Fatty Liver
Episodes
Dr. Guido Kroemer discusses immunology, cancer biology, calorie-restriction mimetics, aging, and autophagy.
Dr. Satchin Panda discusses the roles that fasting, time-restricted eating, and circadian rhythms play in human health.
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Aging Nutrition Cancer Podcast Fasting Multiple Sclerosis Autophagy Video Triglycerides Fatty Liver Time-Restricted Eating ProteinDr. Guido Kroemer discusses immunology, cancer biology, calorie-restriction mimetics, aging, and autophagy.
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Dr. Satchin Panda discusses the roles that fasting, time-restricted eating, and circadian rhythms play in human health.
Topic Pages
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Berberine
Berberine activates AMPK and suppresses SREBP-1c-mediated lipogenesis, enhancing β-oxidation to alleviate nonalcoholic fatty liver.
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Ultra-processed Foods (UPFs)
Ultra-processed foods promote hepatic de novo lipogenesis, insulin resistance, and inflammation, mechanistically precipitating non-alcoholic fatty liver.
News & Publications
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Long-term intervention with calorie restriction and high-intensity interval training doubles insulin sensitivity and greatly improves liver function in people with a form of fatty liver disease. pubmed.ncbi.nlm.nih.gov
Metabolic dysfunction-associated steatohepatitis (MASH) is a form of fatty liver disease that promotes inflammation and damage over time. Closely connected to conditions like obesity and insulin resistance, MASH affects nearly one-third of people worldwide. A recent study found that a long-term intervention combining calorie restriction and high-intensity interval training (HIIT) in people with MASH improved liver function, doubling insulin sensitivity.
Researchers assigned people with MASH to either a treatment group (16 participants) that received lifestyle counseling and exercise training or a control group (eight participants) that continued with standard medical care. The treatment group engaged in supervised HIIT three times a week while reducing caloric intake. The researchers assessed the participants' liver fat, measured blood biochemistries, and evaluated insulin sensitivity before and after the intervention.
They found that the treatment group experienced notable reductions in body weight, fat mass, and liver injury. Their cardiorespiratory fitness improved considerably, and they exhibited a twofold increase in peripheral insulin sensitivity compared to the control group. Both groups saw reductions in total energy intake and liver fat.
These findings suggest that combining caloric restriction with regular high-intensity exercise can yield marked improvements in liver health and insulin sensitivity, likely by redistributing excess nutrients to skeletal muscle. Learn more about calorie restriction in this clip featuring Dr. David Sinclair, and HIIT in this clip featuring Dr. Martin Gibala.
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Flavonoid supplementation emerges as a promising treatment for non-alcoholic fatty liver disease. onlinelibrary.wiley.com
Non-alcoholic fatty liver disease, or NAFLD, causes fat accumulation in the liver, inflammation, and insulin resistance. It’s the most common chronic liver condition among people in the United States, affecting roughly 90 percent of people with obesity, or about 38 percent of the overall population. A recent systematic review and meta-analysis found that flavonoid supplementation reduces the risk of developing NAFLD.
Researchers reviewed the findings of 12 randomized controlled trials investigating the effects of flavonoid supplementation in people with NAFLD. They found that flavonoid supplementation improved markers of liver function (liver enzymes) and reduced blood lipids (triglycerides and cholesterol), inflammatory markers (TNF-alpha and NF-kappa B), and fat accumulation in the liver, suggesting that flavonoid supplementation is a viable option for managing and treating NAFLD.
Flavonoids are bioactive compounds found in many fruits and vegetables. Evidence suggests they exert a wide range of beneficial effects in humans, including anti-inflammatory, antioxidant, and lipid-lowering activities, as well as counteracting insulin resistance. Higher flavonoid intake is associated with a lower risk of NAFLD progression in older adults with overweight or obesity.
Evidence suggests sulforaphane, a bioactive compound derived from broccoli, also benefits liver health. Learn more about sulforaphane in our comprehensive overview article.
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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.
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Fructose-containing beverages increase free fatty acid production in the liver, a marker of metabolic disease risk. www.sciencedaily.com
Metabolic diseases, such as type 2 diabetes, cardiovascular disease, and non-alcoholic fatty liver disease (NAFLD), represent a major public health burden. Dietary factors such as excess sugar intake are associated with greater metabolic disease risk; however, it is unclear how different types of sugars (e.g., glucose, fructose, or sucrose) differentially impact metabolic health. In this report, researchers investigated the effects of sugar-sweetened beverages on fatty acid synthesis, blood triglycerides, and hepatic insulin resistance in healthy males.
Following the consumption of glucose, the pancreas secretes insulin into the bloodstream so that insulin-sensitive organs such as the liver, skeletal muscle, and adipose tissue can transport glucose into their cells. Excess sugars are converted to fats in the liver via a process called de novo lipogenesis and then stored in adipose tissue; however, as fat levels in adipose tissue rise (i.e., overweight and obesity), fat accumulates in the liver leading to the development of NAFLD. Fructose, the main sweetener found in sugar-sweetened beverages, does not require insulin to be absorbed and is preferentially taken up by the liver, accelerating NAFLD development independent of weight gain.
The authors recruited 94 healthy lean males (average age, 23 years) and assigned them to consume beverages sweetened with moderate amounts of either glucose, fructose, or sucrose (a sugar that contains both glucose and fructose) in addition to their normal diet for seven weeks. The beverages contained an amount of sugar found in about two cans of non-diet soda. The researchers assigned a fourth group of participants to consume their normal diet with no added sugar-sweetened beverages. They assessed fatty acid and triglyceride synthesis by the liver and whole-body fat metabolism.
Daily consumption of beverages sweetened with fructose and sucrose, but not glucose, led to a twofold increase in the production of free fatty acids in the liver. Fructose intake did not increase triglyceride production in the liver or whole-body fat metabolism. Participants from all four groups consumed about the same amount of calories, and while body weight tended to increase for all groups, this relationship was only statistically significant for the group consuming glucose-sweetened beverages. Glucose and insulin tolerance did not change with sugar-sweetened beverage consumption.
The investigators concluded that consumption of beverages sweetened with fructose and sucrose increased free fatty acid production in the liver. While they did not observe changes in other metabolic markers such as insulin tolerance, they hypothesized that the alterations in fat production by the liver pave the way for metabolic disease development.
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As a cofactor in the biosynthesis of carnitine, vitamin C may have a role in enhancing PPAR-alpha-dependent fatty acid oxidation www.nature.com
From the publication:
Ascorbic acid is a known cofactor in the biosynthesis of carnitine, a molecule that has an obligatory role in fatty acid oxidation […] Ascorbic acid supplementation increased the mRNA levels of PPARα and its target enzymes involved in fatty acid β-oxidation in visceral adipose tissues. Consistent with the effects of ascorbic acid on visceral obesity, ascorbic acid not only inhibited hepatic steatosis but also increased the mRNA levels of PPARα-dependent fatty acid β-oxidation genes in livers. Similarly, hepatic inflammation, fibrosis, and apoptosis were also decreased during ascorbic acid-induced inhibition of visceral obesity. In addition, serum levels of alanine aminotransferase, aspartate aminotransferase, total cholesterol, and LDL cholesterol were lower in HFD-AA-fed mice than in those of HFD-fed mice.
A few bullet points:
- Reduced visceral obesity
- Reduced hepatic inflammation
- Increased expression of PPAR-a
- Improved markers of liver health and cholesterol
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Low maternal vitamin D levels in early to mid-pregnancy were associated with an increased risk for offspring ADHD. www.sciencedaily.com
Attention deficit hyperactivity disorder (ADHD) is a developmental disorder characterized by poor focus, hyperactivity, and impulsive behavior. Approximately 5 percent of all children worldwide have ADHD. Findings from a recent study suggest that poor maternal vitamin D status may play a role in the pathophysiology of ADHD in children.
Vitamin D is a fat-soluble vitamin stored in the liver and fatty tissues. It plays key roles in several physiological processes, such as the regulation of blood pressure, calcium homeostasis, immune function, and the regulation of cell growth. Emerging evidence indicates that vitamin D is critical for the health and function of the central nervous system. Vitamin D is synthesized in a multistep process in the skin, liver, and kidneys following exposure to ultraviolet light or it can be obtained from dietary sources such as salmon, mushrooms, and many fortified foods.
The National Academy of Medicine (formerly the Institute of Medicine, IOM) has determined that people are at risk for vitamin D deficiency if their levels are less than 30 nmol/L, and are potentially at risk for deficiency if their levels are between 30 and 50 nmol/L. Levels of 50 nmol/L are considered sufficient for most people.
The population-based case-control study included 1,067 children born in Finland between 1998 and 1999 who had been diagnosed with ADHD and 1,067 matched controls. The study drew on data from Finnish national registries as well as maternal blood samples collected during the first trimester of pregnancy for women enrolled in the Finnish Maternal Cohort of the Northern Finland Biobank Borealis. These samples were collected before Finland began recommending vitamin D supplementation during pregnancy.
The data were adjusted for several potential confounding factors, including the number of previous births, maternal socioeconomic status, maternal age, self-reported smoking during pregnancy, maternal cotinine levels (a biomarker of nicotine), gestational age, weight for gestational age, information on maternal and paternal psychiatric diagnoses (including ADHD), substance use disorders, maternal immigrant background, and month of blood draw.
The study revealed that children born to women who had low vitamin D status during their pregnancies were 45 percent more likely to develop ADHD, even after adjusting for maternal socioeconomic status and age. The average vitamin D level among women whose children developed ADHD was 29 nmol/L.
There are biologically plausible explanations for the association between developmental vitamin D deficiency and an increased risk of offspring ADHD. Early pregnancy is a critical period for fetal brain development, which is a complex process influenced by genetics and the in utero environment.
I published an article a few years ago first identifying how vitamin D regulates the conversion of the essential amino acid tryptophan into serotonin, and how this may influence the development of neurodevelopmental disorders such as autism spectrum disorder, ADHD, bipolar disorder, and schizophrenia, which all share as a unifying attribute low brain serotonin. Read more about these findings here.
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Gut bacteria may alter the aging process of the human brain through the production of butyrate www.sciencedaily.com
The gut microbiota is a complex and dynamic population of microorganisms that is subject to change throughout an individual’s lifespan in response to the aging process. Findings from a new study demonstrate that altering the gut microbial population may alter the aging process of the human brain.
The authors of the study transplanted gut microbiota samples from healthy young or old mice into young germ-free mice. Eight weeks after the transplant, the mice that received microbial samples from the old mice demonstrated increased neurogenesis – the process of forming new neurons – in the hippocampus region of their brains.
Further analysis revealed that these mice also had larger numbers of butyrate-producing microbes in their colons. Butyrate, a short-chain fatty acid, is produced during bacterial fermentation in the human colon and has wide-ranging effects on human physiology. In this study, butyrate was associated with an increase in growth factors and subsequent activation of key longevity signaling pathways in the livers of the recipient mice. When butyrate alone was given to the recipient mice it promoted neurogenesis, as well.
The findings from this study may have relevance for dietary interventions to maintain or improve brain health.
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Low-density lipoproteins (LDL) are formed in the liver and transport lipid molecules to cells. Often referred to as the “bad cholesterol,” LDL can drive cardiovascular disease if it becomes oxidized within the walls of arteries. LDL particles exist in different sizes, ranging from large, “fluffy” molecules to small, dense molecules. Scientific evidence suggests that small, dense LDL particles are more susceptible to oxidative modification. Findings from a new study suggest that diets that include avocados may help reduce LDL oxidation.
The randomized, controlled trial involved 45 men and women between the ages of 21 and 70 years. The participants, who were overweight or obese and had elevated LDL cholesterol levels, followed three different diets for a period of five weeks each: a low-fat diet, a medium-fat diet with avocado, and a medium-fat diet with oleic acids (found in olive and canola oils).
Avocados are rich sources of monounsaturated fatty acids. They also contain polyphenols and lutein, a carotenoid compound that quenches and scavenges reactive oxygen species.
After five weeks on the diet with avocado, the participants' levels of oxidized LDL cholesterol (especially the small, dense LDL cholesterol particles) were lower than their baseline levels or after completing the low- or moderate-fat diets. Concentrations of large, fluffy LDL particles were unchanged. Participants also had higher levels of lutein. These findings suggest that consuming avocados as part of an overall heart-healthy diet may reduce the risk of developing cardiovascular disease.
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Sulforaphane (found in broccoli sprouts) causes 20% fat loss by changing gut bacteria & increasing mitochondria in fat in mice. www.sciencedaily.comGut Obesity Microbiome Metabolism Inflammation Sulforaphane Fatty Liver NRF2 Endotoxemia Lipopolysaccharide Visceral Fat
Sulforaphane from broccoli sprouts causes 20% visceral fat loss by changing gut bacteria and increasing mitochondria in fat in mice. The mice fed sulforaphane also lowered fatty liver and reduced blood glucose levels. Sulforaphane reduced inflammation by decreasing a species of bacteria in the gut that is responsible for producing endotoxin, which is a major source of inflammation. Also, sulforaphane increased the levels of UCP1, which is responsible for increasing mitochondrial biogenesis (the generation of new mitochondria) in fat (called browning of fat). The browning of fat increases fat metabolism and can lead to fat loss. There have been human studies showing that sulforaphane decreases inflammatory biomarkers and improves blood glucose levels. It will be interesting to see future studies looking at these two new functions of sulforaphane in humans. For more information check out my video on sulforaphane or my podcast with Dr. Jed Fahey, who discovered broccoli sprouts are the best source of sulforaphane. Sulforaphane video: https://youtu.be/zz4YVJ4aRfg Sulforaphane podcast: https://youtu.be/Q0lBVCpq8jc
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[TIMELINE] Joe Rogan Experience #502 with Dr. Rhonda Patrick www.foundmyfitness.comOmega-3 Depression Insulin Fatty Liver Vitamin A Isothiocyanates Antioxidant Protein Dairy Blood Sugar Metabolic Syndrome Myrosinase
This is the full minute-by-minute timeline for JRE #502. Click here to watch the video on YouTube.
- 00:02:42 - Starts off by talking about kappa opioids and dynorphin and how you feel stress right before important events
- 00:04:24 - Joe talks about how great you feel after a competition (fight)
- 00:05:35 - Talks about how capsaicin in spicy food also induces a release of endorphins via dynorphin agonization
- 00:06:22 - Briefly mentions sauna/hyperthermic conditioning article featured on 4-Hour Workweek
- 00:06:45 - Description of hormesis and how this is part of the mechanism of action for things like EGCGs in green tea and polyphenols in fruit.
- 00:07:50 - Joe brings up that Rhonda suggested mycotoxin might be hormetic previously, Rhonda clarifies this was entirely and highly speculative. Includes jazz hands.
- 00:08:45 - Joe mentions that his best decisions are made after a good workout. He does not trust his judgment if he has not got a good workout in.
- 00:09:15 - Discussion of exercise and how it grows new brain cells (neurogenesis) via the BDNF pathway and how the growth of new brain cells allows you to forget other memories.
- 00:11:20 - Joe mentions how people in highschool that never left your small hometown sometimes remember stuff you don’t. Get out of the small town, highschool friends. Make new memories.
- 00:12:00 - Talks about how amygdala activation from either extreme excitement or fear increases episodic memory.
- 00:12:15 - Talks about her new paper and how serotonin plays a role in brain function/dysfunction, behavior, and episodic memory.
- 00:13:38 - Joe brings up MDMA burnout and suggests serotonin’s role in episodic memory may be why the MDMA/roller burnout stereotype exists
- 00:15:00 - Explanation of what receptor down-regulation is and why it adds enormous complexity to understanding the effects of drugs, like SSRIs.
- 00:16:27 - Discussion of “Serotonin Syndrome.”
- 00:17:22 - Most serotonin is actually made in the gut, not the brain.
- 00:17:44 - Discussion of how the genes that convert tryptophan to serotonin found in the gut (TPH1) and in the brain (TPH2) are show a characteristic nucleotide sequence known as a “Vitamin D Response Element” that seems to indicate, for the most part, that Vitamin D represses the production of serotonin in the gut (TPH1) and increases serotonin in the brain (TPH2). This is the subject of Rhonda’s most recent academic paper: “Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism.”
- 00:18:45 - Serotonin made in the gut has been shown to cause gastrointestinal inflammation by activating T cells and causing them to proliferate. Knocking out TPH1 in a mouse model of colitis ameliorates the inflammation associated with the disorder.
- 00:21:55 - Theoretical vitamin D mechanism may play a role in the development of autism by depriving developing foetus of serotonin that serves as an “early brain morphogen” when mothers are deficient in vitamin D.
- 00:23:45 - Autism appears to be developing early in utero (during pregnancy) and seems to show indications of being at least partially related to environment.
- 00:24:00 - Estrogen can activate TPH2 in lieu of Vitamin D and thus may explain why autism is predominantly found in males.
- 00:24:30 - Gut inflammation is common among autistics.
- 00:24:45 - Explains 5-HTP bypasses the normal tryptophan hydroxylase (TPH) conversion, and because of that it can be converted into serotonin more rapidly… but (hypothetically) too soon and in the gut instead of the brain.
- 00:25:35 - Tryptophan gets transported into the brain in order to be converted into serotonin by tryptophan hydroxylase (TPH2) but competes with BCAAs for transport into the brain, which are transported preferentially.
- 00:25:55 - Tryptophan is less abundant of an amino acid than branch chain amino acids like leucine in protein.
- 00:26:55 - Joe asks Rhonda if T cell activation/proliferation in the context of TPH1 has relevance for AIDS.
- 00:28:00 - Joe relates how “New Mood” (Onnit’s product) was originally called “Roll Off.”
- 00:30:30 - Joe quips that it was recently experimentally validated in mice that DMT is produced in the pineal glands of mice during sleep, goes on to talk about speculation that near death experiences relating to altered perception from endogenous DMT release.
- 00:35:10 - Plays a video of a jaguar eating hallucinogenic plants.
- 00:37:20 - Talks about monoamine oxidase
- 00:38:40 - Merits of “theoretical papers” (like “Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism.”)
- 00:39:37 - 70% of population is vitamin d deficient. Segways to awesome infographic created by @tjasonwright which covers a ton of the basic facts about vitamin D.
- 00:43:02 - BaadBobby’s Dad turned Joe onto TA-65. TA-65 has been shown to increase telomere length, but theres a guy who sued the company producing it. Anecdotally, BaadBobby’s dad had improvements in eyesight.
- 00:45:00 - Explanation of what telomeres are.
- 00:48:50 - Special enzyme telomerase rebuilds telomeres, but it’s found mostly only in stem cells… and more importantly: cancer cells. Cancer cells hijack this telomerase normally reserved for stem cells to live forever. Strangely… Mice, unlike humans, actually express telomerase in all of their cells and don’t have telomere shortening.
- 00:50:10 - Werner’s syndrome involves excessive telomere shortening.
- 00:53:33 - Explains how aging is a function of DNA damage and discusses DNA damage assay (test) that Rhonda performs.
- 00:55:30 - Obesity link to increased DNA damage.
- 00:56:50 - Talks about TA-65’s active ingredient in a study was shown to genuinely increase telomerase activity and length of telomeres.
- 00:58:22 - TA-65 study showed a 40% increase in telomere length in white blood cells in some humans studied.
- 00:58:44 - Second study on TA-65 using special mouse model from well-known lab also showed re-activation of telomerase, and even began reversing aging of their tissues. Mice notably did not get cancer. Reinforces findings of first study.
- 01:01:30 - Still concerned TA-65 could encourage the growth of pre-cancerous cells.
- 01:02:00 - Joe brings up alkalizing diet for cancer prevention (he’s a skeptic).
- 01:03:05 - Bad bacteria in gut is affected by pH.
- 01:06:20 - Joe brings up argument that sugar consumption affects growth of cancer.
- 01:07:50 - Explains because cancer cells become glycolytic which is why people fixate on sugar as a potential cancer cell.
- 01:08:40 - Rhonda mentions that taking away glucose, but allowing continued presence of glutamine allowed cancer cells to keep growing in vitro.
- 01:09:50 - Folic acid needed in the absence of cancer because you need it to build new DNA – but this is a problem if you do have a cancer because it can be a bad thing for the same reasons (folic acid needs to produce DNA because cancer cells are highly proliferative).
- 01:12:00 - Glucosinolates are cleaved into isothiocyanates by myrosinase which is de-activated by heat. Isothiocyanates are potent anti-cancer agents. Recent anti-kale stuff is, in a way, anti-isothiocyanates. Additionally, if you boil kale and de-activate myrosinase you’re actually decreasing the amount of isothiocynates by removing myrosinase.
- 01:14:00 - Kale thyroid stuff is probably only relevant if you’re very deficient in iodine – probably better to continue getting your isothiocyanates for cancer preventative reasons rather than sweating this stuff.
- 01:16:35 - Rhonda mentions tumor suppressor genes, which are activated by hormesis (good stress triggered by things like isothiocyanates).
- 01:19:20 - Joe brings up Dave Asprey’s take on boiling kale to remove oxalic acid.
- 01:20:10 - Spinach that was either raw, boiled, fried, or frizzled and found that raw and boiling doesn’t affect absorption, but it did very modestly affect minerals in kidneys if raw… didn’t seem to cause kidneys stones (in mice). Probably requires absurd amounts of spinach to cause kidney stones. Just not convinced that it’s bad to eat spinach or kale raw.
- 01:20:20 - Vegetables do make compounds that are sort of “bad for you” but have a net positive effect because they induce hormesis.
- 01:24:33 - JRE consensus of #502 –eating raw spinach and kale is good for you.
- 01:25:10 - Joe throws a curveball by bringing up a documented case of presumed oxalate induced nephropathy (kidney disease) from 1985 to 2010 – only 36 patients documented by paper. Only three patients really suspected that it was caused by raw juicing.
- 01:27:30 - Discussion of vegetable smoothies begins here – specifically using these powerful blenders which leave the fiber in, not juicing.
- 01:28:45 - Brock Lesnar allegedly ate nothing but meat, got diverticulitis.
- 01:29:07 - Putrefying bacteria make nasty smelling hydrogen sulfide farts, use sulfate as source of energy. Needs heme from red meat as a cofactor for creating hydrogen sulfide. Hydrogen sulfide prevents human gut cells from making energy (ATP), and thus causes break-down of gut-mucus barrier.
- 01:32:25 - Brings up episode with Dr. Offitt on Bryan Callen’s podcast. Offitt claims vitamins and antioxidants cause cancer.
- 01:35:20 - Beginning of general debunking of Offitt’s claims.
- 01:36:05 - Randomized double-blind placebo controlled trials are awesome, but using them for nutrition research and expecting the design to perform as effectively is misguided.
- 01:37:30 - Everyone has different levels of vitamins & minerals in their body, but baseline for drugs is always the same: zero. This is an important fundamental difference.
- 01:42:20 - Years of research has to be published even if results aren’t great, and this requires salesmanship. This affects some of the misleading presentation of research.
- 01:43:04 - Joe brings up highly publicized and contentious “Enough is Enough” editorial which was covered at length in podcast #459.
- 01:46:28 - Begin discussion of Vitamin E prostate cancer study (the SELECT trial).
- 01:47:35 - Comparison of Alpha Tocopherol & Gamma Tocopherol forms of vitamin E. Alpha tocopherol serves predominantly as an antioxidant, gamma tocopherol serves as an anti-inflammatory agent by reducing reactive nitrogen species (also an anti-oxidant activity). Alpha tocopherol doesn’t serve the same anti-inflammatory behavior, and this is important because inflammation is a cancer initiator (among other things), and excessive alpha tocopherol consumption depletes gamma tocopherol from tissues.
- 01:50:45 - Study on prostate cancer found that alpha tocopherol and selenium didn’t affect cancer incidence at 5-year followup but at 7.5 year follow-up cancer risk for prostate cancer shot up from taking 400 IU of alpha tocopherol (vitamin E) per day. Importantly, what was found at the 5-year followup was that (relative to baseline) gamma tocopherol was depleted from the tissues. Those who weren’t deficient selenium (& were supplementing) that took the 400 IU of alpha tocopherol didn’t experience the increase in prostate cancer incidence.
- 01:52:05 - One of the proteins selenium is for is important for preventing damage from reactive nitration products. Nitration damage can cause cancer. This is an interesting novel mechanism by which a depletion of gamma tocopherol through a combination of inflammation and an increase in reactive nitratition products might be responsible for the increase cancer incidence found in this study.
- 01:54:00 - Discussion of vegetable smoothie as a good source of vitamin E, and also natural magnesium (from chlorophyll molecules – this was mentioned in JRE #459)
- 01:54:45 - Mixed tocopherol Vitamin E supplements exist which aren’t quite as high dose as 10x the RDA (400 IU) like used in those studies.
- 02:01:18 - RDA for Vitamin D is 600 IU a day. One study showed that 4,000 IU was more appropriate for actually adequately fixing without toxicity in deficient populations. 2000 to 4000 IU of vitamin D is probably a good range except for in cases of severe deficiency.
- 02:03:18 - Offit lumped omega-3 in with “antioxidants that cause cancer”, but this is misleading given the fact that randomized controlled trials have shown that omega-3 supplementation actually reduces all-cause mortality.
- 02:03:39 - 1500 IU of vitamin D a day has been correlated to a 17% reduced cancer risk (overall).
- 02:04:15 - Study based off of self-reported questionaire found that women who took vitamins (supplements) - on a daily basis had the longest telomeres.
- 02:05:45 - She tries to get all her micronutrients, as much as she can, from her diet including vegetable smoothies, fish, etc. However, in addition to her diet she takes: omega-3 fatty acids, vitamin D, a multi-vitamin which has selenium and other trace elements, iodine, B-complex.
- 02:06:30 - B vitamin deficiency is less common due to fortification. However, she supplements B vitamins anyway because changes in mitochondrial membrane rigidity that occurs with age alters the binding affinity (as represented by the constant kM) of important proteins needed to generate energy in the form of ATP which are embedded in the mitochondrial membrane. The Ames lab has partly demonstrated, however, that increasing the concentration of B vitamins compensates for these age related changes caused by changes in the confirmation (shape) of the proteins.
- 02:08:00 - Rhonda increasingly prefers Swanson brand vitamins, but gets omega-3 from nordic naturals.
- 02:10:00 - B vitamins are probably less dangerous because they’re water soluble (excess is more readily excreted, similar to Vitamin C)
- 02:11:00 - Plant form of omega-3, ALA, converts to EPA (normally found in fish) fairly inefficiently at a rate of about 5%.
- 02:12:13 - Microalgae oil is a good alternative to flaxseed oil if you’re trying to meet EPA/DHA needs and avoiding fish oil for one reason or another.
- 02:13:30 - Omega-3 EPA is a potent anti-inflammatory, and DHA is a really component of your cell membranes – and makes up about 40% of the brain.
- 02:13:54 - She takes about 6 pills of her omega-3, which amounts to ~3 “servings” of 800mg of EPA, and 600mg of DHA. (2400 and 1800 mg respectively)
- 02:15:28 - Omega-3 EPA, which can be bought more concentrated for its particular effects, interacts with the arachnidonic acid pathway to reduce inflammation. The arachnicdonic acid pathway is responsible for creating prostaglandins which activate the COX pathway.
- 02:16:05 - 2 grams of EPA per day has been shown to reduce C-reactive protein (CRP), which is a generalized systemic marker for inflammation but is most well known for its use to asses risk of cardiovascular disease.
- 02:17:45 - Omega-3 fatty acids are prone to oxidation. Refrigeration helps with this, however. Also check if they go rancid by smell, if smell bad then probably rancid.
- 02:20:00 - Talks about krill oil. Joe lists off a bunch of points from a Mercola article, and Rhonda points out it’s talking about ordinary effects of omega-3 and suggesting they may not be unique to krill oil.
- 02:27:29 - Recommends Linus Pauling Institute for good, objective source of supplemental micronutrient reviews.
- 02:28:35 - Brief mention of WellnessFX as a useful tool for getting a broad spectrum blood test checking for relevant markers for vitamins, minerals, inflammation, etc.
- 02:31:00 - Whackiness of homepathy discussed. Homeopathy makes use of official sounding measuring system that measures an absurd amount of dilution that actually guarantees that what you’re taking doesn’t actually include the active ingredient the supplement is being marketed for.
- 02:33:25 - Discusses how emerging research showing wisdom teeth has dental pulp stem cells in them and they offer promise for eventually being used as a source of cells that can be differentiated into things like brain cells. You can bank children’s teeth or adult wisdom teeth. Usually like $625 to “process” a tooth, and around $125/year to store it.
- 02:36:16 - They can now take fibroblast cells from skin, the sort that you slough off everyday, and add transcription factors to turn them into “pluripotent” stem cells which can turn into brain cells or liver cells.
- 02:37:35 - Joe brings up study where they took blood of young mice, injected it into old mice, and found the older mice experienced tissue regeneration. Inverse was also true: injecting young mice with old mouse blood increased rate of aging.
- 02:38:54 - Human “methylome” now being studied which is revealing a specific pattern of methylation in DNA that can be used to actually identify the chronological age of people. Since epigenetics is obviously playing an important role in age, this is another promising area of new inquiry that may eventually reveal how to reprogram our cells to “be younger”. Cancer cells show a methylation pattern that is ordinarily associated with old age and are clustered around areas related to DNA repair, mitochondrial metabolism, antioxidant genes (all areas associated with aging).
- 02:43:12 - Scientists are now able to take renal cells excreted in urine and turn them into pluripotent stem cells
- 02:43:45 - Rant about lack of funding in science reducing room for creativity/moonshots.
- 02:48:40 - Joe brings up new studies showing its possible to create artificial blood for transplant.
- 02:50:06 - Inactivating insulin growth factor in c. elegans worms doubles their lifespan from about 15 to 30 days.
- 02:52:40 - Joe asserts (reasonably so) that by age 200 he will most likely be a wizard.
- 02:55:42 - Joe relates the fact that he’s actually been evacuated twice due to large fires in his neck of the woods of L.A.
- 02:57:45 - Rhonda begins plug of iPhone app, website, Twitter, and podcast.