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Linus Pauling Institute Meeting Complete Notes May 2013

This meeting, held every two years in Corvallis, OR, is the best nutrition meeting I have ever attended, having gone every time. Below are my complete unedited notes, a feast for Memorial Day. I will send out an edited version later when I have time. Happy Memorial Day. One million Americans have died in wars. I am a member of Veterans for Peace, and in classes wear a button, "Teach peace".

Diet and Optimum Health 2013  The programfeatures individual sessions including:
•           Omega-3 Fatty Acids, Fatty Acid Oxidation and Cardiovascular Health
•           Diet and Epigenetic Impacts on Disease and Aging
•           Vitamin D—Health Benefits Beyond Bone
•           Health Effects and Mechanisms of Action of Xanthomumol
•           Health Benefits of Vitamin C: Beyond Scurvy
•           Micronutrients in Fertility and Pregnancy
•           Whole Food Approaches to Disease Prevention

I. OMEGA-3 FATTY ACIDS AND FATTY ACID OXIDATION IN CARDIOVASCULAR AND BRAIN HEALTH
A. Health benefits of omega-3 fatty acids, Richard Deckelbaum, MD, Columbia University, New York, NY
Hippocrates and Pliny the Elder 1st century recommended fish oil.  50% of the retina is DHA. Fish oils are antioxidants, regulate genes, reduce risk for depression, cancer, heart disease and stroke. 1. Liver fat reduced by omega-3, increased by sat’d fat. 2. Fish oil reduces sudden death and arrhythmias, hypertension, inflammation.  Acute administration of fish oil after heart attacks prevents much damage, reduces infarct size. 3. For brain, omega-3 reduces stroke damage 50-75%, while omega-6 increases damage substantially.
C. Omega-3 fatty acids, cardiac mitochondrial function and heart failure: From lipotoxicity to lipoprotection, William C. Stanley, PhD, University of Sydney, Sydney, Australia
30% of heart volume is mitochondria, heart is 5-10% DHA. 5-6 million have heart disease.  Fish oil decreases heart failure 5-10%. Muscle loses force to eject blood, but DHA strengthens muscle.  MUFA prolongs heart life a lot.  Mediterranean diet with nuts or 1 liter olive oil weekly caused 20% reduction in stroke and CVD.  Olive oil activates omega-3 elongation, turns on fatty acid oxidation genes.
D. Prospective cohort studies and randomized controlled trials on omega-3 fatty acids and cardiovascular diseases, Dariush Mozaffarian, MD, DrPH, Harvard School of Public Health, Boston, MA
At least 7 of top 20 causes of death are dietary. Average DHA/EPA intake is only 100 mg.  Getting 250mg daily decreases sudden death 36%, decreases total mortality 40% in highest vs lowest quartile of fish oil intake.  DHA helps brain development in utero.
E. Omega-3 fatty acids in the modulation of the inflammatory response and neuroprotection, Don Jump.
Carbohydrates cause a large increase in serum fatty acids.  Western diet inflames the liver.  DNA is much better than EPA for increasing omega-3 and decreasing omega-6 levels in serum.
II. VITAMIN D – HEALTH BENEFITS BEYOND BONE

  1. Vitamin D requirements for optimum health, Robert P. Heaney, MD, Creighton University

RDA is 600IU. 10,000IU are safe. No shared definition of normal in nutrition policy. 80nM Vitamin D in serum seems ideal, enables calcium absorption. Osteoporotic fractures are reduced 33% from just 800 IU vs 600 IU. Vitamin D is important for DNA expression.  80nM vitamin D reduced cancer 77% versus 60nM control. Yet 84% of mature women are below an acceptable level, as are 60-98% of children.  600 IU daily gives 20nM serum, 1,500IU gives 30nM, while 5,000IU recommended by Heaney and panel of vitamin D experts gives 80nM.

  1. Vitamin D and the brain, Thomas H. J. Burne, PhD, The University of Queensland, St. Lucia, Queensland, Australia

Vitamin D is important for brain neurons, astrocytes, microglia, etc. Critical for dopamine production, which is deficient in people with schizophrenia.  In winter when pregnant women are likely to be more deficient, more children are born with schizophrenia. 

  1. Vitamin D and cancer prevention, David Feldman, MD, Stanford University School of Medicine, Stanford, CA

Vitamin D is like a hormone.  Obesity and vitamin D deficiency both increase risk of breast cancer.  Aromatase inhibitors are main treatment for breast cancer; Vitamin D induces calcitriol which is a natural aromatase inhibitor.  Vitamin D reduces aromatase, prostaglandin, COX-2, and prostaglandin receptor synthesis, all reducing breast cancer risk.  Obesity doubles tumor size, vitamin D cuts size in half.  He recommends 5,000 IU/kg as treatment for breast cancer.  Breast cancer survivors take 4, 5, even 10,000 IU Vitamin D daily.  Note Upper Limit I 10,000 IU which is considered safe.

  1. Pilz, Vitamin D and Cardiovascular Disease

CV mortality and diabetes are both seasonal in nature, thus likely to depend on vitamin D deficiency. Deficiency is related to hypertension, diabetes, kidney disease, inflammation and obesity, though deficiency does not cause obesity.  If children get vitamin D, risk of type I diabetes decreases by 5x, and pregnant women should get 2,000 IU daily.  For heart health, vitamin D supplementation reduces risk, calcium supplements increase risk. Vitamin D is specific to heart, prevents hypertrophy.  Best level is 75-90 nM in serum.  For every 161 people taking supplements, one fewer will die of sudden death heart disease. Infants should get at least 400-800 IU daily.

III. HEALTH EFFECTS AND MECHANISMS OF ACTION OF XANTHOHUMOL (XH)
A. Xanthohumol inhibits hyaluronan (H) export and prevents osteoarthritis (OA)
Peter Prehm, PhD, Münster University Hospital, Münster, Germany
X inhibits H and prevents OA. Overproduction of H leads to tumors, OA, edema, displaces proper cell surface receptors.  90% of 60 yr olds have OA, no drug yet available
Horny goat weed is cheap substitute for Viagra. X blocks cartilage degradation.  Curcumin also helps prevent cartilage degradation.  It and hylin, also in turmeric, preserve cartilage and slow OA. They also inhibit cancer and other inflammations like OA.

B. Hops, xanthohumol and women's health
Richard van Breemen, PhD , University of Illinois, Chicago, IL
Try brocolini, vegetable like broccoli.  Safe alternatives to hormone replacement therapy include black cohash, X, and angelica. X significantl;y inhibits many liver enzymes, but safe at dietary levels. One hops supplement per day decreases hot flashes.  Black cohash is popular but actually increases hot flashes.

C.  for treatment of metabolic syndrome
Fred Stevens, PhD, Linus Pauling Institute, Oregon State University, Corvallis, OR
He started X research, for metabolic syndrome. 10% of  hops are X.  X has a half0life of 17 hrs.  Reduces plasma glucose and obesity. X increases glutathione 10x and is great antioxidant. Takes 20 liters of beer to equal one hops capsule.

IV. DIET AND EPIGENETIC IMPACTS ON DISEASE AND AGING
A. Diet, epigenetics and fetal origin of adult-onset diseases
Kent Thornburg, PhD, Oregon Health & Science University, Portland, OR
Obesity and diabetes have increased in parallel.  1958 1% of US, 1999 10%; 2050 33%. Birth weight has decreased from 1990 to 2005 from 40 to 80%. But risk of mortality from CVD is inversely related to birth weight.  Odds ratio is 8x higher for 5.5 lb birth vs 9.5 lb.  Also causes hypertension.  Low Birth weight affects CV, metabolic and neurological effects.  During the 7 to 10 days between fertilization and implantation, egg requires enough protein to survive. Grandmother nourishes those eggs that are in the mother after birth. Of lifetime of 30,000 days, first 1,000 (age 0-3) are most important for health. During 1st 3 years, poor nutrition and stress cause high cortisol causing low oxygen levels: structural damage causes 3x more nephrons in kidney and fewer heart cells; epigenetic effects that show up in grandchildren. So both high and low calorie intake causes troubles for child and grandchildren. 7 to 15% of babies have a low number of heart cells.  Much of chronic disease is caused by poor pre-natal nutrition.  Environmental toxins are not as important as stress and poor nutrition before birth. Death from strokes in elderly are often result of weak brain vasculature developed pre-natally.  Vitamin D and C deficiencies are major risk factors for pre-eclampsia.

B. Nutritional influences on epigenetics and age-related disease
Sang-Woon Choi, MD, PhD, Jean Mayer USDA HNRC on Aging at Tufts University, Boston, MA
Dog, human, chimp DNA sequence and number of proteins are similar; big difference in phenotype is environment in which genes are expressed during birth, especially epigenetics.  Diet may delay aging via epigenetic effects. Can you nourish your DNA? Caloric restriction changes DNA methylation. Hydroxymethylation =OHMe (from oxidative damage from free radicals) increases with age. Ethanol decreases OHMe. But OHMe also decreases in cancer cells.

C. Folic acid deficiency, aortic plaque formation and DNA methylation in vascular tissue
Susan Duthie, PhD, University of Aberdeen, Aberdeen, UK
Dutch Hunger Winter of 1944-45 people survived on 400-800 Cal/day.  Offspring had large  increases in obesity, CVD, and cancer, due to epigenetic changes during pregnancy.  In a twin study where newborns had similar DNA methylation, kids changed methylation patterns due to diet and environment. Saturated fat hurts, polyphenols, MUFA, vitamins B6, B12, C, and folate improve methylation patterns.  More than 100 gene methylations changed in aorta by High fat and folate deficiency.  80% of changes occur in utero, only 20% post birth.

D. Bioactive food compounds and epigenetic mechanisms in breast cancer (BCa)
Donato Romagnolo, PhD, University of Arizona Cancer Center, Tucson, AZ
5% of BCa is BRCA-1 gene, which repairs DNA breaks. Estrogen induces BRAC-1, as does genistein from soy, as does resveratrol, which is good. TCDD is an industrial pollutant found in 4 legged animals which activates the c-myc oncogene.  Sesame oil blocks TCDD.

E. Methylation profiling in breast cancer prevention
Clarissa Gerhäuser, PhD, German Cancer Research Center (DKFZ), Heidelberg, Germany
Hypermethylation increases transcription, occurs with aging and cancer, increases genetic instability.  Natural products which improve DNA methylation include soy, green tea, curcumin, selenium, vitamin A, apple and coffee polyphenols, and butyrate.  Illumina is gene screen that measures 450,000 methylation sites.  Especially hypermethylated causing trouble are homeobox protein genes, and this could be modulated by diet.  BCa genes can be 50% inhibited by genistein/soy, green tea, or exercise!

F. Modulation of microRNA profiles by dietary chemopreventive agents
Alberto Izzotti, MD, PhD, University of Genoa, Genoa, Italy
MicroRNA MiRNA induced by cigarette smoke, changes RNA expression and protein levels.  Chemopreventive agents reduce harmful MiRNAs. These include: carrots, milik, fish, eggs, olive oil.  Procarcinogens include pyrolysis from burnt meat, ethanøl, arsenic, cyanobacteria, bisphenol A (BPA) in plastic, esp. water bottles.  Black pepper increases the bioavailability of resveratrol.

V. HEALTH BENEFITS OF VITAMIN C (AA): BEYOND SCURVY
A. Chemical biology of pharmacological ascorbate to treat cancer
Garry Buettner, PhD, University of Iowa, Iowa City, IA
He has run clinical trial on IV AA for cancer patients, cooperating with Mark Levine at NIH.  Expert on in vivo chemistry of AA.  AA is mainly recycled by glutathione system. It took him 2 years to get IRB approval to run test of IV AA to treat cancer.  Finally approved as a prodrug to deliver H2O2 to tumors.  1mM AA in vitro produces 25 micromoles H2O2 per sec.  20mM AA kills all cancer cells in vitro.  Catalase protects normal cells.In clinical trial, used doses increasing weekly from 15 to 100g, with no adverse effects. At 100g level, dose dripped over 2 hr to prevent osmolar stress.  Patients treated up to 400 days. No oxidative stress in normal cells, just in tumors.Two of 9 pancreatic cancer patients survived at end of trial.  AA appears to be cytostatic rather than cytotoxic to cancer, so it is not just catalase deficiency in cancer cells.

B. Vitamin C (AA) supplementation effects on blood pressure (BP)
Edgar R. Miller III, PhD, MD, The Johns Hopkins University School of Medicine
AA reduces uric acid production, and thus reduces gout.  High serum AA reduces BP.
Reduction of BP by various things: Dash diet -12; vitamin C -2 to -4; fish oil -6; exercise -10.  -3 decreases stroke rate by 10%.

C. Vitamin C in brain development and cognitive function – NOT JUST AN ANTIOXIDANT!
Fiona Harrison, PhD, Vanderbilt University School of Medicine, Nashville, TN
NHANES 2010 shows average intake of AA is just 80-90mg/day.  Those with supplements get 400-500mg/day.  30% are dangerously deficient, especially among the elderly.  Plasma has 50mM, kidney 0.5mM, Cerebral spinal fluid 300mM, neurons have 2-8mM???So AA is very important to brain function.  Transferred across the blood brain barrier by Sodium vitamin C transporter enzyme.  In tests with AA knockout mice, AA dramatically improved memory. Old mice given AA performed as well as young mice on memory and balance (rotorod) tests.
AA is essential to produce neurotransmitters tyrosine to dopamine to  norepinephrine and tryptophan to serotonin.  People with scurvy has lower dopamine and serotonin levels in their brains,  Depression can be helped by AA supplementation.  Vital to fertility  and pregnancy!!!

VI. MICRONUTRIENTS IN FERTILITY AND PREGNANCY

  1. Achieving optimal folate status: why and how, Helene McNulty, PhD

Celiac disease (prevalence 1% in Ireland) causes folate deficiency.  Megaloblastic anemia is caused by folate or vitamin B12 deficiency. Preeclampsia may be caused by folate deficiency.  In fetus/neonate, folate deficiency causes early pregnancy loss, low birth weight, preterm delivery, congenital defects including neural tube, heart, and facial defects.  Women must get 400 mcg daily; after one problematic birth a woman should get 4mg/day during next pregnancy.  Children born with enough have higher IQ at age 6.
Folate deficiency is also involved in cancer, heart disease, and stroke. Enough can reduce BP 8mM Hg.  Folate is best obtained from supplements. In food, it is unstable and not bioavailable.  Europe does not fortify but instructs women  to supplement, but warning is mostly ignored.  Women must begin supplementing pre-conception. Most breakfast cereals are supplemented, but neither Walmart nor Trader Joe’s granola had any.

B. Role of micronutrients in human fertility
Kelton Tremellen, PhD, Repromed, Adelaide, South Australia, Australia
He is an expert in fertility.  7 steps to successful pregnancy, 2 in men.
MEN – 1 in 10 have impaired fertility due to nutrition.  He recommends Menevit or Fertility Blend supplements, which contain vitamins C, E, folate, zinc, and lycopene.  Free radicals cause infertility. Radicals make sperm stiff so they cannot swim, and damages head so they cannot penetrate the egg.  DNA in sperm is packaged 6x more tightly than in nucleus.  Antioxidants double viable conception rate.  Also improves next generation of offspring via proper DNA methylation, blocking DNA damage, reduces leukemia and brain tumors 2 to 3x.
Testosterone is increased in men who get 3,000 IU vitamin D (VD) daily.
WOMEN – 1. Need copper, zinc, for CuZn superoxide dismutase protects the corpus luteum.  VD is very important, and even most women in Australia (high sunlight) are still deficient in VD.  Pre-eclampsia, diabetes, preterm delivery are all reduced by 4,000 IU VD daily. It also increases Testosterone in women, which is important for sex drive.
Sufficient Folate level doubles the rate of twins.
Vitamin B6 and B12 are necessary to reduce homocysteine (HC) levels.  HC is pro-oxidant, pro-inflammatory, reduces beneficial nitric oxide, is a reproductive toxin.
Iodine is essential.
Iron is important, but too much is harmful, causes nausea, constipation, pre-eclampsia.
For women, he recommends One-A-Day prenatal or Pregnacare conception vitamins, but neither has enough VD.

C. Micronutrients and the developing brain
Victoria Hall Moran, PhD,  University of Central Lancashire, Preston, UK
Main periods of synaptogenesis in the brain are 21 to 28 days post-fertilization, 0-3 yrs old for sensory development in the brain, 1-5 for motor development, 3-21 for cognition. Critical nutrients include iron, zinc, iodine, copper, selenium, vitamins A, B, C, D, choline. Iron important for dopamine, serotonin, and noradrenaline. 
IRON DEFICIENT: 20 to 50% of pregnant women; 20% of 1-4 year olds; 12% of elderly; 10% of females; 5% of males
Zinc is 4th most concentrated ion in brain; 17% deficient worldwide; 7.5% in industrialized world; 25-30% in Africa.
Environmental factors during child rearing: breastfeeding increases IQ, brain grows faster; close body contact is essential, produces better stress response in kids. 6pt IQ improvement. Higher socioeconomic status increases rate of breast feeding.
She urges AT LEAST 6 months of breastfeeding.

VI*. ORAL ABSTRACTS
A. Bowman, Omega 3s and white matter in the brain (Study on 85 year olds http://www.ncbi.nlm.nih.gov/pubmed/22205763)
Omega 3 is vital for executive function and processing in the brain.Transfats and omega-6 harm the brain. There are white matter lesions in young people from omega-3 deficiency.  85 yr olds and kids need especially vitamins B, C, D, E, and omega-3 to maintain brain white matter.
Good test (costs $750) is WMS-R logical memory test.

  1. Scholey, Multivitamin/mineral
    Short term memory improves with taking a multivitamin. Blood glucose decreases within 5 minutes when thinking hard, thinking burns lots of calories.

C. Samax – Vitamin C (AA) and inflammation
60 trials show AA decreases the severity and duration of colds. AA has effects on gene expression and inflammation. Immune response is downregulated by AA.

 D ., Vissers, AA in colorectal cancer
Core of tumors is hypoxic. AA decreases tumor grade in colon.  More AA in serum, longer survival of colon cancer patients.  Note Roc’s study shows dosage of AA above 2g/day goes directly to intestine, not serum.

  1. Beaver, Sulfurophane (SFP), in cruciferous veggies/garlic, in prostate and other cancer

SFP is cytotoxic to cancer but not normal cells
SFP alters 3,000 genes level of expression, some increasing, some decreasing.

VII.  by LPI Director, Balz Frei, PhD
Plenary Lecture by Awardee Helmut Sies of Dusseldorf, for his work on selenium and flavonoids.Antioxidants (AOx) are really “bioactives”, involved in enzyme regulation, gene expression, and many processes beyond free radical reduction.  Peroxide radical is present at 10exp-11 M.  Hydrogen peroxide is present at 50 nM, oxygen at 2 mM in peroxisomes, lots of H2O2 present in regenerating amphibian tails.  In 1936 Seyle defined stress. It increases from hypoxic signaling, to redox signalin, to injry and repair, to apoptosis, to necrosis at the most oxidative stress.
A. Szent Gyorgy got Nobel Prize for discovery of AA.  He first called it ignose (ignorant of structure sugar compound), then Godnose, finally ascorbic acid. Photooxidative stress in the eye produces singlet oxygen – main defenses carotenoids, xeaxanthin and lutein.  Polyenes dissipate electron energy as heat. Lycopene is the most efficient singlet oxygen quencher and it protects the skin. Postprandial oxidative stress especially caused by glucose – flavanols are best protection.  A high fat diet shrinks arteries over 1 to 5 hrs, counteracted by polyphenols.  Cocoa dilates blood vessel diameter 2x aiding blood flow.  Cocoa also protects and smooths the skin.  Plasma redox potential falls after meals, rises after sleep, between -73 and -83mV.  It also declines 1mV per year over age 50.  AA may counteract this
________________________________________
VIII. Public lectures
A. Healthy dietary patterns in the prevention of breast cancer and metabolic syndrome
Cynthia A. Thomson, PhD, University of Arizona Cancer Center, Tucson, AZ
Risk of Breast cancer (BCa) is proportional to energy intake.  Low sat’d fat intake reduces risk of BCa by 11%. BCa is #1 cause of death among women 35-55.  Binge drinking increases risk.  Resveratrol decreases risk. Green leafy and yellow/orange vegetables with carotenes and lutein decrease risk 43%, cruciferous veggies decrease risk 52%.  Soy decreases risk. Spices turmeric, onion, horseradish, garlic, and rosemary reduce risk. Consume whole grains, esp. fiber, with goal of over 16g/day.  A weight gain of 21 kg as an adult increases risk 75%.  But lose 20 lbs and risk of metabolic syndrome drops 50%.  Easiest key to weight control is just to read the labels of what you buy and eat. She recommends supplementing with folic acid if a woman if fertile. All should take vitamin D.  In Saudi women not taking vitamin D, rate of BCa increases 6x. 

B. Effects of whole grains and nuts on cardiometabolic syndrome risk factors
Penny Kris-Etherton, PhD
Disease risk in 2011

  1. Ischemic heart disease
  2. Breathing
  3. Stroke

Risk factors
1. Blood pressure above 130/85
2. Smoking
3. Alcohol excess

7. BMI
    12. Low nut and seed consumption
Recommendations for whole grains – 3+ servings daily – refined grains cause weight gain, whole grains promote weight loss, and decrease risk for diabetes and CVD, decrease stroke risk 36%, metabolic syndrome 54%, hypertension 19%, LDL 28mg/dL.  6 servings daily reduce prediabetes 90%.
For Nuts – at least 4 to 5 servings weekly – get 20% of Calories from nuts and your arteries open significantly. Nutrs remove cholesterol from arteries to the liver where it is converted to bile and excreted. They are anti-inflammator.  Omega-6 to Omega-3 ratio is not important as long as you have enough of each.  Vegetable oil is mostly omega-6.

C. Polyphenols and health—More than just a berry good idea
Eric Rimm, ScD, Harvard School of Public Health
Dr. Oz, a thoracic surgeon, started out giving good advice, but wwent commercial and his advice is no longer trustworthy.  Best source of polyphenols is dark chocolate and blueberrie. One piece of dark chocolate daily lowers BP, dilates arteries, decreases CVD.
2-4 servings of blueberries/week decreases tension 10%, diabetes 23%, stroke 5%, CVD 34$. Sources of anthocyanins (great polyphenols): #1. Blueberries (also cranberries?) 2. Grapes 3. Apples 4. Bananas 10. Cantalopes. Cooking degrades anthocyanins.
Put Nestle’s cocoa powder in your coffee. Lowers BP 8pts
There has been no significant difference in cancer rates observed when eating organic vs. standard fruits.

D. An integrative, family-based approach to childhood obesity
David Ludwig, MD, PhD, Harvard University
Obesity has increased from 10% in 1960 to 30% in 2005 for 6 to 17yr olds.  It is transgenerational in effects, has decreased life expectancy in obese by 2-5 years, accounts for 1/5th of medical spending, $170 billion.  About 50% of people are on diets, and 50% of weight lost is regained within one year, almost all within 5 yrs.  The obesity epidemic began in the US in the 1970s, Europe in the 90s, Asia in the 2000s.  Sugar makes you hungry, causes most to eat an extra 700 Calories daily. A low fat diet causes a large drop in resting energy expenditure (REE) so one gains weight.  Best is to avoid sat’d fat, high MUFA/PUFA intake.  A very low carb diet burns 500 Calories via REE, best is high protein/low carb/low sat’d fat diet.  Kids in US on average get only 12 min. of vigorous physical activity (PA) daily, and even 40 min/day had no effect – they must get PA spread throughout the day. For parenting style, authoritative is best, neither strick nor indulgent. He recommends just 1 sweet per week for kids. But by 4yrs old, kids should be on a good fruit and veggie diet for treats.  Note TV causes obesity via commercials kids watch.
THE END FOR THE LPI MEETING 2013.

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