take anything here to your doctor.