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Cholesterol

Episodes

Posted on June 9th 2025 (8 days)

Dr. Rhonda Patrick discusses coffee's remarkable ability to slow biological aging, reduce DNA damage, and lower cancer risk.

Posted on May 15th 2025 (about 1 month)

Dr. Rhonda Patrick discusses cancer prevention, linoleic acid, shingles vaccine and dementia, creatine's kidney effects, and shares her overnight oats recipe.

Posted on March 14th 2025 (3 months)

Dr. Rhonda Patrick discusses saturated fats and LDL, luteolin's benefits, glyphosate risks, natural vs. artificial flavors, and black cumin seed effects.

Topic Pages

  • Carotenoids

    Carotenoids and cholesterol co-absorb via mixed micelles, share NPC1L1 and SR-B1 transporters, and carotenoids modulate hepatic cholesterol metabolism.

  • Cold exposure

    Cold exposure activates adrenergic brown adipose thermogenesis, enhancing LDL receptor–mediated hepatic clearance and biliary cholesterol excretion.

  • Sugar-sweetened beverages (SSBs)

    Fructose-laden SSBs accelerate hepatic de novo lipogenesis, boosting VLDL secretion, raising LDL cholesterol and lowering HDL levels.

News & Publications

  • Eggs are a dietary paradox: high in cholesterol but rich in brain-boosting nutrients, including choline, lutein, and zeaxanthin. While some studies indicate that eggs maintain cognitive health, others report the converse. A recent study found that eating eggs may help women preserve semantic memory—crucial for language comprehension and factual recall—as they age.

    Researchers analyzed data from 890 adults aged 55 and older. Participants reported their egg consumption using a food frequency questionnaire, and researchers measured their memory and thinking skills at two clinic visits about four years apart.

    They found that women who ate five eggs weekly experienced less decline in verbal fluency, a measure of semantic memory, than those who ate fewer eggs. In men, researchers found no clear relationship between egg intake and changes in cognitive performance. Eating eggs did not appear to harm cognitive function in either sex.

    These findings suggest that eggs play a small but beneficial role in preserving memory in women. They also align with other research demonstrating that people with moderate choline intake—roughly the amount in two eggs—are about half as likely to have low cognitive function than those with the lowest intake.

  • Nearly half a million women in the US die from cardiovascular disease every year, making early identification of those at risk crucial. Traditional identification methods, which focus on age, blood pressure, smoking status, cholesterol levels, and family history, address short-term risks, but longer-term predictions may improve outcomes. A recent study found that measuring specific blood markers can predict cardiovascular events over a 30-year period in women.

    The study involved nearly 28,000 healthy US women. Researchers measured three key biomarkers: high-sensitivity C-reactive protein (hs-CRP), low-density lipoprotein cholesterol (LDL), and lipoprotein(a) [Lp(a)]. Then, they tracked the women’s health for 30 years to observe their first major cardiovascular event, including heart attack, stroke, or death from cardiovascular causes.

    They found that women with the highest levels of hs-CRP were 70% more likely to experience a cardiovascular event than those with the lowest levels. Similarly, those with the highest LDL and Lp(a) levels were 36% and 33% more likely, respectively, to have a heart attack or stroke. Each biomarker contributed independently to overall cardiovascular risk, with the strongest predictive power coming from a combination of all three markers.

    These findings suggest that long-term cardiovascular risk prediction in women can be improved by measuring these biomarkers early in life. This proactive approach could lead to earlier interventions, potentially reducing heart disease risk over several decades.

  • Lipoprotein(a) [Lp(a)] is a type of low-density lipoprotein (LDL). High Lp(a) levels increase a person’s risk for atherosclerosis, heart disease, and stroke. A recent study found that alpha-linolenic acid (ALA) and linoleic acid (LA) both reduce Lp(a) concentrations in healthy men, but ALA is more effective at lowering cholesterol.

    The study involved 130 men enrolled in an ongoing cohort study in Finland. Researchers provided the participants with diets enriched in either ALA, an omega-3 fatty acid, or LA, an omega-6 fatty acid, for eight weeks.

    They found that serum Lp(a) concentrations dropped 7.3% among those who ate the ALA-rich diet and 9.5% among those who ate the LA-rich diet. Reductions were greater among those with higher baseline Lp(a) concentrations. However, those who ate the ALA diet experienced greater reductions in LDL cholesterol, apolipoprotein B, and other cholesterol components. Whether the participants carried the FADS1 rs174550 genotype did not influence their response to the diets.

    The FADS1 rs174550 is a genetic variant that influences the body’s ability to convert certain fatty acids. This variant can affect how efficiently omega-3 and omega-6 fatty acids are metabolized, potentially influencing lipid levels and overall health.

    These findings suggest that ALA and LA exert similar Lp(a)-lowering effects, but ALA may be more effective at lowering cholesterol and other atherogenic factors. Learn more about Lp(a) in this Q&A featuring Dr. Rhonda Patrick.

  • Metabolic syndrome is a cluster of conditions that includes hypertension, high blood glucose, excess abdominal fat, and abnormal blood lipids. Having metabolic syndrome markedly increases a person’s risk of cardiovascular disease, type 2 diabetes, and stroke. A recent meta-analysis found that taurine supplementation improves conditions associated with metabolic syndrome.

    Researchers analyzed the findings of 25 studies (with more than 1,000 participants) investigating links between taurine supplementation and metabolic syndrome. They also explored the effects of taurine dose and examined secondary outcomes of taurine supplementation, including body composition, lipid profile, and blood glucose control.

    They found that taurine doses ranged from 0.5 to 6 grams, with study durations ranging from five days to one year. On average, taurine supplementation reduced systolic blood pressure by 4 mmHg, diastolic blood pressure by 1.5 mmHg, fasting blood glucose by 6 milligrams per deciliter, and triglycerides by 18 milligrams per deciliter. The researchers did not observe an effect on high-density lipoprotein cholesterol. The reduction in diastolic blood pressure and fasting blood glucose was dose-dependent, with higher doses eliciting more robust effects.

    These findings suggest that taurine supplementation improves factors associated with metabolic syndrome. Interestingly, other research shows that an acute bout of exercise increases blood taurine levels, providing a mechanistic link between exercise and better metabolic health.

  • Plant-based meat substitutes are made from non-meat sources, such as legumes or wheat gluten. They typically mimic the sensory profile of meat products and are popular among those wishing to reduce their animal protein intake for ethical or health reasons. A recent study found that plant-based meat substitutes did not benefit cardiometabolic health in people at risk for type 2 diabetes.

    The study involved 82 adults at risk for type 2 diabetes. Half of the participants ate an animal-based diet, while the others swapped out their usual animal-based foods for plant-based meat substitutes. Researchers assessed their blood lipids (triglycerides, LDL, HDL, and total cholesterol), glycemic control, insulin sensitivity, and blood pressure before and after the eight-week intervention.

    They found that participants who ate the plant-based meat substitutes had higher fiber, sodium, and potassium intake than those who ate animal meat. Their blood lipids showed little improvement, but their diastolic blood pressure decreased, and their insulin sensitivity increased. However, those who ate the animal meat diet had better glycemic control than those on the plant-based diet.

    These findings suggest that plant-based meat substitutes don’t improve cardiometabolic health in people at risk for type 2 diabetes. However, robust evidence demonstrates that high-intensity interval training (HIIT) profoundly affects cardiometabolic health. Learn more in this episode featuring Dr. Martin Gibala.

  • Statins are among the most widely prescribed drugs in the U.S., with more than 92 million users reported in 2018. Although the drugs are generally effective, nearly 22 percent of statin users with cardiovascular disease will experience a major adverse cardiovascular event within five years of drug initiation – a phenomenon known as “residual risk.” Findings from a recent meta-analysis indicate that combined statin-omega-3 therapy markedly reduces the risk of major adverse cardiovascular events and improves lipid and inflammatory markers.

    Researchers analyzed the findings of 14 randomized controlled trials involving more than 40,000 participants. The trials investigated links between statin use, omega-3s, and the risk of cardiovascular disease and related death. Omega-3 doses varied, ranging from 930 milligrams to 4,000 milligrams daily. However, most studies provided a dose of 1,800 milligrams daily.

    They found that combined statin-omega-3 therapy reduced the residual risk of experiencing myocardial infarction (heart attack) by 28 percent, a major adverse cardiovascular event by 15 percent, angina (chest pain) by 25 percent, and hospitalization for angina by 25 percent. Those receiving the combined treatment also experienced decreased cholesterol, triglycerides, and hsCRP (a marker of inflammation). However, the combined therapy did not reduce the residual risk of fatal and non-fatal stroke, coronary revascularization, and cardiovascular disease-related death.

    These findings suggest that combined statin-omega-3 therapy reduces the residual cardiovascular risks associated with statin therapy alone. Learn more about statins in this episode featuring Dr. Peter Attia.

  • Statins comprise a large class of drugs that lower blood cholesterol levels by blocking the production of an enzyme involved in cholesterol synthesis. Although statins are generally well tolerated, as many as 10 to 20 percent of people taking the drugs experience complications, including myopathy (muscle damage), liver damage, and cognitive problems. A recent study found that atorvastatin, a commonly prescribed statin, reduces muscle cells' energy production.

    The study involved eight inactive but otherwise healthy adults with overweight who took a high dose of atorvastatin (80 milligrams) daily for 56 days. Researchers collected muscle samples from the participants before they took the statin and then again after 14, 28, and 56 days to assess their muscle cells' capacity for energy production.

    They found that over the 56 days, the muscle cells' ability to produce energy via oxidative phosphorylation diminished by more than 30 percent. Additionally, the muscle’s capacity to use oxygen, a key indicator of cardiorespiratory fitness, dropped by as much as 45 percent. The study investigators attributed this decline to the statin’s inhibition of specific components (complexes III and IV) within the mitochondria that are vital for energy production.

    The findings from this very small study shed light on how high-dose atorvastatin therapy can significantly reduce the energy production in muscle cells, driving a decrease in muscle and aerobic fitness. They also underscore the importance of further research in larger groups to balance the health benefits of statins with their potential effects on muscle function. Learn more about statins in this deep-dive discussion with Dr. Peter Attia.

  • Coronary artery disease, a cardiovascular condition characterized by the gradual buildup of plaque within the heart’s arteries, is the third leading cause of death worldwide, claiming the lives of nearly 18 million people each year. A recent meta-analysis found that omega-3 fatty acids reduced the risk of dying from cardiovascular disease by 18 percent and myocardial infarction (heart attack) by 23 percent, underscoring omega-3s' effectiveness as an adjunct therapy for coronary artery disease.

    The investigators analyzed the findings of 12 studies involving more than 29,000 people with coronary artery disease. The various studies lasted between one and five years and used both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), marine forms of omega-3 fatty acids. Doses ranged between 0.84 and 3.46 grams daily for EPA + DHA and between 1.8 and 4 grams daily for EPA alone.

    The analysis revealed that omega-3s reduced the risk of premature death from all causes by 10 percent, cardiovascular disease by 18 percent, myocardial infarction by 23 percent, sudden cardiac death by 33 percent, and hospitalization for heart failure or unstable angina pectoris (chest pain caused by lack of blood flow to the heart) by 25 percent in patients with coronary artery disease. These effects were strongest among patients receiving EPA only and those with high triglycerides.

    These findings suggest that omega-3s, especially EPA, reduce the risk of cardiovascular disease, particularly among people with high triglycerides. Triglycerides play critical roles in the pathophysiology of coronary artery disease. Elevated triglyceride levels often accompany other conditions, such as obesity, diabetes, and high LDL (“bad”) cholesterol, further exacerbating the risk of developing coronary artery disease. Learn about the early research showing omega-3s' effects on reducing triglycerides.

  • Time-restricted eating is a dietary pattern that restricts the time during which a person eats to a specific window, such as a “16:8" pattern, where they fast for 16 hours a day and consume food only during the remaining eight hours. Evidence suggests that time-restricted eating improves cognitive function, supports weight loss, and reduces systemic inflammation. Findings from a recent review and meta-analysis suggest that time-restricted eating also reduces the risk of cardiovascular disease.

    Researchers analyzed the findings of 33 studies involving 1,725 participants investigating the effects of time-restricted eating on markers of cardiovascular health. They conducted a sub-group analysis to determine how age, health characteristics, and eating patterns influenced the effects of time-restricted eating.

    They found that the effects of time-restricted eating on cardiovascular disease varied according to a person’s risk factors, age, and when they ate. The table below presents their findings for the optimal time-restricted eating for different groups.

    This meta-analysis and review identifies the optimal time-restricted eating interventions for blood pressure, obesity, lipids, and glucose. It effectively provides a best-practices guide for people interested in implementing time-restricted eating as a lifestyle modification to improve cardiovascular health. Learn more about time-restricted eating in this episode featuring Dr. Satchin Panda.

  • Children with overweight or obesity can develop nonalcoholic steatohepatitis (NASH) – an inflammatory condition in which fat builds up in the liver, replacing healthy tissue. Without intervention, NASH can progress to more advanced forms of liver disease, including cirrhosis and cancer. A recent study found that zinc supplementation improved liver function in children with NASH.

    Researchers gave 60 children with NASH either 30 milligrams of zinc or a placebo daily for four months. Before and after the intervention, they assessed the children’s liver function via ultrasound and measured their liver and inflammatory biomarkers.

    They found that the children who received the zinc supplements had lower serum alanine aminotransferase (a marker of liver damage) and C-reactive protein (a marker of inflammation) than those who took the placebo. They also had higher HDL (“good”) cholesterol.

    The findings from this small study suggest that zinc supplementation improves liver function and reduces liver inflammation in children with NASH. Further study may provide additional evidence supporting zinc’s use in NASH.

    Zinc is an essential nutrient. It plays roles in immune function, protein synthesis, wound healing, DNA synthesis, and cell division and modulates the activity of more than 300 enzymes and 2,000 transcription factors. Learn more about zinc in our comprehensive overview article.

  • From the publication:

    Per- and polyfluoroalkyl substances (PFAS), previously referred to as “perfluorinated compounds”, are a class of manufactured chemicals that have been detected in nearly all sampling of geographic locations and environmental matrices worldwide, including sites that had no nearby manufacture or use of PFAS. PFAS are used in hundreds of industrial and consumer products including food packaging and waterproof/stain resistant fabrics. Their strong carbon-fluorine bonds provide both hydrophobic and oleophobic properties, which make these chemicals extremely persistent in the environment. The class of PFAS includes tens of thousands of potential environmental contaminants including over one thousand chemicals previously or currently approved for use in the U.S..

    For PFAS measured at concentrations already found in the general population, exposure may suppress the immune system. Additionally, exposure to PFAS, with most studies on PFOA and PFOS, has been associated with many health harms, including an increased risk of cancer, high cholesterol, thyroid disease, and reproductive and developmental harms.

    The median level of total targeted PFAS in fish fillets from rivers and streams across the United States was 9,500 ng/kg, with a median level of 11,800 ng/kg in the Great Lakes. PFOS was the largest contributor to total PFAS levels, averaging 74% of the total. The median levels of total detected PFAS in freshwater fish across the United States were 278 times higher than levels in commercially relevant fish tested by the U.S. Food and Drug Administration in 2019–2022. Exposure assessment suggests that a single serving of freshwater fish per year with the median level of PFAS as detected by the U.S. EPA monitoring programs translates into a significant increase of PFOS levels in blood serum.

    Additional information:

    In June 2018, the Agency for Toxic Substances and Disease Registry (ATSDR) released a draft Toxicological Profile that derived minimal risk levels (MRLs), which are similar to RfDs, for intermediate duration exposure (15–364 days) of four PFAS routinely measured in NHANES [28]. The MRL [minimal risk levels] values for PFOA (3 ng/kg/day) and PFOS (2 ng/kg/day) are 6.7 and 10 times lower than the RfDs EPA used to develop its 2016 HAs and similar to those developed by New Jersey, though they are based on different studies and endpoints. View full publication

  • From the article:

    In an analysis of 309 women with heart disease who took hormone replacement therapy or placebo, Herrington found that women with a common mutation in the estrogen receptor alpha gene had dramatic increases in high-density lipoprotein (HDL), or the “good” cholesterol.

    “The increase in HDL was more than twice as much as in women without the gene variant,” said Herrington.

    […]

    Herrington found that 18 percent of women had a genetic predisposition to high levels of HDL cholesterol when taking estrogen. The HDL increase was dramatic – it was two or three times what is normally achieved with cholesterol drugs used to raise HDL.

    From the publication:

    Postmenopausal women with coronary disease who have the ER-α IVS1–401 C/C genotype, or several other closely related genotypes, have an augmented response of HDL cholesterol to hormone-replacement therapy.

    View full publication

  • From the article:

    Called the Estrogen in the Prevention of Atherosclerosis Trial (EPAT) the study monitored how much artery walls thickened over two years in 222 healthy postmenopausal women who took unopposed estrogen or a placebo.

    Women on estrogen therapy saw their atherosclerosis rate decrease by .0017 millimeters (mm) per year over two years, while artery wall thickness increased by .0036 mm per year over two years in women who took a placebo.

    As a guideline, Hodis says, an increase of .033 mm per year translates to a two-to-three-fold increase in risk of events such as heart attacks, and a starting thickness of .8 mm or greater also puts an individual at high risk.

    […]

    Also, EPAT investigators could compare women who used cholesterol-lowering drugs against women who did not take such medication. Besides taking estrogen or a placebo, all women who started the trial with levels of 160 or higher of low-density lipoprotein (often called LDL or “bad” cholesterol) were put on a cholesterol-lowering medication.

    Among the group of women who took no cholesterol-lowering medications in EPAT, those on estrogen therapy had .0147 mm per year slower atherosclerosis progression than those who took a placebo.

    Interestingly, women who received both estrogen and cholesterol-lowering drugs had about the same decrease in atherosclerosis progression as women who took cholesterol-lowering drugs alone.

    Researchers do not know why the combination of estrogen and cholesterol-lowering drugs does not result in even further atherosclerosis improvement. “But the effects of lipid-lowering drugs are quite powerful,” Hodis says. “You’re probably not seeing any effect above that.”

    View full publication

  • From the article:

    Dr. Ross Feldman, a clinical pharmacologist at London Health Sciences Centre and a scientist at the Schulich School of Medicine & Dentistry’s Robarts Research Institute, and his colleagues showed that the G-protein coupled estrogen receptor 30 (GPER) when activated by estrogen helps lower LDL cholesterol levels in the blood by inhibiting the protein PCSK-9.

    […]

    The study, which looked at two populations of women in northern Alberta and London, Ontario, also found that women who carry a common gene variant for GPER have a significant increase in LDL cholesterol levels. The gene variant, found in about 20 per cent of the population, impairs the ability of GPER to function and was shown in a previous study by the same authors to be associated with significant increases in blood pressure in women.

    View full publication

  • From the article:

    Using a variety of techniques to look directly at the tissue, the team saw that in APOE4 brains, aberrant amounts of cholesterol accumulated within cell bodies, especially of oligodendrocytes, but was relatively lacking around neural axons.

    To understand why, the team used patient-derived induced pluripotent stem cells to create lab cell cultures of oligodendrocytes engineered to differ only by whether they had APOE4 or APOE3. Again APOE4 cells showed major lipid disruptions. In particular, the afflicted oligodendrocytes hoarded extra cholesterol within their bodies, showed signs that the extra internal fats were stressing organelles called the endoplasmic reticulum that have a role in cholesterol transport, and indeed transported less cholesterol out to their membranes. Later, when they were co-cultured with neurons, the APOE4 oligodendrocytes failed to myelinate the neurons as well as APO3 cells did, regardless of whether the neurons carried APOE4 or APOE3.

    The team also observed that in postmortem brains there was less myelination in APOE4 carriers than APOE3 carriers.

    […]

    Eager to find a potential intervention, the team focused on drugs that affect cholesterol, including statins (which suppress synthesis) and cyclodextrin, which aids cholesterol transport. The statins didn’t help, but applying cyclodextrin to APOE4 oligodendrocyte cultured in a dish reduced accumulation of cholesterol within the cells and improved myelination in co-cultures with neurons. Moreover, it also had these effects in APOE4 mice.

    Finally, the team treated some APOE4 mice with cyclodextrin, left others untreated, and subjected them all to two different memory tests. The cyclodextrin-treated mice performed both tests significantly better, suggesting an association between improved myelination and improved cognition.

    Tsai said a clear picture is emerging in which intervening to correct specific lipid dysregulations by cell type could potentially help counteract APOE4’s contributions to Alzheimer’s pathology.

  • From the article:

    In the trial, participants who received higher doses of SLN360 – a small interfering RNA (siRNA) therapeutic that “silences” the gene responsible for lipoprotein(a) production – saw their lipoprotein(a) levels drop by as much as 96%-98%. Five months later, these participants' lipoprotein(a) – also known as Lp(a) – levels remained 71%-81% lower than baseline.

    […]

    Participants receiving 300 mg and 600 mg of SLN360 had a maximum of 96% and 98% reduction in Lp(a) levels, and a reduction of 71% and 81% at five months compared to baseline. Those receiving a placebo saw no change in Lp(a) levels. The highest doses also reduced LDL cholesterol by about 20%-25%.

  • From the article:

    Metabolic syndrome has emerged as a major public health concern, affecting 30% to 60% of postmenopausal women worldwide.

    […]

    The cross-sectional study included 616 postmenopausal women aged 49 to 86 years who were not taking estrogen and vitamin D/calcium supplements at the beginning of the trial. It concluded there was a positive correlation between vitamin D and estradiol.

    Specifically, higher vitamin D was associated with a favorable lipid profile, blood pressure, and glucose level. Estradiol was negatively associated with cholesterol, triglycerides, and blood pressure. These results suggest a synergistic role of vitamin D and estradiol deficiency in developing metabolic syndrome in postmenopausal women.

    View full publication

  • From the article:

    Marielle H. Emmelot-Vonk, M.D., of University Medical Center Utrecht, the Netherlands, and colleagues conducted a randomized, placebo-controlled study to assess the effects of testosterone supplementation on functional mobility, cognition, bone mineral density, body composition, lipids, quality of life, and safety parameters in older men with testosterone levels less than 13.7 nmol/L (less than the average level in this age group) during a period of six months. The trial, conducted from January 2004 to April 2005, included 207 men between the ages of 60 and 80 years. Participants were randomly assigned to receive 80 mg of testosterone undecenoate or a matching placebo twice daily for six months.

    The researchers found that during the study, lean body mass increased and fat mass decreased in the testosterone group compared with the placebo group but these factors were not accompanied by an increase of functional mobility or muscle strength. Cognitive function and bone mineral density did not change. Insulin sensitivity improved but high-density lipoprotein cholesterol (the “good” cholesterol) decreased. By the end of the study, 47.8 percent in the testosterone group vs. 35.5 percent in the placebo group had the metabolic syndrome (a strong risk factor for cardiovascular disease and type 2 diabetes, a group of several metabolic components in one individual including obesity and dyslipidemia). This difference was not statistically significant.

    Quality-of-life measures did not differ aside from hormone-related quality of life in the testosterone group. Adverse events were not significantly different in the two groups. Testosterone supplementation was associated with an increase in the concentrations of blood creatinine, a measure of kidney function, and hemoglobin and hematocrit, two red blood cell measures. No negative effects on prostate safety were detected (some reports have suggested that testosterone therapy could increase the risk of development or progression of prostate disease or cancer).

    View full publication

  • From the article:

    All 95 men in the studies (ages 34 to 69 years) had the metabolic syndrome. To receive this diagnosis, patients must have three of the following five risk factors: increased waist circumference (abdominal fat), low HDL (“good”) cholesterol, high triglycerides (fats in the blood), high blood pressure, and high blood sugar.

    The first study showed that testosterone treatment significantly reduced waist circumference, total cholesterol, LDL (“bad”) cholesterol, triglycerides, and body mass index (a measure of body fat). Treatment also increased “good” cholesterol. Improvements were progressive over 12 months, indicating that benefits may continue past a year, Saad said.

    In the second study, the researchers divided the patient population into three groups by age: less than 57 years, 57 to 63 years, and more than 63 years. They found that the oldest men had similar improvements in metabolic risk factors to the youngest men.

    Additionally, the investigators looked at the degree of testosterone deficiency before treatment. This beginning level of testosterone deficiency did not predict the beneficial outcome, they found. Men whose subnormal testosterone levels were not as low as the others had similar improvements in metabolic risk factors to men with the lowest levels, according to Saad.

    View full publication

  • From the aricle:

    Peterson and team then examined prevalence of nine chronic conditions, including type 2 diabetes, arthritis, cardiovascular disease, stroke, pulmonary disease, high triglycerides, hypercholesterolemia, hypertension and clinical depression.

    The researchers studied the prevalence of multimorbidity, or when two or more of the chronic conditions were present, among three age groups (young, middle-aged and older men) with and without testosterone deficiency. They found that low total testosterone [<300 ng/dL] was associated with multimorbidity in all age groups – but it was more prevalent among young and older men with testosterone deficiency.

    “We also found a large dose-response relationship between the age-specific low total testosterone and moderate total testosterone levels and multimorbidity, even after adjusting for obesity and muscle strength capacity,” Peterson says. “Which means that men should be concerned about declining total testosterone, even if it has not reached a level to warrant a clinical diagnosis (<300 ng/dL [10.4 nmol/L]).”

    View full publication

  • From the article:

    Niacin, or vitamin B3, is the one approved drug that elevates “good” cholesterol (high density lipoprotein, HDL) while depressing “bad” cholesterol (low density lipoprotein , LDL), and has thereby attracted much attention from patients and physicians. Niacin keeps fat from breaking down, and so obstructs the availability of LDL building blocks.

    Patients often stop taking niacin because it causes uncomfortable facial flushing, an effect caused by the release of a fat called prostaglandin or (PG)D2. PGD2 is the primary cause of the unwanted vasodilation, the “niacin flush.” The dilation occurs when blood vessels widen from relaxed smooth muscle cells within vessel walls.

    PGD2, formed by an enzyme called COX-2 and released by immune and skin cells, acts on a muscle cell-surface receptor called DP1 to cause the flushing.

    […]

    However, deletion of DP1 made mice somewhat more susceptible to hardening of the arteries, the formation of aneurysm, thrombosis, and in some cases, high blood pressure. The researchers suggest that these findings are reflective of DP1 expression in vascular and immune cells in mice, just as in humans, despite its absence on mouse platelet cells.

    View full publication

  • From the article:

    • If smoking women with high systolic blood pressure values have 20 times higher rate of these brain bleeds than never-smoking men with low blood pressure values, it may very well be that these women diagnosed with unruptured intracranial aneurysms should be treated. On the other hand, never-smoking men with low blood pressure values and intracranial aneurysms may not need to be treated at all.

    In this largest SAH risk factor study ever, the study group also identified three new risk factors for SAH: previous myocardial infarction, history of stroke in mother, and elevated cholesterol levels in men. The results revise the understanding of the epidemiology of SAH and indicate that the risk factors for SAH appear to be similar to those for other cardiovascular diseases.

    • We have previously shown that lifestyle risk factors affect significantly the life expectancy of SAH survivors, and now we have shown that the same risk factors also affect dramatically the risk of SAH itself.

    View publication

  • From the article:

    The study found the lifetime risk of an abdominal aortic aneurysm were: 1 in 17 among all study participants; 1 in 9 among current smokers; 1 in 9 among those in the top third of smoking pack-years (number of cigarettes smoked over a lifetime), whether a current or former smoker; 1 in 12 among current female smokers.

    Researchers also found those who had quit smoking for 3-8 years (recent quitters) still had an approximately 2.6 to 3.5 fold increased risk for both clinical and asymptomatic abdominal aortic aneurysm in the next 15 years compared to never smokers. Their lifetime risk was 6.6 percent higher than long-term quitters.

    For women, authors note the steep increase in risk is particularly concerning given the United States Preventive Services Task Force recommends that current or former male smokers undergo an ultrasound screening for an abdominal aortic aneurysm once between the ages of 65 and 75 but makes no such recommendation for women.

    […]

    The study also found that being older, white, or having high levels of bad cholesterol also increased the risk of abdominal aortic aneurysm.

    View full publication

  • Dietary fiber improves symptoms of metabolic syndrome.

    Metabolic syndrome is a constellation of medical conditions that includes high blood pressure, high blood glucose, unhealthy cholesterol levels, and excess abdominal fat. Having metabolic syndrome increases a person’s risk of heart disease, stroke, and diabetes. A 2009 study found that supplemental psyllium and guar gum improved symptoms associated with metabolic syndrome.

    Psyllium, found in husks of the psyllium (Plantago ovata) seed, and guar gum, found in guar beans and commonly used as a food additive, are types of soluble dietary fiber. Soluble fibers dissolve in water and pass intact into the large intestine, where they are converted by colonic bacteria to prebiotic gels. Evidence indicates that consumption of soluble dietary fibers is associated with improved metabolic function, cardiovascular health, and gut function.

    The six-month study involved 141 adults (average age, ~58 years) who had metabolic syndrome. The investigators randomly assigned participants to one of three groups. One group consumed supplemental psyllium husk powder twice a day before meals, while the other consumed guar gum. The third group consumed a standard diet. Investigators measured the participants' metabolic markers, blood lipids, blood pressure, and body weight before and after the intervention.

    Participants who consumed the psyllium and guar gum exhibited reduced blood glucose, insulin, low-density lipoprotein cholesterol, and apolipoprotein B (a component of very-low-density lipoprotein), compared to their baseline levels. Those who took the psyllium showed marked improvements in their triglycerides (~13 percent lower) and blood pressures (systolic, ~4 percent lower; diastolic, ~3 percent lower). Those who took the guar gum lost slightly more weight than those who took the psyllium. Participants who followed the standard diet did not exhibit significant improvements in any measures.

    These findings suggest that soluble dietary fibers such as psyllium and guar gum reduce weight and improve markers of metabolic health in people with metabolic syndrome. Dietary fibers also maintain gut barrier function, which is often impaired in metabolic syndrome due to increased intestinal permeability. Learn more about intestinal permeability in our overview article.

  • Anthocyanins reduce cholesterol and triglyceride levels.

    Anthocyanins are blue- and purple-colored polyphenolic compounds found in fruits and vegetables, including blueberries, raspberries, eggplants, and others. Robust evidence indicates that anthocyanins exert antioxidant, anti-inflammatory, and/or neuroprotective effects and may reduce a person’s risk of developing cardiovascular disease, cancer, and type 2 diabetes. Findings from a recent meta-analysis found that anthocyanins reduce cholesterol and triglyceride levels in people with dyslipidemia.

    Dyslipidemia is an abnormal condition in which levels of blood lipids, such as cholesterol or triglycerides, are too high or too low. Dyslipidemia can be caused by genetic or lifestyle factors and may increase a person’s risk of developing atherosclerosis, a condition characterized by high levels of triglycerides and small, dense low-density lipoprotein (LDL) particles, and low levels of high-density lipoprotein (HDL) cholesterol.

    The investigators conducted a meta-analysis, a type of study that analyzes the data derived from multiple studies using objective, statistical formulas to identify a common effect. Their analysis only included randomized, placebo-controlled trials in adults that examined links between anthocyanin supplementation and total cholesterol, triglyceride, LDL, and HDL levels (measured in milligrams per deciliter [mg/dL]). Six studies, involving nearly 600 participants, met their criteria.

    They found that anthocyanin supplementation had favorable effects on total cholesterol (24.06 mg/dL decrease), triglycerides (26.14 mg/dL decrease), LDL (22.10 mg/dL decrease) and HDL (5.58 mg/dL increase). These effects were observed even when considering the participants' age, body mass index, anthocyanin dose, duration of intervention, and ethnicity.

    These findings suggest that anthocyanins, a class of polyphenols, markedly improve blood lipid concentrations. They also underscore the value of dietary measures in managing dyslipidemia. Learn more about polyphenols in our overview article.

  • Lycopene, the red pigment in tomatoes and watermelon, reduces cholesterol levels and improves blood pressure.

    Lycopene is a naturally occurring antioxidant compound that gives tomatoes, watermelon, and other red or pink fruits and vegetables their characteristic colors. Evidence suggests that lycopene intake reduces the risk of cardiovascular disease and provides protection against prostate cancer. A 2010 meta-analysis found that lycopene reduces cholesterol levels and improves blood pressure.

    High cholesterol levels and elevated blood pressure often go hand-in-hand and are among the primary contributors to cardiovascular disease and stroke risk. Although a vast array of drugs is available for the treatment of high cholesterol and blood pressure, many of these drugs carry unwanted side effects and risks, including an increased risk for type 2 diabetes and certain types of cancer

    The investigators conducted a meta-analysis, a type of study that analyzes data from several studies using objective, statistical formulas to identify a common effect. Their analysis included studies that examined the effects of lycopene on cholesterol or blood pressure for at least two weeks' duration. They also investigated whether dose influenced the effects of lycopene on cholesterol and whether the participants' baseline blood pressure influenced the response to lycopene.

    They identified 12 studies that investigated the effects of lycopene on cholesterol and four that investigated its effects on blood pressure. Lycopene doses used in the various studies ranged from 4 to 44 milligrams per day. Study durations typically lasted two to six weeks, but one trial lasted six months. They found that doses of at least 25 milligrams per day (roughly the amount in one-half cup of sundried tomatoes) reduced low-density lipoprotein cholesterol (LDL) by about 10 percent, comparable to the effects of a low-dose statin, a commonly used class of cholesterol-lowering drugs. They also found that lycopene reduced systolic blood pressure by approximately 5 mmHg. This effect was observed in participants who had high blood pressure but not in those whose blood pressure was normal.

    These findings suggest that lycopene reduces cholesterol and blood pressure. They also underscore the usefulness of implementing dietary approaches to treat these common conditions.

  • Abstract

    “Cerebrovascular endothelial cells (CEC) comprise the blood-brain barrier (BBB). In a previous study, we showed that oxidized LDL (oxLDL) can induce apoptosis of mouse CEC. Resveratrol possesses chemopreventive potential. This study aimed to evaluate the effects of resveratrol on oxLDL-induced insults to mouse CEC and its possible mechanisms. Exposure of mouse CEC to 200 μmol/L oxLDL for 1 h did not cause cell death but significantly altered the permeability and transendothelial electrical resistance of the cell monolayer. However, resveratrol completely normalized such injury. As for the mechanisms, resveratrol completely protected oxLDL-induced disruption of F-actin and microtubule cytoskeletons as well as occludin and zona occludens-1 (ZO-1) tight junctions. The oxLDL-induced decreases in the mitochondrial membrane potential and intracellular ATP levels were normalized by resveratrol. Exposure of mouse CEC to 200 μmol/L oxLDL for 24 h elevated oxidative stress and simultaneously induced cell apoptosis. However, resveratrol partially protected against oxLDL-induced CEC apoptosis. The oxLDL-induced alterations in levels of Bcl-2, Bax, and cytochrome c were completely normalized by resveratrol. Consequently, resveratrol partially decreased oxLDL-induced activation of caspases-9 and -3. Therefore, in this study, we show that resveratrol can protect against oxLDL-induced damage of the BBB through protecting disruption of the tight junction structure and apoptotic insults to CEC.”

  • Since the 1980’s, clinicians and researchers have been puzzled by the “French paradox”: the observation that residents of France have a surprisingly low incidence of cardiovascular disease given their high rates of smoking, intakes of saturated fat, and hypercholesterolemia (i.e. abnormally high serum levels of harmful low-density lipoprotein (LDL) cholesterol). A recent study now offers evidence that the negative health impacts of these common risk factors might be effectively mitigated by the French habit of regular red wine consumption.

    The authors of this study examined mice that had been genetically modified to lack LDL receptors – proteins crucial for removing LDLs from the bloodstream and initiating their degradation. This genetic modification, known as a “knock-out”, meant that the mice experienced a virtually life-long state of hypercholesterolemia, which served as the biological backdrop for an experiment on the potential health effects of wine consumption.

    At the age of three months (early mouse adulthood), animals were randomly assigned to receive 60 days of unlimited access to either plain tap water or red wine diluted to yield a 6% ethanol solution. This concentration ensured that the animals consumed the human equivalent of a 5-ounce glass of wine on a daily basis.

    When the researchers tested the mice on a variety of cognitive tasks, they discovered that the water-only group displayed learning and memory impairments characteristic of their poor lipid profiles. Their performance was particularly poor on a short-term memory test, where the animals turned out to be unable to recognize objects they had seen only an hour prior. Long-term memory retention was also compromised. In a test that required the animals to remember the location of an escape platform hidden in a tub of opaque water, the mice swam in the right direction only 20 percent of the time.

    Interestingly, wine-consuming mice were not impaired to the same degree. And while their plasma lipid profiles were no better compared to their water-drinking peers, they had substantially lower levels of several biomarkers of neuroinflammation, such as GFAP and lectin. The findings indicate that red wine compounds might help protect against the negative health outcomes of hypercholesterolemia by interfering with the associated inflammatory processes.

    Link to full study.

  • From the article:

    The study recruited 125 amateur cyclists aged 55 to 79, 84 of which were male and 41 were female. The men had to be able to cycle 100 km in under 6.5 hours, while the women had to be able to cycle 60 km in 5.5 hours.

    […]

    The cyclists also did not increase their body fat or cholesterol levels with age and the men’s testosterone levels also remained high, suggesting that they may have avoided most of the male menopause.

    More surprisingly, the study also revealed that the benefits of exercise extend beyond muscle as the cyclists also had an immune system that did not seem to have aged either.

    An organ called the thymus, which makes immune cells called T cells, starts to shrink from the age of 20 and makes less T cells. In this study, however, the cyclists' thymuses were making as many T cells as those of a young person.

  • A Western diet pattern, characterized by a low intake of fruits and vegetables and a high intake of sugar and processed foods, promotes the development of obesity and metabolic disease. Time restricted eating has been shown to decrease weight and improve metabolic health in humans. However, factors such as age and sex modulate both susceptibilty to obesity and likelihood of responding to weight-loss treatments. Authors of a new report found that male mice experienced greater metabolic benefit from time-restricted feeding than females.

    Time-restricted eating, the practice of limiting food intake to an 8- or 12-hour window, is an emerging therapy for the treatment and prevention of metabolic diseases. Much of the research about time-restricted eating in humans is based on research of time-restricted feeding in mice, which has elucidated many of the cellular mechanisms related to [time-restricted eating’s benefits.](​​https://journals.physiology.org/doi/full/10.1152/ajpregu.00775.2005) These two terms distinguish which population, humans or non-human animals, is practicing time-restricted food intake.

    The prevalence of obesity is on the rise in the industrialized world, a problem compounded by an increasing average age in the same populations. The accumulation of extra fat throughout life puts a person at greater risk of metabolic disease as they age. Females are more likely to gain and retain fat mass than males; however, pre-menopausal females tend to have lower rates of type 2 diabetes and cardiovascular disease due to the protective effects of estrogen. Previous research in humans has demonstrated weight loss and improved metabolic health with time-restricted eating; however, additional research is needed to understand the sex- and age-dependent effects of time-restricted eating.

    The researchers used male and female mice of two ages: three months old (equivalent to 20-year-old humans) and 12 months old (equivalent to 42 year-old-humans). They fed mice a chow diet representative of a Western diet pattern with 17 percent of calories from sugar (human equivalent of about 25 ounces of soda per day) and 45 percent of calories from fat including lard and soybean oil. Current dietary guidelines recommend limiting solid fats such as lard). Half of the mice had 24-hour access to food while the other half only had restricted access, limited to just nine hours per day. Mice continued their diet for a total of 12 to 13 weeks. After 10 weeks, the researchers measured changes in the animals' body weight, glucose sensitivity, serum cholesterol, fatty liver, muscle performance, and immune response when challenged with bacterial endotoxin.

    Although mice in the time-restricted feeding group consumed the same amount of food as mice with constant access to food, time-restricted feeding resulted in 15 percent less weight gain in young male mice and 23 percent less weight gain in older male mice. Time-restricted feeding did not significantly prevent weight gain in female mice. Male mice also experienced a greater reduction in serum cholesterol with time-restricted feeding compared to females. Both older male and female mice had lower rates of insulin resistance and fatty liver while on time-restricted feeding. This protection was likely due to changes in gene expression that increased glucose uptake by and decreased glucose output from the liver. In young male mice, time-restricted feeding preserved muscle mass, function, and performance, but not in young females. Finally, when challenged with bacterial endotoxin, older mice practicing time-restricted feeding were significantly more likely to survive septic shock than mice with 24-hour access to food, demonstrating better health and resilience.

    Time-restricted feeding improved survival of septic shock and provided protection against insulin resistance and fatty liver in both sexes; however, male mice experienced greater reductions in body weight and serum cholesterol and maintained greater muscle mass and performance compared to female mice. The authors noted that their research is of particular interest considering the increased risk of severe COVID-19 illness in those with poor metabolic health.

  • Not sure what to think of this. At this point my main reason for believing the cholesterol (or apoB) hypothesis are the genetic results showing 88% reduction of CVD rates among pcsk9- people (or actually, they would be pcsk9-/+ heterozygotes, given how rare the allele is) in the ARIC study:

    https://www.ncbi.nlm.nih.gov/pubmed/24518357

    That, if I’m being honest, and Thomas Dayspring’s anecdote about the terrible MI epidemic he dealt with as a resident (or was he an intern?) and the dramatic decline in such events after the advent of statins. He regaled us with this story during Peter Attia’s “Week of Dayspring” Drive Podcast:

    https://peterattiamd.com/tomdayspring1/

    And, I suppose @rhonda either your podcast or Attia’s podcast interview of Ron Krauss: https://www.foundmyfitness.com/episodes/ronald-krauss https://peterattiamd.com/ronkrauss/

    Where Krauss mentions almost off-hand being an author on a review paper pointing out the CHD effects of higher LCL-P levels and saying “which I would not have thought necessary” – meaning the case had been so thoroughly proven there was little point even undertaking the task.

  • FTA

    … a clinical trial in 60 overweight (BMI > 25), healthy adults, aged 40-60 years. After initial screening, the subjects were randomized into four groups with 15 per group. The four groups received, respectively, placebo, omega-3 fatty acid, probiotic VSL#3, or both omega-3 and probiotic, for 6 weeks. […] The probiotic (VSL#3) supplemented group had a significant reduction in total cholesterol, triglyceride, LDL, and VLDL and had increased HDL (P < 0.05) value. VSL#3 improved insulin sensitivity (P < 0.01), decreased hsCRP and favorably affected the composition of gut microbiota. Omega-3 had a significant effect on insulin sensitivity and hsCRP but had no effect on gut microbiota. The addition of omega-3 fatty acid with VSL#3 had a more pronounced effect on HDL, insulin sensitivity and hsCRP. Table showing statistics of the study.