Otto Warburg originally proposed that cancer arose from a two-step process. The first step involved a chronic insufficiency of mitochondrial oxidative phosphorylation (OxPhos), while the second step involved a protracted compensatory energy synthesis through lactic acid fermentation. His extensive findings showed that oxygen consumption was lower while lactate production was higher in cancerous tissues than in non-cancerous tissues. Warburg considered both oxygen consumption and extracellular lactate as accurate markers for ATP production through OxPhos and glycolysis, respectively. Warburg’s hypothesis was challenged from findings showing that oxygen consumption remained high in some cancer cells despite the elevated production of lactate suggesting that OxPhos was largely unimpaired. New information indicates that neither oxygen consumption nor lactate production are accurate surrogates for quantification of ATP production in cancer cells. Warburg also did not know that a significant

Introduction: For half a century, a high level of total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C) has been considered to be the major cause of atherosclerosis and cardiovascular disease (CVD), and statin treatment has been widely promoted for cardiovascular prevention. However, there is an increasing understanding that the mechanisms are more complicated and that statin treatment, in particular when used as primary prevention, is of doubtful benefit.

Areas covered: The authors of three large reviews recently published by statin advocates have attempted to validate the current dogma. This article delineates the serious errors in these three reviews as well as other obvious falsifications of the cholesterol hypothesis.

Expert commentary: Our search for falsifications of the cholesterol hypothesis confirms that it is unable to satisfy any of the Bradford Hill criteria for causality and that the conclusions of the authors of the three reviews are based on misleading

Aging-related muscle atrophy and weakness contribute to loss of mobility, falls, and disability. Mitochondrial dysfunction is widely considered a key contributing mechanism to muscle aging. However, mounting evidence positions physical activity as a confounding factor, making unclear whether muscle mitochondria accumulate bona fide defects with aging. To disentangle aging from physical activity-related mitochondrial adaptations, we functionally profiled skeletal muscle mitochondria in 51 inactive and 88 active men aged 20–93. Physical activity status confers partial protection against age-related decline in physical performance. Mitochondrial respiration remains unaltered in active participants, indicating that aging per se does not alter mitochondrial respiratory capacity. Mitochondrial reactive oxygen species (ROS) production is unaffected by aging and higher in active participants. In contrast, mitochondrial calcium retention capacity decreases with aging regardless of physical act

The graphs tell the whole story, I'm not going to copy over the abstract.

Full paper: https://doi.org/10.1016/S0140-6736(24)02317-1

Despite intensive research, the causes of the obesity epidemic remain incompletely understood and conventional calorie-restricted diets continue to lack long-term efficacy. According to the carbohydrate-insulin model (CIM) of obesity, recent increases in the consumption of processed, high–glycemic-load carbohydrates produce hormonal changes that promote calorie deposition in adipose tissue, exacerbate hunger, and lower energy expenditure. Basic and genetic research provides mechanistic evidence in support of the CIM. In animals, dietary composition has been clearly demonstrated to affect metabolism and body composition, independently of calorie intake, consistent with CIM predictions. Meta-analyses of behavioral trials report greater weight loss with reduced-glycemic load vs low-fat diets, though these studies characteristically suffer from poor long-term compliance. Feeding studies have lacked the rigor and duration to test the CIM, but the longest such studies tend to show metabolic

TLDR Only 7% of Adults have optimal metabolic health! 93% are compromised. This is the single largest health issue the world knows, costing us billions of dollars per day, and millions of lives needlessly cut short.

Background -Few studies have assessed U.S. cardiometabolic health trends—optimal levels of multiple risk factors and absence of clinical cardiovascular disease (CVD)—or its impact on health disparities.

Objectives -The purpose of this study was to investigate U.S. trends in optimal cardiometabolic health from 1999 to 2018.

Methods - We assessed proportions of adults with optimal cardiometabolic health, based on adiposity, blood glucose, blood lipids, blood pressure, and clinical CVD; and optimal, intermediate, and poor levels of each component among 55,081 U.S. adults in the National Health and Nutrition Examination Survey.

Results - In 2017-2018, only 6.8% (95% CI: 5.4%-8.1%) of U.S. adults had optimal cardiometabolic health, declining from 1999-2000 (P trend = 0

Extremely promising results of the application of a strict ketogenic diet to glioblastoma survival rates.

Among the 18 patients participating in the study, 6 adhered to the ketogenic diet for more than 6 months. Of these patients, one patient passed away 43 months after diagnosis, achieving a survival of 3 years; another passed away at 36 months, narrowly missing the 3-year survival mark; and one is still alive at 33 months post-diagnosis but has yet to reach the 3-year milestone and is, therefore, not included in the final survival rate calculation. The remaining 3 are also still alive, completing 84,43 and 44 months of life, respectively. Consequently, the survival rate among these patients is 4 out of 6, or 66.7%. Of the 12 patients who did not adhere to the diet, only one reached 36 months of survival, while the rest have died in an average time of 15.7 ± 6.7 months, with a 3-year survival rate of 8.3%. **Comparing the survival rates of the two groups, we see that the difference

A graduate of the University of Melbourne, Dr Sikaris trained at the Royal Melbourne, Queen Victoria, and Prince Henry's Heidelberg Repatriation Hospitals. He obtained fellowships from the Royal College of Pathologists of Australasia and the Australasian Association of Clinical Biochemists in 1992 and 1997 respectively.

Dr Sikaris was Director of Chemical Pathology at St Vincent's Hospital in Melbourne between 1993 and 1996. A NATA-accredited laboratory assessor, Dr Sikaris specialises in Prostate Specific Antigen, cholesterol and quality assurance and is currently chair of the International Federation of Clinical Chemistry Committee on Analytical Quality. His expertise is highly sought and he has presented extensively at national and international symposiums.

Great resource, that lists known DIAAS scores, and value per 100g of food, even links to the source papers for the values.

Summary (2 minute read): https://faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fasebj.27.1_supplement.127.4

Linked to the title is the full study. Image is figure 2 from the study.

TLDR - Saturated Fat is good for you. Linoleic acid (seed oils, vegetable oils) oils are bad for you.

https://doi.org/10.1136/bmj.i1246 (full paper)

The MCE (1968-73) is a double blind randomized controlled trial designed to test whether replacement of saturated fat with vegetable oil rich in linoleic acid reduces coronary heart disease and death by lowering serum cholesterol. Recovered MCE unpublished documents and raw data were analyzed according to hypotheses prespecified by original investigators. Further, a systematic review and meta-analyses of randomized controlled trials that lowered serum cholesterol by providing vegetable oil rich in linoleic acid in place of saturated fat without confounding by concomitant interventions was conducted.

The intervention group had significant reduction in serum cholesterol compared with controls (mean change from baseline −13.8% v −1.0%; P<0.001). Kaplan Meier graphs showed no mortality benefit for the intervention group in the full rand

cross-posted from: https://sh.itjust.works/post/31544365

Reduced glucose metabolism and mitochondrial dysfunction correlate with increased neuronal death and brain damage during cerebral ischemia and neurodegeneration. Ketone bodies (KBs), such as acetoacetate and β-hydroxybutyrate, serve as crucial alternative energy sources during glucose deficiency. Both KBs and the ketogenic diet (KD) demonstrate neuroprotective effects by orchestrating various cellular processes through metabolic and signaling functions.

TLDR: The current advice that LDL is "bad cholesterol", appears to be outdated, and the actual situation is more complex. In people over 60 high LDL appeared to be protective for mortality.

Conclusions: High LDL-C is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (ie, that cholesterol, particularly LDL-C, is inherently atherogenic). Since elderly people with high LDL-C live as long or longer than those with low LDL-C, our analysis provides reason to question the validity of the cholesterol hypothesis. Moreover, our study provides the rationale for a re-evaluation of guidelines recommending pharmacological reduction of LDL-C in the elderly as a component of cardiovascular disease prevention strategies.

Full Paper at https://pubmed.ncbi.nlm.nih.gov/27292972/

Related to, and following up on the LMHR paper from https://hackertalks.com/post/5835924

TLDR - Alternate day fasting leads to hair follicle damage in mice.

• Common intermittent fasting regimens inhibit hair follicle regeneration in mice
• Fasting selectively eliminates activated HFSCs, but not EpiSCs that maintain epidermis
• Activated adrenal gland-dermal adipocyte crosstalk mediates HFSC apoptosis
• Intermittent fasting inhibits human hair growth in a randomized clinical trial

https://www.cell.com/cell/abstract/S0092-8674(24)01311-4

Nick Norwitz did a great writeup https://staycuriousmetabolism.substack.com/p/fasting-will-make-you-bald-and-how

I haven't found the full paper in the usual places. So I'm relying on the writeup

In both mice and humans topical vitamin E proved to provide enough antioxidant protection to prevent the hair loss.

Globally, there is an increasing prevalence of non-communicable diseases. The morbidity and mortality from these conditions confer a greater economic societal burden. Epidemiological research associates insulin resistance in the etiology of these diseases, but there is limited evidence for the mechanism of damage. Emerging research suggests that hyperinsulinemia, a symptom of insulin resistance, may cause these pathological changes, and therefore be an independent contributor to these diseases. This review shows that hyperinsulinemia, or excessive insulin secretion, should be considered independently to insulin resistance, defined as glucose uptake rate, even though the two conditions are intertwined and will co-exist under normal conditions. Hyperinsulinemia directly and indirectly contributes to a vast array of metabolic diseases including all inflammatory conditions, all vascular diseases, gestational and type 2 diabetes, non-alcoholic fatty liver disease, obesity and certain cance

TLDR - Justifying the TG/HDL ratio as a measure of insulin resistance. The importance of this cannot be over stated, since TG and HDL are part of standard lipid panels it means we have a readily available way to determine people's insulin sensitivity right now without needing special tests. (93% of USA people have insulin resistance)

Atherosclerosis is an immunoinflammatory pathological procedure in which lipid plaques are formed in the vessel walls, partially or completely occluding the lumen, and is accountable for atherosclerotic cardiovascular disease (ASCVD). ACSVD consists of three components: coronary artery disease (CAD), peripheral vascular disease (PAD) and cerebrovascular disease (CCVD). A disturbed lipid metabolism and the subsequent dyslipidemia significantly contribute to the formation of plaques, with low-density lipoprotein cholesterol (LDL-C) being the main responsible factor. Nonetheless, even when LDL-C is well regulated, mainly with statin therapy, a residual risk

Indispensable amino acid (IAA) composition and standardized ileal digestibility (SID) of five animal- and 12 plant-based proteins were used to calculate their respective Digestible Indispensable Amino Score (DIAAS) according to the three age categories defined by the Food and Agriculture Organization (FAO). Mean IAA content and mean SID obtained from each protein dataset were subsequently used to simulate optimal nutritional quality of protein mixtures. Datasets revealed considerable variation in DIAAS within the same protein source and among different protein sources. Among the selected protein sources, and based on the 0.5- to 3-year-old reference pattern, pork meat, casein, egg, and potato proteins are classified as excellent quality proteins with an average DIAAS above 100. Whey and soy proteins are classified as high-quality protein with an average DIAAS ≥75. Gelatin, rapeseed, lupin, canola, corn, hemp, fava bean, oat, pea, and rice proteins are classified in the no quality clai

The focus of this discussion is the impact on ketones, even in the presence of a high carbohydrate diet. i.e. as a drug people consume.

It is a really interesting area of research. A metabolite can function like a epigenetic drug

https://youtu.be/QJEdToMDWZw

25% of these trails are just using supplementation, not dietary interventions.

A Great talk on science literacy, and how even well intended professionals can get mislead by incomplete research. I highly encourage you to watch this video if your curious about reading science literature, and especially in "interpreting' media summaries of flawed papers.

Consider cherry picking by agenda motivated papers

Notice how the One Blue RCT that supported one position was cited exclusively by many more papers then the THREE other RCTs that contra indicated that position?

https://doi.org/10.1136/openhrt-2021-001680

Hiding unhealthy heart outcomes in a low-fat diet trial: the Women's Health Initiative Randomized Controlled Dietary Modification Trial finds that postmenopausal women with established coronary heart disease were at increased risk of an adverse outcome if they consumed a low-fat 'heart-healthy' diet

The Women's Health Initiative Randomized Controlled Dietary Modification Trial (WHIRCDMT) was designed to test whether the US Department of Agriculture's 1977 Dietary Guidelines for Americans protects against coronary heart disease (CHD) and other chronic diseases. The only significant finding in the original 2006 WHIRCDMT publication was that postmenopausal women with CHD randomised to a low-fat 'heart-healthy' diet in 1993 were at 26% greater risk of developing additional CHD events compared with women with CHD eating the control diet. A 2017 WHIRCDMT publication includes data for an additional 5 years of follow-up. It finds that CHD risk i