Notes from the 2023 Linus Pauling Meeting, Sept 19-20, 2023
Food data central now has data on food ingredients, 8,000 foods, 490,000 branded foods
VITAL study of omega-3 supplementation – 77% less CVD in blacks with 1.5 fish per week; no effect in total population
weight loss- short and long term loss; 42% obese in the US
DIETFITS study – compare 6 and 12 months weight loss, low sugar vs low fat
Low carb lost more than low fat, but both groups regained lost weight
Vit C, K, E help low carb weight loss; much more weight loss when restricting saturated fats but not mono-unsaturated fats
1/3rd continued to lose weight in 2nd 6 months-
Microbiome matters; eat a diverse diet to get microbiome diversity
AI is using a computer to do what a human brain would do. AI guidance on infant feeding led to obesity in infants in many cases, so you must use personalized health. Overarching guidances useful but limited!!!
Ketogenic diets, Peter Turnbaugh – how microbiome can increase health
High fat low carb ketogenic diet – eat salmon, nuts, avocadoes,
ketogenic diet and fasting are protective against Multiple sclerosis
BHB (beta-hydroxybutyrate) is key result of ketogenic diet made from fatty acids
Ketogenic diet induces intestinal cells to make BHB, which stimulates Lactobacillus to produce interleukin A, that blocks the immune response which causes MS
BHB may be a useful supplement, they are studying it especially for older people
Nurturing the holobiont in the first 1,000 days
3 STAGES: Pregnancy (270 days) Lactation (365 days) Toddler (365 days)
Most studies are prenatal days. Epigenetics is mostly next 2 stages.
Most specific personalized nutrition is breast milk
Stage 1 is Seeding, stage 2 is feeding, stage 3 is weeding (from taking antibiotics, which should be avoided as they destroy the microbiome)
You and the many other species in and on your body are called the holobiont.
STRONG KIDS 2 COHORT – NIH study from 1 week to years old, with biometric data; 468 kids
Microbiome very different from mom at birth, very similar at age 4
Phases: first year, second year, third year; first solid food at 5.5 months
Exclusively Breast fed are very different from children getting any formula at all, best to give exclusively breast milk.
1,200 genes are differentially expressed between breast vs formula fed infants
This has a huge impact on stem cells and differentiation; There are major differences in gene expression in breast vs formula milk-fed children. There is Tremendous variation in the composition of human breast milk depending on time during feeding, diet of mother, age of infant, etc. Also different from other mammalian breast milks. That is why they are unable to make a baby formula that is not harmful to the health of a baby. Vitamin D and iron after 6 months are recommended for infants who are breast fed.
Defining exposure determinants of dysbiosis, 90% of $4T annual health expense is due to chronic disease; immune disorders are skyrocketing – crohnn,s MS, diabetes, asthma, 3-4 times higher from 1950 to now. Microbiome has a major role in this. Microbiome contents are mediators in how we experience our environment. Maladaptive forms are called dysbosis. Antibiotic household cleaners have a harmful effect on your microbiome.
Different diets have a major effect on the microbiome. A Western diet has a limited variety of microbes, a varied vegetarian diet has a much larger variety of creatures. The greater the diversity, the more protected you are from the environmental hazards in life. Gender and diet have huge effect on infection rate and effects.
Neurotoxicity – early life neurotoxicants may cause effect via microbiome. Benzo-a-pyrene exposure in human kids causes autism, etc.Toxicant affects the microbiome which affects the brain and behavior.
Need vitamin D to slow the production of amyloid plaque in Alzheimers.
50% of colon cancer can be prevented by fiber, grains, exercise, weight control, and limiting meat intake; A study added 10% spinach to diet had a large decrease in colon cancer via the microbiome; spinach increases diversity in microbiome;
Produces linoleate and butanoate that affect gene expression
Liver disease, nonalcoholic fatty liver disease, is in 32% of people worldwide; early diagnosis can prevent this. quercetin increases lipolysis, apoptosis, anti-inflammatory, decreases fatty acid synthesis and thus prevents this common disease. 500mg/d quercetin for 12 weeks reduced cholesterol and alpha TNF, half life of quercetin is 11 hours. Mito-C, my supplement, has quercetin and is designed to be taken twice a day.
Xanthohumol (an ingredient of beer) is a gut health-supplement for inflammatory bowel disease; clinical trial, 8 weeks xanthohumol (XHM) intervention for 8 week study; tested microbiome; XHM changes enterotype (microbiome composition)
Polyphenol-rich food helps neurohealth; anti-inflammatory; prevents Parkinson’s
Milk proteins, some digest, others not; about 1,000 proteins found in milk.
Most proteins are degraded, a few survive like immunoglobulins
IV vitamin C in cancer, 10,000 are being treated this way in the US now, no side effects; No understanding how this works! It extends lifespan, 100g vc IV, high dose activates TCA cycle rather than glycolysis in normal cancer for energy; carnitine goes up due to VC, so acyl-carnitine gets energy to mitochondria, that triggers apoptosis, so this is selectively toxic to cancer cells.
Seaweeds in anti-obesity – $20 billion market for seaweed-Nori and Dulse types of seaweed; dulse tastes like bacon; dulse reduced obesity, blood glucose, reduced liver weight and fatty liver, and leptin levels – Nori did not have these effects; DULSE is extraordinary, want to buy it.
Smokers, diabetics, obese, require more vitamin C
Centella asiatica for cognition and anxiety relief; it is Gotu Kola, ayurvedic rejuventating herb, Tested mice behavior with Gotu Kola. Improved memory from old to better than young; also for cognitive function; anxiety; may be due to triterpene samponins and aglycones, etc.
Fiber helps microbiome
Sulfurophanes (SFN) are depleted in 72 hrs. Mixed SFN from broccoli greatly aided survival from Alzheimer’s
Metabolic rate for burning excess calories much higher in vitamin/mineral nourished people.
Vitamin K deficiency increases substantially with age. Bone strength 100% with vitamin K supplementation, 97% without.
DAY 2
Healthspan – high functioning period of life, don’t have way to measure this yet, no definition
useful therapies-rapamycin, caloric restriction, parabiosis, senolytics
UTUBE video: Aging: separating the science from the snake oil
Clocks: epigenetic age, telomere age, inflammation age
Healthspan of humans is currently decreasing , sick span is increasing dramatically
Aging is reduced resilience, altered homeostasis; cognitive decline-frailty
Force generation declines faster than muscle mass
We are in the silver tsunami. Threshold effect in disease appears before damage is visible
Calcium supplements disrupt aging and cause harm
Immunology, inflammation – 1,000 person study; can predict frailty 7 years prior to occurence; immunosenesence is drop in T-cells; arterial stiffening
iAGE is marker they have developed, blood sample shows immune proteins etc that allows calculation of how old you are in healthspan.
They have developed an anitinflammatory drug gene map, which they can use to select foods with similar effects to drugs, so you will not need those drugs.
So what to eat – salmon, herring, pumpkin, cruciferious veggies
Expt to increase microbiome diversity – reduces cognitive deterioration
Drug discovery is slow and expensive; 90% from mouse to human fails; $2 B/drug
Astronauts suffer features of aging from zero gravity; NASA has zero gravity simulator, do this with cells and find tons of effects all related to aging
Developing drugs to treat this. Quercetin reverses 70% of aging effects
Heart, brain, muscle organoids have age effects under microgravity
Immune genes and age genes overlap 50%
Amount of protein useful in the diet depends on individual, we do not have useful dietary guidelines. One should inhibit the mTOR pathway to increase healthspan, but high protein diet induces mTOR, so reduce protein intake. But high protein reduces sarcopenia; obese + high protein diet promotes cancer.
Chronic inflammation promotes autoimmunity; rapamycin is anti-inflammatory, a 10 week course can reduce chronic inflammation!
What to do About Getting Older: Healthy Aging Interventions
Cellular senescense; first step is replicative stress- cells don’t divide, but don’t die.
Many become cancerous; no marker for senescent cells; large increase in mTOR, misfolded proteins-misfolded proteins cause senescent; Downs syndrome is from senescent cells; they accumulate in fat in obesity; cause frailty; threshold phenomenon for number of senescent cells; they secrete something harmful that circulates in the body without the cells moving; caloric restriction decreases senescent cells; we need agents to kill senescent cells – anti-apoptotic factors harm other cells but not senescent cells. Caloric restriction seems wise for this. Quercetin is also useful for this!
30 trials now testing senolytics; gait speed is vital to healthspan
So senolytics work in destroying senescent cells, extend life and health.
Doctors won’t transplant older people’s organs because they have senescent cells.
Loss of proteostasis; proteosome degrades old proteins that are targeted by ubiquinylation.
Proteosome damage causes brain diseases. Can activate proteosomes by natural compounds – Quercetin makes old fibroblasts young again! Anti-oxidants activate proteosomes
COSMOS-Mind Study – cocoa supplement and multivitamins outcomes study of the mind
Insulin use is hazardous for cognition. Cocoa extract is extremely beneficial esp for heart, but no effect on brain function. A Daily MVM helped everyone, even those on great diet
Slows cognitive aging by 60%; but no effect on mild cognitive impairment. In particular, most people need more vitamin D and K, thiamine, selenium (which can be gotten by eating a Brazil nut daily) are key deficiencies
Inflammation is caused by IL1 IL6 TNF-alpha. (IL is interleukin)
Immunosenesence is inflammaging– as iflammaging increases, specific immunity decreases, resolution decrease, memory cells decrease
Inflamaging occurs with aging because the microbiome changes from eating less diverse fruits and veggies.
Why – Diet changes; all medications affect microbiome, decreased physical activity, need activity to push microbiome into body
Also more cancer from lower specific immunity
Also ILs cause behavioral effects IL1-tired and depressed; IL6 anxiety fatigue, pain; TNF hostility and pain, bidirectional – ILs cause behavior causes ILs
Worry causes IL6 increase, so don’t worry, be happy for your health.
Resolution – TGFbeta is natural anti-depressant – It is made in the body from vitamins D and A! probiotics Bifidobacterium; short chain fatty acids; microbial metabolites convert whole grains to post-biotics – esp short chain fatty acids (SCFA) and over 1,000 others found in stool. Different foods provide different post-metabolites; e.g. neurotransmitters
SCFA stimulates regulatory T cells that decrease inflammation, increase resolution (recovery of immune system).
Fecal transplant – old to young mice – young to old reduces inflammation; improves macular degeneration;
Post-biotics – chemicals produced in the microbiome resulting from digestion of pre-biotics
Heat killed bacteria from the microbiome are called para-biotics – chemicals plus dead cells
Thaena corp gets poop from 5 exceptionally healthy people
Increase microbiome diversity by plant-based, pre and post biotics, fermented foods
Do we need more fiber? Need yeast, milk, lots of other stuff beyond plant fiber
What to remove from diet? It is unclear.
Ketogenic diet for parkinsons-30% get way better, 30% same, 30% worse; meat good for some, not others
pH is most important, so eating grapes helps balance pH of diet.
prebiotics – spices are all great, leeks, onion, mushrooms, yeast, astaxanthin
Zinc from nuts and legumes, whole grains, seafood, 40mg UL, 10-15 mg daily is best.
It is bound to protein – #1 is oysters, double RDA from one oyster; no good test for how much you have in you, it is a great antioxidant
Zn is for p53, main DNA repair enzyme; zinc alters microbiome toward adequacy
Older adults more likely to be zn deficient, absorb it poorly
24 Zn transporter enzymes, but they do not change with age, except zip6, gene hypermethylated, zn supplementation increases CD4T cells, reduces inflammation
ZIP8 is one of top 10 variants in genome and disease. Zip imports Zn into the cells.
Northern European 10-20% risk of this defect. Zip8 is the main response to immune function response.
The gut lung axis – zn alters microbiome;
In SCFAs, butyric acid is 95% of microbiome output, and is an immunomodulatory molecule.
Butyric acid educates monocytes to be macrophages effectively, need it right from the start.
Butyric acid needs to be present to program macrophages for pneumonia
Zinc slows duration of a cold, helps with resolution for recovery quicker
Now Alzheimers disease is defined by amyloid beta peptide. Tau aggregation occurs later.
PET imaging diagnosis, low amyloid in Central spinal fluid because trapped in the brain
1/3rd over 65 developing dementia with amyloid pathology. 15 million (20%) over 65 have MCI. 50-80% with MCI get dementia in 5 years, early diagnosis can delay or prevent dementia
Diet has great role to play for AD-Mediterranean diet protective; western increases risk
Brain energy switches from glucose to fat for energy during Alzheimers
Keto diet is best treatment for epilepsy!
Keto macro diet tested: Healthy fats 65-75% protein 15-30%; carbs 5-10%
Caused ketosis; cholesterol dropped a lot; triglycerides way down
Increased amyloid in CSF which is good.
Enhanced blood flow to the brain regions; so ketones being used much better with ketosis diet
Ketogenic diet reversed Alzheimer lipid problems; changed microbiome
Mitochondria much healthier;
people with dementia should eat a very high fat very low carb diet
phytochemicals to prevent neurodegeneration
26,000 molecules in the diet; vitamin P-by Albert Szent-Gyorgyi – is flavanone; flavonoids can delay neurodegeneration.
Molecules neuroprotective in both drosphila and nematode
Vitamin K and the aging brain. K1, K2, K3
In diet – kale, olive oil, broccoli, cheese – have 4-800 mcg
No RDA yet; 120 mcg/day is intake; older men 65% deficient; 45% of women
Need veggie diet to get enough; 16 vit K dependent proteins; needed for blood coagulation; many proteins in the brain and regulates calcium – osteocalcin; 11 forms of vitamin K; all convert to menoquinone 4, not produced by bacteria; it is a ligand related to brain aging but
No one knows role in brain;
Green leafy vegetables main food for brain cognitive function retention with age.
Those with greens do best, esp phylloquinone – vit K
All menoquinone4 (MK4) in the brain, but not stable
Less MK4, lower brain function
Low vitamin K fatal for males
Neurogenesis relies on vitamin K in hippocampus
Nato is food common in Japan; that has menaquinone and spermidine
People on warfarin should not eat leafy green vegetables; get off warfarin by taking fish oil
