TLDR - Women who had a high omega-6 to omega-3 ratio in their fat where at elevated risk for developing breast cancer.

Seed oils (vegetable oils) are the major dietary driving source of omega-6s. It seems reasonable that seed oils have a outsized cancer risk.

>The ratio of omega-3 to omega-6 fatty acids, especially the long-chain eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) to arachidonic acid (AA) ratio, is inversely associated with breast cancer risk. We measured the association between cytologic atypia, a biomarker for short-term risk of breast cancer development, and omega-3 and omega-6 fatty acid intake and levels in blood and breast tissue. Blood and benign breast tissue, sampled by random periareolar fine-needle aspiration (RPFNA), was obtained from 70 women at elevated risk for breast cancer. Self-reported dietary intake was assessed by the NCI's Food Frequency Questionnaire. The fatty acid composition of five lipid compartments, red blood cell, plasma and breast phospholipids, and plasma and breast triaclyglycerides (TAG), was analyzed by gas chromatography as weight percent. Median daily intakes of EPA+DHA and total omega-3 fatty acids were 80 mg and 1.1 g, respectively. The median total omega-3:6 intake ratio was 1:10. Compared with women without atypia, those with cytologic atypia had lower total omega-3 fatty acids in red blood cell and plasma phospholipids and lower omega-3:6 ratios in plasma TAGs and breast TAGs (P < 0.05). The EPA+DHA:AA ratio in plasma TAGs was also lower among women with atypia. This is the first report of associations between tissue levels of omega-3 and omega-6 fatty acids and a reversible tissue biomarker of breast cancer risk. RPFNA cytomorphology could serve as a surrogate endpoint for breast cancer prevention trials of omega-3 fatty acid supplementation.

Full paper at above link

>Conclusions: A meta-analysis of prospective epidemiologic studies showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD. More data are needed to elucidate whether CVD risks are likely to be influenced by the specific nutrients used to replace saturated fat.

General Paper Analysis - This is a meta-analysis of epidemiology. While the meta aspect gives great confidence in the results, we have to be mindful that epidemiology is the weakest of scientific data. A pyramid built on sand - as it were.

But as the paper itself says >such studies have caveats, including a reliance on nutritional assessment methods whose validity and reliability may vary (25), the assumption that diets remain similar over the long term (26) and variable adjustment for covariates by different investigators. Nonetheless, a summary evaluation of the epidemiologic evidence to date provides important information as to the basis for relating dietary saturated fat to CVD risk.

Full paper at the link.

TLDR - Fat is good for you, sugar/carbs not so much

Full paper can be found here

>Higher carbohydrate intake was associated with an increased risk of total mortality

>Intake of total fat and each type of fat was associated with lower risk of total mortality

>Higher saturated fat intake was associated with lower risk of stroke

>Total fat and saturated and unsaturated fats were not significantly associated with risk of myocardial infarction or cardiovascular disease mortality.

>Global dietary guidelines should be reconsidered in light of these findings.

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TLDR - as insulin resistance goes up, diseases increase.

2001!!!!! Full paper here

>The current study was initiated to evaluate the ability of insulin resistance to predict a variety of age-related diseases. Baseline measurements of insulin resistance and related variables were made between 1988-1995 in 208 apparently healthy, nonobese (body mass index < 30 kg/m2) individuals, who were then evaluated 4-11 yr later (mean +/- SEM = 6.3 +/- 0.2 yr) for the appearance of the following age-related diseases: hypertension, coronary heart disease, stroke, cancer, and type 2 diabetes. The effect of insulin resistance on the development of clinical events was evaluated by dividing the study group into tertiles of insulin resistance at baseline and comparing the events in these 3 groups. Clinical endpoints (n = 40) were identified in 37 individuals (18%) of those evaluated, including 12 with hypertension, 3 with hypertension + type 2 diabetes, 9 with cancer, 7 with coronary heart disease, 4 with stroke, and 2 with type 2 diabetes. Twenty-eight out of the total 40 clinical events were seen in 25 individuals (36%) in the most insulin-resistant tertile, with the other 12 occurring in the group with an intermediate degree of insulin resistance. Furthermore, insulin resistance was an independent predictor of all clinical events, using both multiple logistic regression and Cox's proportional hazards analysis. The fact that an age-related clinical event developed in approximately 1 out of 3 healthy individuals in the upper tertile of insulin resistance at baseline, followed for an average of 6 yr, whereas no clinical events were observed in the most insulin-sensitive tertile, should serve as a strong stimulus to further efforts to define the role of insulin resistance in the genesis of age-related diseases.

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This graph is all you need to know, as insulin resistance goes up, more diseases increase.

• CVA - Cerebrovascular accident
• Type 2 - Diabetes Type 2
• CHD - Coronary Heart Disease
• CA - Cancer
• HT - Hyper Tension

Ben Bikman does a deep dive into hormonal roots of male infertility! This is part of his excellent "Metabolic Classroom series"

TLDR - Stay active and exercise into old age. Sarcopenia is not inevitable.

> DOI: 10.3810/psm.2011.09.1933

>Aging is commonly associated with a loss of muscle mass and strength, resulting in falls, functional decline, and the subjective feeling of weakness. Exercise modulates the morbidities of muscle aging. Most studies, however, have examined muscle-loss changes in sedentary aging adults. This leaves the question of whether the changes that are commonly associated with muscle aging refl ect the true physiology of muscle aging or whether they reflect disuse atrophy. This study evaluated whether high levels of chronic exercise prevents the loss of lean muscle mass and strength experienced in sedentary aging adults. A cross-section of 40 high-level recreational athletes (“masters athletes”) who were aged 40 to 81 years and trained 4 to 5 times per week underwent tests of health/activity, body composition, quadriceps peak torque (PT), and magnetic resonance imaging of bilateral quadriceps. Mid-thigh muscle area, quadriceps area (QA), subcutaneous adipose tissue, and intramuscular adipose tissue were quantified in magnetic resonance imaging using medical image processing, analysis, and visualization soft- ware. One-way analysis of variance was used to examine age group differences. Relationships were evaluated using Spearman correlations. Mid-thigh muscle area (P = 0.31) and lean mass (P = 0.15) did not increase with age and were significantly related to retention of mid-thigh muscle area (P  0.0001). This occurred despite an increase in total body fat percentage (P = 0.003) with age. Mid-thigh muscle area (P = 0.12), QA (P = 0.17), and quadriceps PT did not decline with age. Specific strength (strength per QA) did not decline significantly with age (P = 0.06). As muscle area increased, PT increased significantly (P = 0.008). There was not a significant relationship between intramuscular adipose tissue (P = 0.71) or lean mass (P = 0.4) and PT. This study contradicts the common observation that muscle mass and strength decline as a function of aging alone. Instead, these declines may signal the effect of chronic disuse rather than muscle aging. Evaluation of masters athletes removes disuse as a confounding variable in the study of lower-extremity function and loss of lean muscle mass. This maintenance of muscle mass and strength may decrease or eliminate the falls, functional decline, and loss of independence that are commonly seen in aging adults.

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>Despite concerted efforts to improve diet quality and reduce malnutrition, micronutrient deficiencies remain widespread globally, especially in low- and middle- income countries and among population groups with increased needs, where diets are often inadequate in iron, zinc, folate, vitamin A, calcium, and vitamin B12. There is a need to understand the density of these micronutrients and their bioavailability across diverse foods and the suitability of these foods to help meet requirements for populations with high burdens of micronutrient malnutrition

Full paper available at the above URL

a 2021 paper on bioavailability of nutrients needed per day from different whole food sources. I.E. It's not just the macronutrients in the food, it's not just the micronutrients in the food, its how much of the nutrients are bioavailable (absorbed) when consumed.

If you eat 100g of protein but only absorb 4g, your still deficient, etc.

"we provide a direct molecular mechanism for the regulation of misfolded proteins by ketone bodies and related metabolites."..."Given that proteostatic mechanisms like autophagy are known to be activated by nutrient deprivation, it is unsurprising that evolutionary pressures would encourage the clearance of patho- genic proteins during ketosis to promote cellular health in organisms seeking additional substrate for ATP production. In this situation, ketone bodies are janitors of damaged proteins, chaperoning away molecular waste so organisms can operate at peak molecular fitness. This mechanism can be leveraged for therapeutic development in aging and NDDs,"

Summary: >Loss of proteostasis is a hallmark of aging and Alzheimer disease (AD). We identify β-hydroxybutyrate (βHB), a ketone body, as a regulator of protein solubility. βHB primarily provides ATP substrate during periods of reduced glucose availability, and regulates other cellular processes through protein interactions. We demonstrate βHB-induced protein insolubility is not dependent on covalent protein modification, pH, or solute load, and is observable in mouse brain in vivo after delivery of a ketone ester. This mechanism is selective for pathological proteins such as amyloid-β, and exogenous βHB ameliorates pathology in nematode models of amyloid-β aggregation toxicity. We generate libraries of the βHB-induced protein insolublome using mass spectrometry proteomics, and identify common protein domains and upstream regulators. We show enrichment of neurodegeneration-related proteins among βHB targets and the clearance of these targets from mouse brain. These data indicate a metabolically regulated mechanism of proteostasis relevant to aging and AD.

Full paper available at Cell.com

https://youtu.be/jpNU72dny2s

>Robert H. Lustig, M.D., M.S.L. is Professor emeritus of Pediatrics, Division of Endocrinology at the University of California, San Francisco (UCSF). He specialises in the field of neuroendocrinology, with an emphasis on the regulation of energy balance by the central nervous system. His research and clinical practice has focused on childhood obesity and diabetes. Dr. Lustig holds a Bachelor’s in Science from MIT, a Doctorate in Medicine from Cornell University. Medical College, and a Master’s of Studies in Law from U.C. Hastings College of the Law.

>Dr. Lustig has fostered a global discussion of metabolic health and nutrition, exposing some of the leading myths that underlie the current pandemic of diet-related disease. He believes the food business, by pushing processed food loaded with sugar, has hacked our bodies and minds to pursue pleasure instead of happiness; fostering today’s epidemics of addiction and depression. Yet by focusing on real food, we can beat the odds against sugar, processed food, obesity, and disease.

>Fructose consumption has increased considerably over the past five decades, largely due to the widespread use of high-fructose corn syrup as a sweetener1. It has been proposed that fructose promotes the growth of some tumours directly by serving as a fuel2,3. Here we show that fructose supplementation enhances tumour growth in animal models of melanoma, breast cancer and cervical cancer without causing weight gain or insulin resistance. The cancer cells themselves were unable to use fructose readily as a nutrient because they did not express ketohexokinase-C (KHK-C). Primary hepatocytes did express KHK-C, resulting in fructolysis and the excretion of a variety of lipid species, including lysophosphatidylcholines (LPCs). In co-culture experiments, hepatocyte-derived LPCs were consumed by cancer cells and used to generate phosphatidylcholines, the major phospholipid of cell membranes. In vivo, supplementation with high-fructose corn syrup increased several LPC species by more than sevenfold in the serum. Administration of LPCs to mice was sufficient to increase tumour growth. Pharmacological inhibition of ketohexokinase had no direct effect on cancer cells, but it decreased circulating LPC levels and prevented fructose-mediated tumour growth in vivo. These findings reveal that fructose supplementation increases circulating nutrients such as LPCs, which can enhance tumour growth through a cell non-autonomous mechanism.

TLDR - "In all cases, diets supplemented with HFCS resulted in faster tumour growth compared with control diets"

I'm having trouble finding the full text of the paper, normal avenues 🦜 are a little behind

https://pubmed.ncbi.nlm.nih.gov/39633044/

>Comparing biomarker profiles measured at similar ages, but earlier in life, among exceptionally long-lived individuals and their shorter-lived peers can improve our understanding of aging processes. This study aimed to (i) describe and compare biomarker profiles at similar ages between 64 and 99 among individuals eventually becoming centenarians and their shorter-lived peers, (ii) investigate the association between specific biomarker values and the chance of reaching age 100, and (iii) examine to what extent centenarians have homogenous biomarker profiles earlier in life. Participants in the population-based AMORIS cohort with information on blood-based biomarkers measured during 1985-1996 were followed in Swedish register data for up to 35 years. We examined biomarkers of metabolism, inflammation, liver, renal, anemia, and nutritional status using descriptive statistics, logistic regression, and cluster analysis. In total, 1224 participants (84.6% females) lived to their 100th birthday. Higher levels of total cholesterol and iron and lower levels of glucose, creatinine, uric acid, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, lactate dehydrogenase, and total iron-binding capacity were associated with reaching 100 years. Centenarians overall displayed rather homogenous biomarker profiles. Already from age 65 and onwards, centenarians displayed more favorable biomarker values in commonly available biomarkers than individuals dying before age 100. The differences in biomarker values between centenarians and non-centenarians more than one decade prior death suggest that genetic and/or possibly modifiable lifestyle factors reflected in these biomarker levels may play an important role for exceptional longevity.

Full PDF of paper is available at the above link

>Higher levels of total cholesterol and iron and lower levels of glucose, creatinine, uric acid, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, lactate dehydrogenase, and total iron-binding capacity were associated with reaching 100 years.

Implies Cholesterol is good, and Glucose control is important, which I think means insulin sensitivity is a key factor in living to 100

One really good aspect of this study vs the normal "blue zone" observational studies, is there is hard data, accurate biographic data (i.e. no poor record keeping, or incentives to lie about age).

A very interesting overview of concussion protocols, the multiple windows of concussive damage, the brain physiology both at the time of impact and during recovery.

Dr. Mason covers some papers that overview dietary interventions post concussion to look at recovery rates.

> Dr. Sanjeev Balakrishnan holds a Master of Medicine in Family Medicine from the National University of Singapore and is currently a GP working in Perth, Western Australia. Dr. Balakrishnan has more than two decades of experience and is very passionate about the management of obesity, type 2 diabetes and metabolic syndrome through healthy eating. He is an advocate for the low carbohydrate-high healthy fat diet and is the creator of Low Carb WA. He is a fully credentialed Family Physician in Singapore and is a Fellow of the Royal Australian College of General Practitioners.

A review of different mental health models over time, and the possible impact of nutrition, as well as discussions of areas of exciting possible research.

>Recent headlines talk about Dr. Dean Ornish’s study, which suggests that a whole-food, plant-based diet might help treat Alzheimer’s dementia. This idea sounds hopeful since current treatments have limited efficacy. But how solid is the science behind this claim? In this video, we take a closer look at the Ornish study, checking its methods, results, and limits to see what it really tells us about using a comprehensive lifestyle approach and a plant-based diet for Alzheimer’s.

>Watch to learn more about the evidence (or lack of it) supporting a vegan diet for Alzheimer’s and to find out how to understand scientific studies better.

>Studies Mentioned >Effects of intensive lifestyle changes on the progression of mild cognitive impairment or early dementia due to Alzheimer’s disease: a randomized, controlled clinical trial https://pubmed.ncbi.nlm.nih.gov/33622392/

>Randomized crossover trial of a modified ketogenic diet in Alzheimer's disease https://pmc.ncbi.nlm.nih.gov/articles/PMC11157928/

A really interesting paper analysis video. Basically, we don't have the right research to say Vegan is the best diet for Alzheimers, and feedback is given on how we could structure a study to give us more direct data.

>Dr. Matthew Phillips is a neurologist and Director of Neurology at Waikato Hospital in New Zealand. His emphasis is on applying metabolic strategies in healthcare to heal many difficult disorders at their core through fasting and ketogenic diets. https://www.metabolicneurologist.com/papers

A fascinating discussion about designing research protocols for mitocondrial metabolic research with cancer patients, alzheimer's patients, als, parkinsons, etc. A really illuminating walk behind the curtain.

Are they worth it?

What makes them good?

Did it have lasting impact on your life after you finished?

> Dr. Roshani Sanghani, MD is the founder of Reisaan Health in Mumbai, India. She is a superspecialist in hormone imbalance in patients with Type 2 and Type 1 diabetes and she is American board-certified in Endocrinology, Diabetes, and Metabolism. Discover the truth about diabetes management in this eye-opening discussion with Dr. Eric Westman and Dr. Roshni Sogani. In this video, they reveal powerful insights into reversing diabetes through lifestyle changes, nutrition, and low-carb diets, going beyond traditional medical advice. Dr. Sogani, a renowned endocrinologist, shares her journey of moving away from medication-focused treatment and helping patients take control through comprehensive lifestyle solutions. If you've ever felt frustrated by conventional diabetes treatments or wanted to know how to manage diabetes naturally, this video is a must-watch!

She is doing a book circuit for her new book "Turn around Diabetes: The Step-by-Step Guide to Navigate Type 2 (and Type 1) Diabetes with Less Medication"

What makes this really interesting is she focuses on the approach to vegan diabetes management, most vegan food has a large carb to protein ratio, so its a challenging environment in which she has outlined a path to success.

A nice presentation of a study of 99 participants over 6 months and their diabetes control, using a low carb (20% of diet) intervention.

HbA1c down by 1% in 3 months!

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20% is a low carb diet, not a ketogenic diet, its 85g of carbs, or about 340 kcal from carbs per day.

I'm really impressed at the improvements in this cohort with a mild dietary intervention, promising work!

A interesting THEORY of action regarding lipid rafts in the cell membrane and the observed effects of both elevated blood glucose and seed oils, and possibly statins, in impacting insulin resistance (these seem like different things, but they seem to have similar outcomes). He goes over the theory at the 32 minute mark, before that he sets up background on the lipid system.

phospholipid bilayer is not a homogenous ocean of phospholipids, but is composed of islands of phospholipids (rafts) that float in the cell membrane, the lipid raft composed of large amounts of cholesterol and insulin receptors.

Depletion of lipid raft cholesterol detrimental to lipid raft function and impairing insulin receptor activation - leading to insulin resistance.

Anything that impacts that lipid raft/cholesterol function seems central to insulin resistance, and would link excess sugar intake and oil intake with insulin resistance as they both have demonstrated impact on these rafts.

Low Carb Down Under - Grant Schofiled PhD