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FoundMyFitness · 2023-12-27 · Rhonda Patrick (host), Peter Attia

Dr. Peter Attia on Mastering Longevity – Insights on Cancer Prevention, Heart Disease, and Aging

135 research-tied claims examined: 13 contradicted 8 overstated 16 context 83 supported 15 unverified

13

Contradicted by research

0:29:45Peter Attiacontradictedhigh

Most animal species do not have ApoB and do not require LDL.

"most species don't have ApoB. They don't require LDL." (said at 0:29:45)

Apolipoprotein B (ApoB) is conserved across all vertebrate species (including mammals, birds, reptiles, amphibians, and fish), where it serves as the essential structural scaffold for atherogenic lipoproteins including VLDL and LDL. Furthermore, evolutionary phylogenetic analyses show that ApoB belongs to the ancient large lipid transfer protein (LLTP) superfamily that evolved in the earliest multicellular animals; invertebrates utilize direct ApoB homologues (such as insect apolipophorin II/I and crustacean apolipocrustacein) along with low-density lipoprotein receptor (LDLR) homologues to transport circulatory lipids.

0:49:56Peter Attiacontradictedhigh

Individuals with loss-of-function mutations in PCSK9 and lifelong low LDL-C exhibit no increased incidence of cancer, neurodegenerative disease, or diabetes.

"what I did confirm is they have no increase in the incidence of any other disease. So in other words, they're absent ASCVD, but they don't make up for it with more cancer or more neurodegenerative disease or more diabetes." (said at 0:49:56)

While individuals with loss-of-function variants in PCSK9 and genetically lower LDL-C show no increased risk of cancer or neurodegenerative disease/dementia, large-scale genetic association and Mendelian randomization studies consistently demonstrate that lifelong genetically proxied PCSK9 inhibition is associated with a modest, statistically significant increase in the risk of type 2 diabetes, similar to other LDL-lowering targets such as HMGCR and NPC1L1.

1:19:00Peter Attiacontradictedhigh

In the central nervous system, cholesterol synthesis occurs exclusively through the desmosterol pathway, making circulating desmosterol a proxy for brain cholesterol synthesis, whereas lathosterol reflects peripheral cholesterol synthesis.

"Remember how I said there were two cholesterol synthesis pathways? Well, in the CNS, really only you have one pathway, and it's the pathway that goes through desmosterol to cholesterol. So desmosterol levels are actually a decent proxy for brain cholesterol synthesis. Lathosterol, which is the penultimate molecule in the other pathway, is more of a proxy for peripheral cholesterol synthesis." (said at 1:19:00)

The speaker claims that cholesterol synthesis in the central nervous system (CNS) occurs exclusively via the desmosterol pathway, leaving lathosterol as solely a peripheral proxy. However, direct analytical measurement of sterols in human and rodent brain tissue shows that both major cholesterol synthesis pathways—the Bloch pathway (yielding desmosterol) and the Kandutsch-Russell pathway (yielding lathosterol)—are active in the CNS. Gas chromatography-mass spectrometry studies of human post-mortem brain regions and cerebrospinal fluid (CSF) routinely detect and quantify lathosterol alongside desmosterol as an endogenous precursor of brain cholesterol synthesis. Although circulating desmosterol and lathosterol ratios are often studied as relative indicators for cerebral versus systemic cholesterol turnover, the assertion that the CNS operates using only the desmosterol pathway is contradicted by lipidomic evidence.

1:21:02Peter Attiacontradictedmoderate

No clinical research studies have evaluated whether circulating desmosterol levels differ in individuals carrying the APOE4 allele.

"no one has done the study to show, are desmosterol levels lower in APOE4 individuals?" (said at 1:21:02)

Clinical studies have measured circulating cholesterol synthesis markers, including desmosterol, across APOE genotypes. For example, in a prospective clinical cohort study comparing healthy children carrying the APOE4 phenotype against APOE 3/3 individuals, researchers quantified serum desmosterol and lathosterol using gas-liquid chromatography to evaluate whether endogenous cholesterol synthesis differed by APOE allele status.

1:28:36Peter Attiacontradictedhigh

Bempedoic acid does not increase the risk of developing type 2 diabetes.

"But no side effects, no type 2 diabetes risk, nothing. It's just—it's only acting in the liver." (said at 1:28:36)

The speaker's statement bundles two distinct assertions: that bempedoic acid does not increase the risk of type 2 diabetes, and that it has "no side effects, nothing." 1. Risk of Type 2 Diabetes: Supported. Large randomized controlled trial evidence confirms that bempedoic acid does not increase the risk of developing type 2 diabetes or worsen glycated hemoglobin (HbA1c). In the CLEAR Outcomes trial (13,970 participants), new-onset diabetes occurred in 11.1% of participants taking bempedoic acid compared to 11.5% on placebo (HR 0.95; 95% CI 0.83–1.09) (PMID 38061370). Meta-analyses of randomized trials similarly demonstrate no increased risk of new-onset or worsening diabetes compared to placebo (PMID 32787939). 2. Absence of Side Effects: Contradicted. The claim that bempedoic acid has no side effects is inaccurate. Systematic reviews and meta-analyses of randomized trials show that bempedoic acid is associated with recognized adverse effects, notably an increased risk of hyperuricemia and gout (OR 1.55; 95% CI 1.27–1.90) (PMID 38017541). Because the statement asserts that bempedoic acid produces "no side effects, nothing," the overall claim is contradicted by clinical evidence.

1:50:38Peter Attiacontradictedmoderate

All-cause mortality data show better outcomes for individuals with a hemoglobin A1c of 5.0% compared to 5.5%.

"And what the hemoglobin A1c data would suggest is being at 5%, which is about an average of 100, is better than being at 5.5%, which is an average in the 115 range. Both of those are normal by our current definitions. Neither of those would be pre-diabetic even. So 5 and 5.5 are both considered completely normal levels, but the all-cause mortality data, or the data on all-cause mortality, suggest a better outcome if you're at 5 rather than 5.5." (said at 1:50:38)

Epidemiological cohort studies and meta-analyses investigating the relationship between glycated hemoglobin (HbA1c) and all-cause mortality in non-diabetic populations demonstrate a J-shaped or U-shaped curve, not a linear decline showing superiority of 5.0% over 5.5%. The nadir of lowest all-cause mortality consistently spans the range of 5.0% to 5.9% (with 5.0% to <5.5% commonly used as the lowest-risk reference category), and individuals with HbA1c levels below 5.0% frequently exhibit higher, not lower, all-cause mortality due to confounding factors such as malnutrition, liver disease, and anemia. Observational data do not show superior survival at an HbA1c of 5.0% compared to 5.5%.

2:15:21Peter Attiacontradictedhigh

Patients with stage III colon cancer treated with surgical resection and the 3-drug FOLFOX chemotherapy regimen have a 65% 5-year survival rate, whereas stage IV colon cancer patients with visible liver metastases have a 0% 5-year survival rate after the same chemotherapy.

"If you give that patient the FOLFOX regimen, which is the standard chemotherapy regimen, that's three drugs, 65% of those patients will be alive in five years. So a third of them will still die, but two-thirds of them will live. If that exact same patient, when you go in and you take their colon out and you take their lymph nodes out, also has visible metastatic disease in the liver, they're now stage four. After surgery, they will go on to get the same chemotherapy. None of those people will be alive in five years." (said at 2:15:21)

The claim bundles two assertions. The first assertion—that approximately two-thirds of stage III colon cancer patients treated with surgical resection and FOLFOX chemotherapy survive long-term—is well supported; the landmark MOSAIC randomized trial demonstrated a 10-year overall survival rate of 67.1% for stage III disease receiving adjuvant FOLFOX4. However, the second assertion—that stage IV patients with visible liver metastases have a 0% 5-year survival rate after surgery and chemotherapy ('none of those people will be alive in five years')—is contradicted by extensive clinical evidence. In patients with colorectal cancer liver metastases undergoing resection and systemic chemotherapy regimens such as FOLFOX, 5-year overall survival rates consistently range between 30% and 50% or higher.

2:22:35Peter Attiacontradictedhigh

Colonoscopy has a 100% sensitivity for colorectal cancer screening.

"A colonoscopy is a test that has 100% sensitivity and very high specificity" (said at 2:22:35)

Colonoscopy does not have 100% sensitivity for detecting colorectal neoplasia or precursor lesions. Large meta-analyses of tandem colonoscopy studies demonstrate substantial miss rates. A meta-analysis of 43 tandem colonoscopy studies (over 15,000 procedures) established a pooled adenoma miss rate of 26% (95% CI: 23%–30%), an advanced adenoma miss rate of 9% (95% CI: 4%–16%), and a serrated polyp miss rate of 27% (95% CI: 16%–40%). A subsequent meta-analysis found an overall adenoma miss rate of 34% (95% CI: 30%–38%) and an advanced adenoma miss rate of 21% for conventional white-light colonoscopy, demonstrating that false negatives occur and contribute to post-colonoscopy interval cancers.

2:23:33Peter Attiacontradictedhigh

A New England Journal of Medicine study on colonoscopy involving over 20,000 participants reported not a single procedural complication incident.

"if you look at the largest study that came out on this, which was last summer in the New England Journal of Medicine, this was actually a study that was meant to show that colonoscopy wasn't worth it, actually showed something totally different in my mind, which showed how safe it was. So it was a study of I think over 20,000 people and had not a single incident." (said at 2:23:33)

The speaker refers to the NordICC trial published in The New England Journal of Medicine (Bretthauer et al., 2022), which evaluated screening colonoscopy in 84,585 participants (28,220 assigned to the invited group, of whom 11,843 underwent screening). While the trial reported zero perforations and zero screening-related deaths within 30 days of colonoscopy, it did not report zero adverse incidents: a total of 15 participants experienced major bleeding after polyp removal.

2:32:26Peter Attiacontradictedhigh

Small cell, large cell, and squamous cell carcinomas are the predominant types of lung cancer that occur in tobacco smokers.

"small cell, large cell, and squamous cell are the dominant cancers that occur in smokers" (said at 2:32:26)

The statement claims that small cell, large cell, and squamous cell carcinomas are the dominant types of lung cancer in smokers. While squamous cell carcinoma and small cell carcinoma have strong etiologic links to tobacco smoking, epidemiological surveillance data demonstrate that adenocarcinoma is the most common histological subtype of lung cancer overall and in smokers, having surpassed squamous cell carcinoma in prevalence over recent decades. Excluding adenocarcinoma from the primary histological subtypes of lung cancer in smokers is inaccurate.

2:35:55Peter Attiacontradictedhigh

Molecular breast imaging (MBI) delivered approximately 20 to 30 millisieverts of radiation.

"It's called, I think it was called molecular breast imaging. It was another high-intensity mammogram. It's, again, I've never seen one done, I don't think they've been done in years, but pre-MRI, like pre-utility for other tests, it was done. It was also about a 20 to 30 mSv..." (said at 2:35:55)

The claim that molecular breast imaging (MBI) delivered 20 to 30 millisieverts (mSv) of radiation is contradicted by published dosimetry data. Modern screening MBI using direct-conversion cadmium zinc telluride (CZT) gamma cameras and lower administered activities of [99mTc]Tc-sestamibi (approximately 300 MBq / 8 mCi) imparts an effective whole-body radiation dose of approximately 2.4 mSv. Even older, conventional scintimammography and early MBI protocols using higher activities (740–925 MBq / 20–25 mCi) delivered whole-body effective doses in the range of approximately 6 to 9 mSv, well below the claimed 20 to 30 mSv.

2:35:40Peter Attiacontradictedhigh

In reproductive-aged premenopausal women, absolute testosterone levels are at least 10 times higher than estrogen levels at peak ovulation and up to 100 times higher in follicular or luteal phases.

"Your testosterone right now is at least 10 times higher than your estrogen level. In absolute quantities. And by the way, that's the highest—that's if you're ovulating, so your peak estrogen is around ovulation. If I take you in the early follicular cycle or in the luteal cycle, your testosterone could be 100 times higher than your estrogen." (said at 2:35:40)

The speaker's claim regarding the absolute ratio of testosterone to estrogen (estradiol) across the menstrual cycle is contradicted by standard endocrine measurements. In healthy premenopausal women, circulating total testosterone typically ranges from 15 to 70 ng/dL (150 to 700 pg/mL, or ~0.5 to 2.4 nmol/L). In comparison, estradiol fluctuates between approximately 30–60 pg/mL in the early follicular phase, peaks at roughly 200–400 pg/mL around ovulation, and remains elevated at 100–200 pg/mL during the mid-luteal phase. Consequently, in absolute mass concentrations (pg/mL): 1. At peak ovulation (estradiol ~200–400 pg/mL vs. testosterone ~300–500 pg/mL), testosterone and estradiol levels are roughly comparable (approx. a 1:1 to 2:1 ratio), not "at least 10 times higher". 2. In the early follicular phase, testosterone is typically 5 to 10 times higher than estradiol, not 100 times higher. 3. In the mid-luteal phase, estradiol rises substantially, reducing the testosterone-to-estradiol ratio to approximately 2:1 to 4:1. The speaker appears to have made a unit conversion error (e.g., comparing testosterone reported in ng/dL directly against estradiol reported in pg/mL without converting units, where 1 ng/dL equals 10 pg/mL).

2:59:55Rhonda Patrick (host)contradictedmoderate

In the Danish Osteoporosis Prevention Study (DOPS), women receiving hormone replacement therapy for 11 years had reduced cardiovascular disease mortality and heart failure risk over 16 years of follow-up without increased thromboembolism or cancer.

"And both of those studies—in the in the DOPS one, um, the the initiation of the—they did uh estradiol, I think they did like triphasic or something, but also they did the progesterone, so it had progestin as well. Um, it was like the the cardiovascular disease risk or mortality went down, the venous thromboembolism, like the things that happen, um, that can increase with uh menopause went down over the follow-up, which was 16 years or something." (said at 2:59:55)

In the Danish Osteoporosis Prevention Study (DOPS; PMID 23048011), 1,006 recently postmenopausal women received either hormone replacement therapy (oral estradiol with or without norethisterone acetate) for approximately 11 years or no treatment, with 16 years of follow-up. The primary composite endpoint of mortality, myocardial infarction, or hospitalization for heart failure was significantly reduced in the treated group (HR 0.48, 95% CI 0.26 to 0.87). However, venous thromboembolism (VTE) did not decrease: deep vein thrombosis occurred in 2 treated women versus 1 control participant (HR 2.01, 95% CI 0.18 to 22.16), showing no significant increase but certainly no reduction. Because the speaker asserted that venous thromboembolism risk went down, that specific relationship is contradicted by the trial's findings.

Unverified means no publication matching the claim was located; it does not prove the claim false. Spotted an error? See the corrections policy - disputes from the people quoted are prioritized.