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Linus Pauling Meeting Notes   May, 2009
For active links go to this site:http://www.beloit.edu/nutrition/ln/ln09maylpi.htm
About the Linus Pauling Institute
See the entire program with full names and institutions here.
Below after this 2 page summary is my 6 page summary of the conference.

SUMMARY:
WHY SO MANY NEW NUTRITION DISCOVERIES NOW - Omics approach:  These are the technologies for finding the molecules that exist in our cells:
a. Genomics - can identify 25,000 genes in our DNA
b. Transcriptomics - can identify about 100,000 mRNAs that make cellular proteins
c. Proteomics - can identify about 1,000,000 proteins produced in each cell
d. Metabolomics - can identify about 6,000 metabolites produced in each cell
Current robotic/gene chip technology can run 100,000 reactions per day, determining the variable effects of different levels of nutrients in human cells.

VITAMIN K (the biggest new discovery of this meeting) - Vit K comes from green leafy veggies.  US intake is 70-100 mcg daily, daily value is 120 mcg, have just discovered the true requirement for health is 360 to 500 mcg daily.  (cooked spinach has 888 mcg, but peas have only 48, chicken has 2.) 
Dietary vit K reduces heart disease 50%.  Reduces kidney disease risk.  360 mcg daily reverses aortic and arterial calcification which cause heart disease and high blood pressure. Vit K may remove calcium from ears restoring hearing and sense of balance in elderly. Warfarin is the most prescribed drug and a major cause of heart disease! Warfarin (Coumadin) blocks vit K recycling causing major deficiency.

VITAMIN D - 50% of US is deficient in D. Vitamin D affects depression, preeclampsia, hypertension, immune function . Obesity decreases 45% with vit D! Strength and balance are both proportional to vit D status.  Risk of having a C-section is 400% greater in women with vitamin D deficiency.  Breast milk contains only 10% of vitamin D taken by mother.  Nursing infants need 400 IU daily for full growth, so mother should take 4,000 IU or give baby 400 IU supplement. For psoriasis treatment, treat with vit D in Vaseline on skin.

ANTIOXIDANT CONUNDRUM - media vilifies antioxidants, misinterprets clinical trials.  In fact vitamin E (200-400 IU daily) and vitamin C (nutrition investigator ideal 500 mg morning and night) reduce stroke 42%, Alzheimer's 50%, heart disease up to 50%, cancer up to 50%.

WEIGHT CONTROL - Weight watchers is the only diet that works a little, but a low fat high protein low sugar high fiber diet is best and does lower cholesterol and LDL. US Food supply exploded, from about 2,000 cal per person per day around 1980 to 3,900 in 2000. Marketing food to children is a $7-10 billion annual investment.  Only 23% of grocery products have tolerable nutrition; 80% of that is in fruit and veggie aisles

HEART DISEASE - Fructose, sugar, and starch (carbs except for fiber) cause high LDL, low HDL, high triglycerides, leading to diabetes, heart disease, metabolic syndrome. Statins lower only big LDLs, not the hazardous small LDLs, so statins only reduce heart events by 27%!
See Framingham Heart Study Coronary Heart Disease Risk Prediction Chart. 
To lower risk:
a. Diet high in polyunsaturated fats is best to lower heart disease risk
b. 1-2 drinks of alcohol per day
c. fruit, vegetables, fiber lower risk
d. sugar, meat, butter raise risk
e. fish or 2 fish oil capsules per day - 200 mg DHA daily (1 g fish oil) lowers dementia

RESVERATROL - A low dose of dietary resveratrol partially mimics caloric restriction and retards aging. Expert on gene technology, caloric restriction who lectured us on Resveratrol takes 100mg Resveratrol per day. He also recommends vit. E that prevents transcriptional changes. (go to Nutrition Investigator website for link to legitimate source of resveratrol)

CURCUMIN (in turmeric) restores proper gene expression and lowers risk and impact of emphysema, Resveratrol helps same mechanism.

VITAMIN A - useful during colds after infancy, acts as a transcription regulator.

EPIGENETICS - Epigenetics is the science of DNA and histone labeling by HDACs and methlyating agents, controlling whether genes are expressed. Choline, folate, SAMe are key methylating agents - good for you.  Broccoli and garlic are also valuable in diet for epigenetics, may prevent or stop cancer.

PREGNANCY - Prospective parents must get  choline, folate, even SAMe daily from prior to conception until 7 days after conception when the blastula implantation occurs.  This determines epigentics - gene expression for entire offspring's lifetime. 

HEALTHY BRAIN AGING - Eating fruits and vegetables, and taking  vitamins folate, C, D, and E, and Juvenon (alpha-lipoic acid and N-acetyl-carnitine) have been proven to have a host of benefits: = restores brain functions to youthful levels
improves learning and relieving depression.
prevents cognitive dysfunction with aging
improves both memory and motor speed
allows less fatigue, better mood, less stress
less stroke and better health

ALZHEIMERS - Amyloid-beta (Ab) is marker of Alzheimer's damage in brain. Ab is inhibited by antioxidants. Can predict Alzheimer's now based on tests given at age 16-18! [D. Allan Butterfield-University of Kentucky]
So there's the highlights of the meeting of the Linus Pauling Institute for May, 2009. Remember – you are what you eat! Till next time  ********Doc Roc

END OF EMAIL

FULL NOTES OF MEETING UNEDITED
KEY ARTICLES RELATED TO PRESENTATIONS:
1. Roth GS, Lane MA, Ingram DK. Caloric restriction mimetics: the next phase. Ann N Y Acad Sci. 2005;1057:365–71. 25. Blanc S, Schoeller D, Kemnitz J, ...
2. Barsh & Schwartz, Nat. Rev. Genet. 3 (2002) 589–600
3. Ann Intern Med 142: 56-66 (2005) Systematic Review: An Evaluation of Major Commercial Weight Loss Programs in the United States - http://www.annals.org/cgi/content/abstract/142/1/56 - With the exception of 1 trial of Weight Watchers, the evidence to support the use of the major commercial and self-help weight loss programs is suboptimal.
4. Int J Obes Relat Metab Disord 2000;24:1545-52. Bray G, Popkin BM. Dietary fat intake does affect obesity! Am J Clin Nutr 1998;68:1157-73. Lindstrom J ...
5. JAMA. 2007;297:1376-8. Ridker PM, Cushman M, Stampfer MJ, et al. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men.

HEALTHY AGING: NEUROCOGNITIVE DISORDERS AND
MOLECULAR MECHANISMS
1. Healthspan extension by resveratrol - 100 and 400 mg/kg body weight tested up to mice and fish; up to 2,400 g/kg is safe; has cardio and diabetes benefit, reduces cataracts, protects bones, increases learning - use 40mg dose based on dose/response curve
2. A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice - use 50 mg Res/kg diet = 5mg/kg body weight
Used gene chip for analysis of 45K gene transcripts
Caloric res and Reserv change about 745 genes identically with age
Main supplements maintaining gene expression with age are:
Cal Res, ALA, CoQ, Lycopene, Acetl Carnitine, Reserv
HE TAKES 100MG res/day
Also recommends vit. E that prevents transcriptional changes [http://jn.nutrition.org/cgi/content/abstract/138/6/1010]
Company that manufactures reservatrol properly is resVida from DSM [http://74.125.47.132/search?q=cache:P0-E8zgYtVAJ:www.dsm.com/en_US/downloads/dnpsa/resVida.pdf+DSM+resvida&cd=1&hl=en&ct=clnk&gl=us]

3. Epigenetics, diet, and aging -
Epigenetics is DNA and histone labeling, controlling whether genes are expressed. during conception to 7 day blastula implantation in humans, this determines gene expression for entire offspring's lifetime.  Diabetic mothers produce diabetic children - need folate, SAMe for healthier patterns

4. Alpha-lipoic acid (ALA), N-acetyl carnitine (NAC) and other micronutrients in cognitive dysfunction -   Tested brain function in aging beagles:


Diet

Loss of Brain function vs puppy

Control

75%

Diet enriched with fruits and veggies

20%

Antioxidant diet (ALA+NAC + vit C + vit E)

33%

Antioxidant + fruits and veggies

0% (learn as well as puppies)

[Many of you have heard me speak of Dr. Bruce Ames discovered that ALA and NAC turn old mice into young mice in terms of learning and energy - now a product for people called Juvenon]   He recommends a dosage of 2.7 mg/kg ALA and 6 mg/kg NAC.
Antioxidant, fruit, veggie diet even worked restoring brain function in elderly dogs.  Diet both preserves neurons and reduces amyloid beta of Alzheimer's.
Brain derived neurotrophic factor (BDNF) is protein humans produce linked to improved learning and reduced depression.  Antioxiant/enriched diet restores BDNF almost to youthful levels.

5. Dietary supplements improve cognitive function in humans - Vit C is an important central nervous system antioxidant.  So are vitamins D and A.  B  vitamins beneficial, reducing harmful homocysteine.  Folate improves both memory and motor speed.
A. Did 33 day diet adding antioxidants and vitamins - lesss stroke and better health.
B. Multivitamin/mineral - less fatigue, better mood, less stress.
C. Resveratrol - 250 to 500 mg improves brain blood flow but no performance benefits

6. Oxidative stress and neurodegeneration in Alzheimer's disease - Amyloid-beta (Ab) is marker of Alzheimer's damage in brain. Ab is inhibited by antioxidants. Can predict Alzheimer's now based on tests given at age 16-18! [D. Allan Butterfield
University of Kentucky] So start getting Antiox early to prevent accumulation of damage - noticeable symptoms of AD usually occur at age 70 to 80.

MICRONUTRIENTS AND IMMUNE FUNCTION
7. Vitamin D and immune function - 1 billion worldwide are vit D deficient.  40--100% of US elderly are deficient! vit D required for proper immune function, and is anti-inflammatory like fish oil.  Induces toll-like receptor that kills bacteria.

8. Vitamin A in immune function and infection - vit A is transcription regulator.  Infants especially need vit A from 0 to 3 months.  127 million worldwide are deficient.  Can give 50,000 IU monthly to infants.  Prevents many infections, measles, diarrhea, parasites.

TH2 may cause asthma, high vit A in infants may contribute to asthma by preventing infections.  Take vit A for colds after infancy.  At high levels bad for bone health.

VITAMIN K: NEW FUNCTIONS AND MECHANISMS OF ACTION
Vitamin K (AJCN 69:74-9 (1999) - Low intakes of vit K increase hip fractures about 50%. 1.5 million osteoporotic fractures annually in US costing $19 billion

10. Determinants of vitamin K status in humans - Vit K1 is phylloquinone epoxide. now know high levels (360 to 500 mcg daily) are necessary for carboxylation of vit K-dependent proteins so they can function properly.  Vit K comes from green leafy veggies. Also obtained from Miso, Japanese fermented soy, has lots of vit K2 (best form of K to eat) US intake is 70-100 mcg daily, daily value is 120 mcg, true newly found requirement is 360 to 500 mcg daily.  Note 1,000 IU of vitamin E or excess vitamin A interferes with vit K.

11. Vitamin K: The coagulation vitamin that became omnipotent - K is Koagulation, German, original prime function of vit K.
Warfarin (Coumadin) blocks vit K recycling causing major deficiency.  Warfarin is the most prescribed drug and major cause of heart disease!  - "blood thinner" prevents clotting, thus heart problems, but horrible effects from blocking vit K protein functions. Coumadin treatment causes calcification of arteries and high blood pressure.  Dietary vit K from meat and cheese reduces heart disease 50%.  Reduces kidney disease risk.  360 mcg daily reverses aortic calcification.  Best is vit K2, not K1.

12. Vitamin K-dependent protein carboxylation
16 Vit K activated proteins found recently
Vit K converts amino acid glutamate (GLU) to gamma-carboxlyated GLU (GLA)
involved in blood clotting, hemostasis, calcium regulation (removes calcium from arteries where calcium causes high blood pressure; may remove calcium from ears restoring hearing and sense of balance in elderly)

DIET AND LIFESTYLE IN METABOLIC SYNDROME AND
CARDIOVASCULAR DISEASES
13. Comprehensive metabolic analysis for understanding of diabetes and obesity mechanisms - Omics approach:  These are the technologies for finding the molecules that exist in our cells:
a. Genomics - based on the sequence of human DNA, genomics is the identification of what genes (about 25,000 are likely are in cells that have the potential to produce mRNA to code for proteins
b. Transcriptomics - the identification of what mRNAs (about 100,000 are possible) in what quantity are expressed in cells that has the potential to produce proteins
c. Proteomics - the identification of what proteins (about 1,000,000 are possible) in what quantity are produced in each cell
d. Metabolomics - the identification of what small molecules (metabolites) (about 6,000 are possible) in what quantity are produced in each cell
Current technology can run 100,000 reactions per day, identify 2,000 metabolites easily, find and measure up to 3,500 peaks and compare quantities to standards to find amounts of metabolites in a cell.  It is on this basis that action of vitamins like D and K are being discovered.

14.              Exercise-induced protection against insulin resistance
Insulin resistance correlates with intra-muscular lipid accumulation, but same thing occurs with lots of exercise.  Exercise expresses proteins to utilize lipids properly.  Even with obesity and high fat diet, exercise restores insulin sensitivity.  Key danger is combination of high fat diet and high caloric intake without exercise.

15. Diet, weight control, and metabolic syndrome
Strategy A. Cut calories -Weight programs all fail after 5 years
Ann Intern Med 142: 56-66 (2005) Systematic Review: An Evaluation of Major Commercial Weight Loss Programs in the United States - http://www.annals.org/cgi/content/abstract/142/1/56 - With the exception of 1 trial of Weight Watchers, the evidence to support the use of the major commercial and self-help weight loss programs is suboptimal.
Strategy B. Change dietary composition -
i. low fat diet does not cause weight loss - Int J Obes Relat Metab Disord 2000;24:1545-52. Bray G, Popkin BM. Dietary fat intake does affect obesity! Am J Clin Nutr 1998;68:1157-73. Lindstrom J ... Ad-libitum low fat diet meta-analysis - people lost just 2-4 kg if obese, no  weight loss if not obese.
ii. low carb diet does not cause weight loss - NEJM 348: 2082-90 (2003)
iii. i. high protein diet does not cause weight loss - Int J Obesity 23: 528-36 (1999) - lost weight at 6 mos, rebounded at 1 yr.
Strategy C. Do both A. and B. - NEJM 360: 859-873 (2009) - no effect on body weight, but low fat high protein diet does lower cholesterol and LDL; individual response varies greatly - large genetic component based on twin studies.
High blood pressure sensitivity to salt in 25% of people.  Others no effect of high salt diet.

16.              Dietary and genetic effects on atherogenic dyslipidemia
Human LDL phenotype B causes high triglycerides, low HDL, high LDL. dangerous and 40-70% inherited; low fat-high carb diet induces phenotype B. High fat low carb diet is much healthier.  High saturated fat level causes larger LDL, small LDL is more dangerous to health. CONCLUSION:  Obese should restrict carb intake, esp. fructose.  Atkins is bad, but low sugar/low fructose/high fiber diet is good.

17. Diet interventions for heart disease prevention
Statins lower LDL, but statins only reduce heart events by 27%!  Hazardous small LDL does not decrease with statins. 
See Framingham Heart Study Coronary Heart Disease Risk Prediction Chart. 
To lower risk:
a. Diet high in polyunsaturated fats is best to lower heart disease risk
b. 1-2 drinks of alcohol per day
c. fruit, vegetables, fiber lower risk
d. sugar, meat, butter raise risk
e. fish or 2 fish oil capsules per day - 200 mg DHA lowers dementia
Plant sterols lower LDL 9%.

18. Antioxidant Conundrum  - Jeffrey Blumberg - Tufts
Denham Harman, who developed free radical theory of aging, died three weeks ago at 93.
Finasteride reduces risk of prostate cancer (and slows male pattern baldness and prostate hyperplasia)
Some studies of vitamin E benefit:
  2,000 IU Vit E slows alzheimers
   cuts alzheimers risk 50% (Dunn et al, Neurology, 2007)
   Heart attacks decrease 23-36% with 300 IU vit E/day
    24% reduction of coronary heart disease (CHD) in women
    Stroke decreased 42% (Knekt et al, AJCN 2004)
Problem with most clinical trials  is the subjects selected are abnormally healthy

19.              Dietary HDAC inhibitors in garlic and broccoli - Dashwood
HDAC is histone deacetylase that turn gene expression on and off
Hypermethylation silences genes
Many HDACs in clinical trials for cancer therapy
In diet, butyrate, organosulfur and sulfurophane in broccoli and garlic.

20. Oxidative stress, dietary polyphenols, and epigenetics in lung inflammation
Turmeric spice contains molecule curcumin.  Grapes have Resveratrol.
curcumin restores HDAC and lowers risk and impact of emphysema, Resveratrol helps same mechanism.

21. Epigenetic programming in utero - peri-conceptual methylation
You are what your mother ate.  DNA methylation mainly is of sperm, egg, 7 days after fertilization prior to implantation at blastula stage.  Assisted reproductive technology (ART) susceptible to imprinting disease. ART now responsible for 1 in 100 births.  First paper on imprinting disease BMJ (1990) 301: 1111.
Choline, folate, SAMe are key methylating agents - good for you. 

22. Linus Pauling Institute Prize for Health Research - Dr. Michael Hollick, vitamin D
Vitamin D affects mood, depression, cancer, etc.  750 million years ago first made - oldest hormone?  350 million yrs ago left ocean, still need Calcium.  50% of infants are vit D deficient.  Almost no vitamin D in breast milk.  Infertility may be vit D deficiency.  Periodontitus may be D deficiency.  70% decrease in ability to make vit D at age 70.  Obesity decreases 45% with vit D! 50% of US is deficient in D.  Serum 25 (OH) vit D should be 55 ng/ml.  Among those taking a multivitamin and drinking 2 glasses of milk daily, 48% are still deficient. 
3-6 months of vit D relieve deficiency.  Strength and balance are both proportional to vit D status.
Vit D2 and D3 are equally beneficial; 10,000 IU daily is safe, 2,000 IU daily is optimum.
Vit D makes leukemia cells revert to normal.
For psoriasis treatment, treat with vit D in Vaseline on skin - 92% resolve, 65% clear
1,000 IU daily reduces colon, breast, and prostate cancer risk by 50%.  Risk of all cancers reduces 60%.  Hypertension drops 6mm.  200 genes in the heart influenced by vit D, vit D deficiency increases risk of heart disease 50%.
Sun exposure decreases risk of melanoma.  87% of dermatologists were deficient in vit D when he tested them.  Sun exposure is healthy if no burning.  Most common vitamin deficiency is D!

23. Marion Nestle, NYU Public Health
US Food supply exploded, from about 2,000 cal per person per day around 1980 to 3,900 in 2000.  Because since 1980 shareholders want quick returns on investments, food companies compete to sell food.  Food outside home has more calories. Buffet syndrome - take larger portions. Ubiquity, proximity, and low prices all contribute to obesity epidemic.  Marketing food to children is a $7-10 billion annual investment.
Her analysis: 23% of grocery products have tolerable nutrition; 80% of that is in fruit and veggie aisles.  In UK, they have a traffic light labeling system for food products, green, yellow, red spots, rather than complicated US food labeling of calories, fat, etc.  Her advocacy is now for the Real Foods Movement, food as a social movement.

So there's the highlights of the meeting of the Linus Pauling Institute for May, 2009. Remember – you are what you eat! Till next time  ********Doc Roc

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