#819: Rhonda Patrick, Ph.D. — Protocols for Fasting, Lowering Dementia Risk, Reversing Heart Aging, Using Sauna for Longevity (Hotter is Not Better), and a Few Supplements That Might Actually Matter

Hello boys and girls, ladies and germs. Tim Ferriss here. Welcome to The Tim Ferriss Show, where I deconstruct world-class performers and raid the toolkits of scientists who self-experiment. My guest is Rhonda Patrick, Ph.D.—biomedical scientist, founder of FoundMyFitness, and a repeat favorite. We text a lot about brain aging, metabolic health, omega-3s, sauna, fasting, and more. Today is the latest and greatest—very actionable: VO2 max and longevity, reversing heart aging, brain aging, fasting protocols, creatine, vitamin D, omega-3s, microplastics, and more. Let’s start personal: aging parents. What’s actually working for yours?

My parents weren’t active and didn’t eat particularly well, so I went for low-hanging fruit. A daily multivitamin—yes, the plain Centrum Silver used in three randomized trials—improved cognition in older adults over 2 years, roughly 2 years younger globally and about 4.8 years younger on episodic memory. These were older adults without diagnosed neurodegenerative disease. Vitamin D is another no-brainer—older adults make about four times less from sun exposure; deficiency is rampant.

Quick detour: I’m APOE3/4. Does that change how I should do vitamin D or omega-3s?

Vitamin D, no. Omega-3s, yes. APOE4 carriers tend to get less DHA into the brain. Higher doses help, and phospholipid forms are better for brain delivery. Eating fish provides phospholipid DHA; with supplements, getting to roughly 2 grams per day total omega-3 can increase phospholipid remodeling. Krill is phospholipid-rich but not very concentrated; salmon roe is a great food option. Mechanistically, APOE4 is linked to early blood–brain barrier changes; phospholipid transport helps bypass passive diffusion issues.

What are your parents actually taking now?

For my dad with Parkinson’s (diagnosed 2017): multivitamin, high-DHA omega-3 at about 2 grams per day, and ubiquinol (CoQ10). His progression has been surprisingly slow—still mostly a hand tremor after nearly a decade. I’d add sulforaphane if he’d take more pills. My mom takes sulforaphane (Avmacol, two advanced caps daily), multivitamin, vitamin D, and omega-3. Sulforaphane activates NRF2, boosts glutathione in plasma and brain, and upregulates phase 2 detox enzymes—helps excrete pollutants like benzene and potentially BPA. She reported tremor improvements within one to two weeks. Bonus: she joined a seniors CrossFit class three times per week and loves it—huge win for function and social engagement.

On omega-3 brands, my parents use high-DHA options like Xymogen and Pure Encapsulations—both third-party tested. For eyes, think AREDS2: lutein and zeaxanthin. I’m also exploring exogenous ketones for older relatives—case studies in Alzheimer’s are intriguing, though costly. I’ve hired a trainer to literally pick up my parents—compliance matters. I’m watching Klotho too. Want to go deeper on ketones and fasting?

Absolutely.

I’ve been doing sixteen–eight most days—roughly 2 p.m. to 9 p.m.—and my labs and OGTT improved dramatically. A recent seven-day water fast wiped out my chronic low-back pain for four weeks. I’m weighing water-only versus fasting-mimicking diets and “dirty” fasting like heavy cream in coffee. I want the benefits—metabolic, brain, autophagy—without huge muscle loss. Also, my relatives show metabolic syndrome, and Alzheimer’s is called type three diabetes, so I’m pursuing prevention.

Intermittent fasting often reduces intake by roughly 200 calories per day, driving weight loss. Even without weight loss, you see better fasting glucose, HbA1c, lipids, and blood pressure. Ketosis typically begins after around 12 hours once liver glycogen depletes—faster if active or lower carb. Beta-hydroxybutyrate is clean energy, anti-inflammatory, an HDAC inhibitor, and boosts BDNF. It spares glucose in the brain to support glutathione synthesis. Fasting also triggers repair—autophagy and mitophagy—which need a catabolic state. In humans, more robust autophagy signals appear around 24 to 48 hours, but there’s likely low-level nightly activity too.

Sleep matters for Alzheimer’s. Slow-wave sleep enhances glymphatic clearance. Drugs like Xyrem are interesting mechanistically but risky; even low-dose psilocybin is being explored. Point is: fix sleep architecture if you can.

Agree—slow-wave sleep ramps glymphatic clearance of amyloid. On muscle: with sixteen–eight plus resistance training, you can maintain or slightly gain muscle. Prolonged fasts do reduce lean mass—there’s big water loss and temporary organ shrinkage as damaged cells die; refeeding is the growth phase, so prioritize protein to rebuild. Visceral fat drops too. Any calories blunt autophagy—protein and leucine via mTOR are especially inhibitory. If you need coffee in the fasting window, small amounts of MCT oil or powder beat cream because you avoid amino acids and keep the ATP:AMP signal more favorable for AMPK.

Got it. Heavy cream is calorie-dense fat; MCT powder is a better compromise. I wish we had long-term fasting RCTs. Refeeding is tricky at longer durations.

With very long fasts, gallstone risk rises because the gallbladder isn’t stimulated; occasional long fasts may be fine, but caution is warranted.

Compliance-wise, IF is easier than dietary overhauls for many. Ketosis also helps my zone two. Let’s talk training—VO2 max and heart aging.

VO2 max is your maximal oxygen uptake—cardiorespiratory fitness and a strong longevity predictor. Low fitness carries all-cause mortality risk comparable to or worse than type two diabetes or smoking. Zone two is valuable but about 40 percent of people do not improve VO2 max without vigorous intervals. High-intensity interval training—above roughly 80 percent max heart rate—drives bigger adaptations like increased stroke volume. Protocols include four minutes hard with three minutes recovery repeated four times, one minute on/one minute off for ten rounds, or Tabatas.

What’s your personal mix?

Three days per week CrossFit with HIIT elements; Norwegian four-by-four on bike or rower (four minutes hard, three minutes easy, four rounds); one-minute intervals; Tabatas; plus two to three thirty-minute runs at zone two.

I’m adding the four-by-four even though it feels like being chased by wolves. Any confounders in VO2 max–longevity data?

Observational studies cannot prove causation, though measured fitness beats questionnaires and adjustments help. That is why randomized trials matter—like the heart-aging study.

Tell us about reversing heart aging.

Ben Levine’s team trained sedentary but otherwise healthy fifty-year-olds for two years, about five hours per week, including one to two Norwegian four-by-fours. Hearts in midlife typically shrink and stiffen; after training, participants’ hearts were larger and more compliant—roughly a 20-year reversal. Intensity is individualized—brisk walking can be “hard” at first. It is not too late to start.

Brain aging—can we get two birds with one stone?

Yes. Vigorous work shifts you toward anaerobic metabolism and raises lactate. Lactate is rapidly shuttled to brain and heart within about 20 minutes, used as clean energy, spares glucose for glutathione, and signals BDNF, norepinephrine, and serotonin. Human studies show hippocampal volume increases of about 1 to 2 percent over a year with training versus the typical decline. Resistance training also raises lactate. I prioritize vigorous work for neuroprotection given my family history.

Saunas: I’ve seen Finnish data—big reductions in all-cause mortality and dementia with higher frequency. How should we interpret that, and what temps and routines do you use?

The Finnish data are accurate and dose dependent. Mechanisms likely include cardiovascular benefits and heat shock proteins—sauna at roughly 163 degrees Fahrenheit for about 30 minutes boosts heat shock proteins around 50 percent. Early in my career, overexpressing heat shock proteins prevented toxic protein aggregation in worm models. One caution: a non-Finnish study suggested that very hot saunas—about 190 to 200 degrees Fahrenheit—were linked to increased dementia risk, while less than 190 degrees Fahrenheit was protective. You do not need extreme heat. I like 170 to 190 degrees Fahrenheit for around 20 minutes. Hot tubs and hot baths help too—about 104 degrees Fahrenheit for 20 minutes can produce comparable cardiovascular effects.

And fertility?

Sauna can lower sperm motility, but it reverses roughly six weeks after stopping. Do not use it as contraception.

Do you still use curcumin instead of NSAIDs?

Yes—Meriva phytosomal curcumin, two grams (four caps of 500 milligrams), often the Thorne brand. It helps my headaches and sometimes post-squat soreness.

Creatine: beyond the gym-bro lore, what actually works for brain and muscle?

Creatine stores as phosphocreatine and fuels quick energy—so you get more reps or an extra set, which drives strength and hypertrophy. The liver makes about 1 to 2 grams; five grams daily saturates muscle over time. For the brain, higher intakes matter because muscle is greedy. Studies using 20 to 25 grams during about 21 hours of sleep deprivation not only prevented cognitive decline but improved performance beyond baseline. Older adults improved cognition with 20 grams. A small Alzheimer’s pilot using 20 grams showed benefits. I now take 10 grams daily—if I skip it, I feel afternoon sleepiness. On heavy sleep debt days, I take about 20 grams for a clean cognitive boost without the caffeine jitters.

I metabolize caffeine fast—coffee lights me up for twenty-five minutes, then I crash. Quick creatine questions: were the twenty to twenty-five gram doses in one sitting or split? What form do you use when traveling—powder, sachets, capsules? And on sulforaphane, is empty stomach better or should I take it with food, especially if I am intermittent fasting and timing fat for absorption?

I stick with creatine monohydrate—the gold standard. I take five grams first thing in the morning and five grams after my workout for a total of ten grams. When traveling, I use five-gram sachets; if I need fifteen to twenty grams for heavy days, I split it into two ten-gram doses, which I tolerate well. Five-gram increments are gentler on the gut. For sulforaphane, fasted is great if your stomach tolerates it; otherwise take it with food only to avoid GI upset.

NSF Certified is my cheat code for quality—supplement contents vary wildly. Creatine can reduce cognitive deficit from sleep loss, but twenty grams in one go plus caffeine can be GI roulette. Given the safety and cost, I am going to increase. Now, vitamin D: despite five thousand international units daily and lots of sun, I barely squeak by on labs. Is the measurement the problem, or what am I missing?

We measure vitamin D by 25-hydroxyvitamin D, the liver-made precursor to the active steroid hormone 1,25-dihydroxyvitamin D. Converting D3 to 25-hydroxyvitamin D requires magnesium, and about fifty percent of Americans are magnesium-insufficient. Low magnesium correlates with low 25-hydroxyvitamin D. Genetics can blunt cutaneous D3 synthesis. Supplement labels can be off—some underdose, some overdose. Skin pigmentation matters too; darker skin has more melanin, so African Americans may need approximately six to ten times more sun to make the same D3. Sunscreen and other variables also play a role.

So what levels do you aim for, how much should I take if I am around thirty nanograms per milliliter, and what type and dose of magnesium? Also, any vitamin D and magnesium brands you like?

I like forty to sixty nanograms per milliliter, up to eighty is still fine; fifty is a great target. If you are at thirty, five thousand international units per day plus summer sun should get you near fifty; if not, try seven thousand international units and retest in one month. You have to individualize by testing. For magnesium, men around four hundred milligrams daily and women around three hundred, with ten to twenty percent more if you sweat a lot. Prefer citrate, malate, taurate, or glycinate; avoid oxide. Magnesium threonate may cross the blood-brain barrier, but I still take glycinate so peripheral tissues get magnesium for vitamin D conversion. Count electrolytes and food toward your total.

I use Pure Encapsulations vitamin D; VesiSorb D3 can help poor absorbers and also boosts ubiquinol and some fish oil bioavailability. I use Pure Encapsulations magnesium glycinate and Xymogen magnesium threonate.

Can we hit microplastics and mitigation—and is a Berkey countertop filter effective?

Microplastics are everywhere: tap water, plastic bottles, gum labeled with “gum base” polymers, and tea bags that shed thousands of particles. Reverse osmosis is best and can catch nano; Berkey removes micro but nano is unclear. Even glass bottles can have plastic from lid paints, but those particles are larger and less absorbed; I still choose glass over plastic. Avoid hot drinks in plastic-lined paper cups; heat spikes microplastics and BPA leaching. Blue Bottle uses sugarcane polylactic acid liners; otherwise bring your own cup. Use loose-leaf tea with a metal infuser. Evidence for “detox” is thin, but sulforaphane induces detox enzymes that excrete BPA in urine in animal studies. Priority one is reducing exposure.

Endocrine disruptors in fragranced products worry me for male fertility. I knew about tea bags and filtration, but not gum. A relative with Alzheimer disease chewed several packs a day—I now wonder.

Same. I used xylitol gum for oral health and even reversed early cavities, then learned most gum bases are plastic. I switched to microplastic-free xylitol gum made from tree resins, and xylitol mints also work.

On alcohol: some studies suggest moderate intake helps, but is that confounded by social factors and sick quitters? What do you actually recommend, and what mechanisms link alcohol to cancer and dementia?

Many “moderate is protective” papers failed to exclude sick quitters and rarely stratified by APOE genotype, so the benefits are suspect. Cancer risk is unambiguous: alcohol is a group one carcinogen. Even moderate intake raises breast and colon cancer risk; for women, lifetime breast cancer risk can move from about one in eight to roughly one in six. The safest dose is zero; if you drink, one to two drinks per week is the lowest-risk zone. Fitness can blunt some dementia associations, but do not silo alcohol from the rest of lifestyle.

Beyond acetaldehyde as a mutagen, what else is at play? And anecdotally, when I am in ketosis above about one point two millimoles per liter, alcohol hits me much harder. A lot of friends are swapping alcohol for ketamine, which I think is a risky trade.

Mechanisms include acetaldehyde DNA damage, alcohol-induced gut permeability and lipopolysaccharide-driven inflammation, oxidative stress, blood-brain barrier disruption, and mitochondrial impairment. APOE4 carriers have weaker repair and may be more vulnerable. Alcohol also wrecks sleep architecture, especially REM, which ties to dementia risk; avoid drinking near bedtime. I rarely drink now—maybe a celebratory glass here and there.

On safer alternatives, psilocybin looks promising for major depressive disorder and alcohol use disorder. I saw the Emory mouse study suggesting approximately twenty percent life extension, though dosing translation is tricky. I have funded work showing strong anti-inflammatory effects from various psychedelics at sub-perceptual, even nano-dose levels. My hunch is that a lot of benefit across fasting, ketosis, cold exposure, exogenous ketones, vagus nerve stimulation, psilocybin, and compounds like sulforaphane and curcumin flows through reducing chronic inflammation and neuroinflammation. I am testing stacks at minimal effective doses and plan to measure ex vivo cytokine responses in my white blood cells.

I agree the anti-inflammatory pathway could be central. Psilocybin is not addictive, has human data for depression and alcohol use disorder, and that mouse longevity signal is intriguing. Targeting chronic neuroinflammation is likely key for reducing later-life neurodegeneration.