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Stavia's report on our meetup in San Diego 2017

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Stavia's report on our meetup in San Diego 2017

Postby Stavia » Fri Aug 04, 2017 6:10 am

Hi team! Waves from San Diego.
Here we are, representing all our members.

PLEASE COMMENT OR CORRECT OR ADD AS YOU WISH

Day 1:
Greeting old and new friends. Thanks to all who travelled here, and who are here with us in spirit.

ANDREAS EENFELDT
Dietdoctor.com
Andreas is a Swedish doctor who started a now very successful LCHF website and online community. He is very passionate about reaching out globally. Nothing really new for us, but its nice to see the situation in Europe.

DR MERCOLA
This very well known health advocate did not fail to entertain but for me his lecture was patchy and disjointed. He bounced around between electronagnetic radiation, nitric oxide and various other topics including lectins, raised ferritin and an infrared machine for $69 that treats Alzheimer's. I stopped taking notes. I guess it's all on his website.

Dr ERIC WESTMAN
He is a practising obesity clinician who uses LCHF as one of his approaches. He shared some of his patient's success stories. Average weight loss appeared to be 13 pounds/patient, when one looks at the numbers. Food diaries of real patients didn't seem to be great food quality. Nothing really new for us. He doesnt favour fasting.

I skipped the next talk.

DAVE FELDMAN
Finally in our private session we had a meaty discussion. Dave shared his n=1 experiments which are all available on his website cholesterolcode.com
Bottom line: his works suggests that blood cholesterol responds in an inverse fashion within 3 days to an abundance or shortage of energy in the form of triglycerides from fat in food. Those who are lean with low glycogen stores will respond in a more exaggerated fashion to dietary fat restriction.as they have less fat and glycogen stores to call on.
He is also not worried about e4s having a higher LDL. He believes the regulatory system sets it at this level to deliver enough LDL particles to the cell receptors.
Fascinating stuff.
He promised to share his PowerPoint, but we will also have the video to share with you later.


edit: link to videos of our evening discussions with our guest speakers
viewtopic.php?t=3383

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Re: Stavia's report on our meetup in San Diego 2017

Postby Stavia » Fri Aug 04, 2017 10:58 am

Day 2

GEORGIA EDE

Fabulous lecture. Lovely summary of glucose metabolism in the brain. Ketones can only provide 75% of cerebral energy requirements. GLUT-1 transports glucose across the BBB and GLUT-3 into the cells. Neither are insulin dependent.
But there are insulin receptors in the amygdala, hippocampus and cortex (mood, memory, cognition). Insulin is a growth hormone, regulates energy balance, cell growth and survival. It crosses the BBB via insulin receptors but only up to a threshold. This is in contrast to glucose which is always ~60% of blood glucose with no upper limit.
The BBB can become insulin resistant this creating a reduced intracerebral insulin and hence glucose metabolism availability despite raised cerebral glucose Excess glucose but insulin deficiency results in depletion of glutathione, increased free radicals, AGEs, reduces nerve conduction speed and reduced growth factor.
This is called " cerebral glucose hypometabolism".

Of special note is that the hippocampus has GLUT-4 receptors which are insulin dependent!!

Georgia terms the hippocampus "fragile" - with its higher glucose demand, its highest concentrator of insulin receptors and ability to generate stem cells.

How do we know for sure that IR is a cause of AD?
1. 80% of AD have IR or T2DM
2. people with AD have reduced insulin in their brains
3. insulin reduces amyloid aggregation in vitro
4. insulin regulates phosphorylation of tau in vitro

Why doesnt everyone with T2DM get AD and vice versa? There seems to be individual variation in what the final outcome of IR is - it can be PCOS, AD, CVT, T2DM, renal or eye toxicity etc
But overall - IR is NOT GOOD.
Remember, glycaemic control trumps lipids!! Every single time...


DOM D'AGOSTINO

Very complex nerdy sciencey discussion of extreme conditions eg compression, deep diving, altitude, 100% oxygen supplementation and ketones. This is very much cutting edge extreme experiments and he is focused on artificial ketone esters. It appears that ingestion of ketones esters reduce blood glucose!! Not sure of the mechanism.
He has also been studying these in rat models of seizures (really important in deep diving!) and TBI.

There was a throwaway comment that he has noted in AD there is a rate limiting deficit in pyruvate dehydrogenase activity (citric acid cycle which eventually generates ATP) which can obviously be bypassed by ketones. (I found this https://www.ncbi.nlm.nih.gov/pmc/articles/PMC39697/)

He showed a graph of brain fuel in the fasted state: about 1/3 glucose, rest ketones (mainly Beta hydroxybuturate and some acetoacetate). Similar to Georgia Ede's 20% ish glucose required for the brain. (obviously can be generated by hepatic gluconeogenesis, doesn't need to be eaten)

One sentence summary: ketone esters can protect against major oxidative stress.


JEFF VOLEK

Interested in ketosis since the 80s. Primarily initially for athletes and he didnt predict it would have wide application. We now have athletes competing in ultramarathons and tour de france etc.

Ketosis is a natural process. Fuel for brain during famine - brain can't use long chain fatty acids. All extrahepatic tissues can use them.
When you are in nutritional ketosis for months to weeks you become "keto adapted". Here you can oxidize fat 2x. Ketones are also signalling molecules - less ROS, less insulin activation etc. Lots of very positive effects.

Image

nothing really new, just a privilege to hear the guru in the flesh. I am really looking forward to Phinney tomorrow.


LUNCH WITH IVOR CUMMINS AND JEFF GERBER

This was difficult to summarise in text, we will put the audio on our site later.

We discussed the relevance of raised LDL (and LDL-P) in the absence of IR. Ivor questioned the evidence around the effects of pure saturated fat (without the associated protein) in e4s. We discussed the role of inflammation overall, as well as gut signalling. We discussed finding common ground amongst those who make difference dietary choices. We also discussed how far to take biomarker testing - is more better?
There were many more questions than answers and we had a lively discussion.

GARY TAUBES

The usual story of the epidemic of T2DM and the blindness of WHO etc to the elephant in the room - the simplest possible explanation is sugar. This was the theory in 1913, 1924 etc......Until Joslin in the US didnt agree - his reasons were -Japanese experience with lots of rice and low diabetes - sugar was needed for hypoglcaemic episodes caused by insulin - most diabetes was caused by eating too much or excercising too much and getting fat.....which moved to "people get fat because they eat too much fat". This then moved to "calories in - calories out" and ended up with "no bad foods only bad behaviours".

However: foods can be isocaloric but not isometabolic....hormonal responses are completely different.

etc etc....you can read his books....we all know the story...

PRE DINNER
MARY KAY ROSS

CIRS is chronic inflammatory response syndrome - caused by environmental toxins (pollution, personal care items), biotoxins (mould, algae, some foods, lyme disease) and heavy metals.

"aerotoxic syndrome " -rush hour, jet plane engine emissions -is this like tobacco where there is no safe threshold?

apoe4s do worse with pollution - increased resultant oxidative stress.

biotoxins are small toxic particles released by biological agents - mycotoxins are nanoparticles and penetrate the BBB easily and create a strong inflammatory response. (mould, dinoflaggelates, actinomyces, algae, cigautera toxin, brown recluse spider bite)

Dr Shoemaker defined CIRS as a multisystem illness caused by exposure to biotoxins - there is a definite HLD susceptibility and this determines the expression of the reaction. Cytokines, MMP9, TGF beta1 and C4a are all involved. The brain and specifically the hippocampus are danaged (reduced hippocampal volume) and leptin resistance is involved.

The symptoms include sleep disturbance, chronic pain, GI issues, prolonged viral illnesses, changes in cortisol, reduced androgens, reduced ADH, MARCoNS colonisation of the nose.

Image

Bredesen and Mary Kay are now seeing this pattern in 65% of cognitively impaired patients. It all depends on how good a detoxer one is, if one is affected or not. Exposure appears to be cumulative over the years.

Management: get out of the mouldy house, binders (eg cholestyramine, apple citrus pectin , treat MARCoNS, VIP nasal spray.

Prevention: clean diet, keto, be mindful of chemical use, manage stress, balance hormones, exercise, sleep, ramp up detox, listen to your body and consider toxins as a cause of symptoms.

DALE BREDESEN

AD is the area of greatest medical failure. Neurologists are very good at diagnosing but not so interested in treating.

How do we lift the "fog" of 20th century medicine?
Why is there a fog?
1. there are only tiny data sets for us as exceedingly complex organisms. Dale feels Occams razor is a false paradigm and chronic diseases are more "Occams network"
2. we are looking only for monotherapies. AD is not like pneumococcal pneumonia.
3. non physiological therapies are used, wrongly
4. we are waiting for symptoms to occur before treating.
5. we are calling the only effective treatment for AD "alternative"
6. we are teaching medical students 20th century medicine
7. we are forcing patients to accept ineffective treatments with side effects

In the 20th century medicine was "what is this?". in the 21st century it should be "why is this?"

Just like osteoporosis with an imbalance between osteoblastic and osteoclastic activity - AD is an imbalance of synaptoblastic and synaptoclastic activity. We need to shift the balance to a more healthy state.

There appear to be three major groups of patients who are cognitively impaired.
And one overlap.

Type 1: inflammation (classic IR and other causes of inflammation)
Type 2. Withdrawal of trophic support eg low T3T4, B12, sex hormones etc
Type 3: exposure to toxins (Mary Kay Ross's presentation)
Type 1.5: Glycotoxic.

Features of type 3 - <65, often at menopause (the reduced bone mass dumps mercury that was stored), often apoe4 negative, defects in organisation calculation visual perception (mainly parietal lobe rather than hippocampal), negative family history, low trigs and zinc, HPA axis dysfunction, exposure to dementogens (mercury, mycotoxins, parraffin candles , formaldehyde, world trade centre blast debris), exacerbated by stress.

There is a potential relationship to Lewy Body Disease.


DINNER and SLEEP!

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Re: Stavia's report on our meetup in San Diego 2017

Postby Stavia » Sat Aug 05, 2017 10:08 am

Day 3

SARAH HALLBERG

One third of Medicare dollars spent in diabetes.
American Diabetes Association standard of care: nothing about reversing the disease. Dismisses low carb. Does not honestly represent the literature.

Sarahs recommends less than 30gms total carbs. Non starchy veggies, nuts and seeds, limited berries, dairy. No grains potatoes or sugar. Adequate protein. High fat including sat but also monos.

Keto works fast in T2DM and has sustained benefits. Trials show it is not only the weight loss that is responsible for improved glycaemic control.
Continuous glucose monitoring is going to be the future of studies.
A metabolic ward study from the 70s looked at nitrogen balance - but look at its findings re hyperinsulinaemia! What a shame it was forgotten.

Image

By giving extra insulin to diabetics - they are medicating their food not their illness!

However: there is an entity called secondary pancreatic failure in long standing T2DM - where the pancreas simply cannot produce enough insulin even for LCHF and wake at levels of 200 and don't drop during the day - in this situation Sarah recommends a small dose of long acting insulin at night so that the patients start at a decent fasting glucose in the morning.


Sarah's blood glucose targets: 120 to 180 in first couple weeks while still on sulfonyureas or insulin.
When off meds : target 140 or less. She wants normalised blood glucose.

Sarah's approach to lipids: makes no decisions based on LDLC which we all know is irrelevant. She feels apob is an area of controversy and feels a skyhigh ldlp or apob may be a trigger for a discission around and decision to use a low dose statin




MIRIAM KALAMIAN
Her area of expertise is keto for cancer but today her topic was:
Variations in blood glucose:

The bogey man of hypoglycaemia - in the keto world people tolerate "low" blood glucose. Medical guidelines say less than 70 is hypoglycaemia but this may go much lower when in ketosis.

Troubleshooting raised blood glucose:

1. Normal variation - large spread of levels with same meal!

2. Circadian rhythm of cortisol: 6-8am peak results in the dawn effect.

3. Luteal phase of menstrual cycle - rise in glucose ? some insulin resistance in luteal phase?

4. Physiological insulin resistance - is this a thing? Miriam feels it is real. As one keto adapts, muscles get better at burning fatty acids and spare the glucose. Also because circulating insulin is low, it takes longer to clear the glucose from overnight gluconeogenesis.

5. Age has a huge effect on metabolic flexibility. Older adults have less flexibility and their blood glucose wont drop as much as younger people.

6. Hidden carbs. Protein. Both raise glucose. Too much protein will affect next day's fasting blood glucose.

7. Meal timing: too many snacks. eating too close to bedtime. Go too long between meals. (women dont do as well with intermittent fasting)

8. there is a goldilocks calorie zone. Calorie restriction not good in cancers.

9. Fibre - friend or foe? it does slow the glucose rise but it the glucose will still rise. Artificial fibres may sequester minerals.

10. alcohol: once keto adapted - can try small amounts.

11. caffeine: individual variation in response.

12. lifestyle: stress!!

13. circadian rhythm

14. social environment

15. physical activity - need to start slow when ketoadapting.

16. meds - steroids , high dose niacin

17. illness, inflammation.

18. check your strips are not expired or contaminated!

19. remember there can be a huge error (20mg/dl) in the readings. If a reading doesn't make sense, repeat it.

20. low haematocrit gives spuriously high readings.


NASHA WINTERS

I missed this but heard the questions : her topic was keto for cancer

1. she uses Longo's fasting protocol for getting patients deeper into ketosis

2. she only uses ketone esters as an adjuvent, not as a quick fix

3. a member of the audience asked about breast cancer - she answered that its everyone's choice but she would recommend always looking at personal factors.

4. she feels frequent radiation is not good in BRCA patients. She believes BRCA is a methylation problem.

5. keto for glioblastoma is where most of the research is. Not much research for other cancers.

6. not good evidence in the studies that suggested breast cancer was driven by dietary fat.

7. studies show that keto plus chemo is more effective. Enhances therapies and mitigates side effects.

8. What about cancer suffers who struggle to eat? There are liquid ketogenic diets. Charlie's foundation. Miriam's book.

9. selenium deficiency is important in BRCA. Be careful with iodine - can precipitate hashimotos.

ALISON GANNETT

she wonders if the overtraining contributed to her brain cancer. Plus she was vegan carbaholic...
haemangiopericytoma. Given a year to live.


Important to look at root causes. Customising cancer is not one size

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She recommends cronometer for tracking. She eats 300gm to 350gm fat a day.

Excercise: under and over are both a problem.

Vit D crucial. She was born with a deficient receptor. She also has methylation problems.

Stress response drives up insulin and blood sugars.

Toxic burden: only drinks filtered water. Small exposure affects her bloods.

Eats nutrient dense food. Need micronutrients for cancer.

Excess iron is an issue.

ROB WOLF

ketogenic diet for traumatic brain injury (TBI)

TBI might be from a 1. focal point of damage or 2. diffuse axonal injury due to acceleration/deceleration shearing forces.

event sequence: primarily - decreased cerebral blood flow - decreased glucose substrate delivery - iscahemic like environment - increased lactic acid - substrate depletion - decreased atp - loss of membrane potential - cerebral oedema

now get secondary insults - membrane depolarisation - "last stand" excitatory neurotramsmitter release - ROS - apoptosis

its basically hypoperfusion then reactive hyperperfusion and then an ischemic reperfusion injury


Rob wonders if a population that is sleep deprived, disturbed circadian cycles, eating MREs -ie soldiers - have worse effects of head injuries.

effects of TBI:
sleep disturbance
cognitive impairment
mood alterations
hormonal dysregulation - hypogonadic

Is there a better way to manage TBI?
1.ketones in the acute phase to bypass the TCA cycle? only other option is to raise glucose sky high.
2. sleep deprivation has a neuroprotective role in the acute phase - hormesis upregulating protective response? but after the first 48 hrs sleep and restoring circadian rhythms is crucial in recovery.
3. MCTs and ketone esters - might be beneficial in the acute phase
4. high dose fish oil might be useful in the early phase (10 to 15gm)

case study: recurrent MMA boxer: glycolytic work triggered syncope and seizures: this happened because his blood glucose dropped during heavy muscle training below a threshold that his damaged insulin-resistant brain couldn't tolerate a lower blood glucose. put him on modified keto diet. 63% fat. 9% carbs (50gms). 28% protein. MCTs delivered part of his calories. he significantly improved, able to do glycolytic exercise, reduced meds significantly.

Potential:
cross over to Parkinson's, AD - commonality is mitochondria. He sees overlap and common mechanisms.

Role of modern life
1. sports and warfare is harder, faster, more frequent
2. kids fed carbs ++ before and during sport
3. modern diet is clearly inflammatory
4. circadian rhythms broken
5. D3 low
etc etc etc


Questions:
1. use in PTSD? not Rob's field
2. there has been some use of a ketone solution in acute TBI rather than Ringers lactate but it hasn't had traction
3. is there benefit in keto in late stages of TBI? yes he feels there is benefit in ketosis years later which may support any healing potential of the brain.
4. pregnancy? children? Rob sees no problem with keto in either. Great evidence with T1DM kids on keto.
5. post stroke: good research with keto
6. how do we make this approach mainstream? keep the conversation going. trench warfare. slow inching ahead and committed to the long haul.
7. is this applicable to other hypoxic acidotic events in ICU like cardiac arrest and sepsis? nobody doing this yet....they should be
8. marketing ketone esters as weight loss gives them a bad rep whereas we should be focusing on their therapeutic effects in disease.
9. mood is better off carbs
10. beta hydoxy butyrate is the activating factor for BDNF!!


STEPHEN PHINNEY

The legend! what a treat!

We are still dogged by the stigma of medical school teaching that diabetic ketoacidosis is fatal...so most physicians do not understand the difference between physiological and pathological ketones

nutritional ketosis: superior energy supply AND
hormonal activity regulating oxidative stress and inflammation

stored energy = eg one molecule of palmitate ->>
usuable energy= 4 molecules of beta hydroxy butyrate (BHB)

the human brain can readily utilise BHB and acetoactate - but about 30% glucose dependent. Is the latter a mechanism for using up the products of glycerol and protein breakdown so we don't become hyperglycaemic?

infants spend their 1st year in ketosis if they are breastfed.

Range: optimal zone nutritional ketosis >0.5mmol/l to about 3mmol/l. fasting goes above 3mmil/l. acidosis only happens at 10 mmol/l or above.
Even at 0.5 BHB is a powerful gene expresser signal.

So...what to eat?

moderate protein (need to look at gms/kg), less than 20% carbs

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saturated fat is it dangerous?:
on high saturated fat diet, blood saturated fat levels are in fact lower: with ketoadaption, saturated fat burning doubles. fat oxidation ramps up ++


a ketogenic diet is anti inflammatory:

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BHB reduces oxidative stress:

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nutritional ketosis increases longevity (with sparing of physical strength agility etc) by 13% in mice (and 26% in nematodes) ....watch this space....


1976: first paper showing reversal of T2DM on ketogenic diet (in a metabolic ward) (7/7).

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2005: lower glucose with lower insulin! this proves insulin sensitivity has improved - confirmed with eugkycaemic clamp.

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the many benefits of BHB

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summary:

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questions:
1. ?tips: count carbs. protein in moderation. eat fat to satiety. need potassium - eat real food not processed meat. 3 to 5 servings non starchy veggies. 5gm of sodium = 12 gm of salt a day. In nutritional ketosis there is accelerated sodium excretion which has a flow on effect (he feels this is mislabelled as adrenal fatigue)
2. dietary fat doesn't drive ketones - carbs and protein do - as we age we tolerate carbs less
3. he uses total carbs not net carbs.
4. it may take months to ketoadapt and to upregulate the relevant enzymes.
5. is there enough fibre for gut health and the microbiome? no real answer.
6. if one wants to be very accurate : when people are in a weight loss phase one should factor in the body fat they are burning in their total fat intake.
7. optimal protein intake - 1gm/kg lean body weight.
8. is there osteoporosis data? : Phinney doing studies on bone density, menstrual function, sleep apnoea.
9. shouldn't reduce protein when body is under stress because body has an increased requirement. can reduce carbs when under stress because cortisol will impair carbohydrate metabolism.
10. magnesium depletion causes cramps, twitchy muscles and hyperreflexia.

GEORGIA EDE before dinner chat:

1. vegetarian as a young adult, put on weight during medical school. tried many diets unsuccessfully. even put on weight on Atkins. Learned protein limitation from Ron Rosedale and that worked for her. And then Gary Taubes book Good Calories Bad Calories. She also has had multiple food sensitivities which she identified and ended up with a mostly animal diet. She was suprised that her brain functioned so much better.

2. There is a dearth of research about diet and mental illness. But there is enough evidence about diet and AD that informs us about brain function. For instance we have mechanisms and trials to show how important IR is.

3. Wants to help the public with nutrition and mental health. Website with her blog.

4. She is wondering from first principles - why would an ancestral gene make it difficult for us to process saturated fat? It doesn't make sense to Georgia. Are there any clinical studies?

5. Dairy fat? Very complex area...
Milk has fat/ lactose/ casein and whey protein - she is suspicious of the protein. Humans dont have the enzyme to digest casein. Whey is a growth hormone. The fat also has active hormones.
Might be worth testing e4s on and off dairy to see if it is a problem for us individually.

5. There are many neurological diseases that have a psychiatric co-morbidity .... like Parkinson's and depression - what if its actually one disease?

Conversely psychiatric issues can develop to have neurologic issues eg bioplar disorder can have cognitive deficits. They also may meet criteria for ADHD.

Psychiatric and neurological diseases may be diverse manifestations of a root cause eg IR.
Trials show that IR may be playing a role in treatment resistant depression....
what if all psychiatric and neurological disease is all the same thing? just different manifestations of IR?

7. does poor eating drive social isolation? no answer but good question.

8. some statins cross the BBB (simvastatin) . The brain makes its own cholesterol which is crucial - its clearly not good to stop the brain making its own building blocks. HMGCoA reductase is turned on by insulin. So lowering insulin can reduce HMGCoA reductase and hence reduce LDL.

9. Reports of glycaemic dysregulation producing anxiety and agitation eg sugar cola kids have spikes in blood adrenaline.

10. diet in ADHD - it does respond to a better quality diet. could be food sensitivities. could be glucose dysregulation. not everyone does well with methylphenidate (anxiety, tolerance, insomnia) and dietary adjustment is an option.

11. is there a test for brain IR? the body IR status should be indicative of brain status. she isnt sure of the evidence of this.

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Re: Stavia's report on our meetup in San Diego 2017

Postby Julie G » Sat Aug 05, 2017 10:15 am

Stavia, I'm loving your summaries! Huge thanks for your efforts here ❤️

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Re: Stavia's report on our meetup in San Diego 2017

Postby lol » Sun Aug 06, 2017 7:35 am

Huge amount of work, Stavia. It will take me a while to sift through it all, but I will.

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Re: Stavia's report on our meetup in San Diego 2017

Postby Gilgamesh » Sun Aug 06, 2017 7:57 am

Stavia, thanks for the invaluable effort! Almost feel like I'm there.

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Re: Stavia's report on our meetup in San Diego 2017

Postby Stavia » Sun Aug 06, 2017 11:35 am

Day 3
DWIGHT LUNDELL
endothelial dysfunction

Dwight is a cardiac surgeon

to a man with a hammer everything looks like a nail. to a cardiac surgeon everything looks amenable to bypass surgery.

The bypass machine can have side effects - cognitive issues - so local stabilisation devices were developed that obviated the need for stopping the heart beating.

Then Dwight realised that he was winning battles but losing the war. He began to believe that CVD was a nutritional disease. He wrote a book and went on public media and spoke against the status quo. The medical board then did some case reviews and revoked his medical licence. He sees it as a badge of honour.

Long story about his iron man prowess and his clear angiogram and zero coronary calcium score.

Endothelial cell
1. barrier - lets things thru selectively - hydrostatic pressure, osmotic pressure, active transport and passive diffusion
2. blood flow: endothelium controls resistance hence blood flow
3. blood clotting
4. repair and angiogenesis


Image

1999: we began to see that CVD is an inflammatory disease

with inflammation, adhesion molecules are expressed by endothelial cells and attract monocytes. these are then converted to macrophages by action of cytokines. macrophages migrate into subendothelial space and if they encounter oxidised and glycated ldl they engulf these particles and die and this causes foam cells and later fatty streaks in the vessel wall. the body will try and heal this with fibroblasts and then this calcifies. in the presence of continued inflammation this will grow.
If the lipid core ruptures: it will cause a clot to form which can completely close off the lumen.

If one analyses patients with MI - over half do not have raised LDL as per guidelines. Should we use risk calculators?

"A correlate does not a surrogate make"

.....then he spoke a lot about statins, but changed some of the facts to make statins appear more dangerous than they are. It was 10 minutes of statin bashing.....(I am not saying I am pro widespread use of statins, I just get extremely annoyed when speakers misrepresent the evidence to make their theory appear stronger)

For instance he stated "30% of people on statins develop diabetes " .
Here is the meta analysis which does not show this. It is much more nuanced. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156828/

He also stated that the PCSK9 inhibitors do not reduce CVD events. Here is the trial results which does not say this. There was a reduction in CVD events from 11.3% to 9.8%
http://www.nejm.org/doi/pdf/10.1056/NEJMoa1615664

Ok onto endothelial injury:

insulin resistance, hyperinsulinaemia - increased vascular permeability, increased vasoconstriction, increased platelet aggregation.


Image


questions
1. what does he feel about framingham? he thinks its flawed
2. does he think there are any benefits whatsoever to statins independent of their lipid lowering effect? answer: even if it does lower inflamnation, shouldn't we be looking at why there is inflammation?


JEFF GERBER and IVOR CUMMINS

Framingham and the muddy waters

funded by David Bobbett


apply engineering methods to medical condition....Ivor had raised Ggt and ferritin. His doc could only offer reducing alcohol, possible haenochromatosis, healthy whole grains....went to three doctors and got the same story!

So Ivor went fishing: need 2x risk in studies to be significant. he found ggt hugely increased risks for cvd and diabetes. then he found ferritin also increased risk of cvd.
then he discovered metabolic syndrome. and he hypothesised that ferritin and ggt were excellent markers of metabolic syndrome.
He realised he was eating far too much carbs and switched. After 8 weeks his GGT and ferritin plummeted. BP dropped before the weight dropped.

Then he asked why couldnt a doctor tell him this??? because status quo cant go back...


Dayspring and Framingham study suggests that LDL less than 200 to 300 irrelevant in prediction of CVD.


Presence or absence of obesity can be anywhere on the spectrum if IR

Image

how do we fix this?
Its not all carbohydrates.
It can also be for example Lipopolysaccharides from leaky gut. Other personal causes of inflammation are possible.

1. eliminate refined carb, processed food, vegetable oil
2. low carb, healthy fat, high quality protein
3. sun, stress, sleep
4. exercise
5. fasting
6. supplements magnesium potassium DHA etc

What your doctor should know but doesn't!
Dr Kraft realised that insulin resistance predicts CVD. He identified 5 patterns in a 5 hr insulin tolerance test

Catherine Crofts in her PhD identified from his work that a 2hr insulin test after a glucose load is a good easy measure of insulin sensitivity. less than 30.

Framingham distraction:
they tracked cholesterol, smoking, hpt, diabetes - but it didnt accurately measure insulin resistance.

Mechanisms for metabolic disease
-> inflammation, oxidative stress and advanced glycation.

Diabetes is a vascular disease. Conversely vascular disease is overwhelmingly IR.

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Coronary calcium score

The calcium is not a risk factor - it is actually the disease.

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Coronary calcium score versus Framingham

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Coronary calcium score progression: increase less than 15% / yr collapses the risk.

US healthcare politics: its a system built on sickness. Change is going to be very difficult to bring about policy change.

questions
1. is the radiation of the coronary calcium score a problem? radiation about the same as a mammogram
2. glucose challenge is not accurate in someone on low carb
3. ggt is a good measure of adherence to diet
4. if someone already doing everything right is a coronary calcium score necessary? possibly not. but its really important for the middle risk masses who need a push to change. and even in those already low carb it may show that there are other issues eg heavy metals
5. BP: some idiopathic hpt may be linked to hyperinsulinaemia. UVA causes vasodilatation.
6. reversing coronary calcium scores? is it possible? answer: reversal is controversial. William Davis has published a small series. No other evidence.
7. supplements k2? Answer: k2 might slow calcification but only associational studies no RCTs.


NICOLAE WORM
fatty liver disease
also known as NAFLD
non alcoholic fatty liver disease

how do we produce foie gras? by "noodling the goose". today without forcefeeding its done with high fructose corn syrup!

NAFLD is an independent risk factor for metabolic disease

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Diagnosed: ast alt ggt, u/s, fibroscan, CT, etc - all not very sensitive.

He uses a risk calculator:
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prevalence:
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The old textbooks say diabetes -> NAFLD but in fact it's the other way around!!

pathogenesis:
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pathways to NAFLD:
(point 2: more than 60gms fructose or sucrose)

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exercise and NAFLD
we need exercise to use glycogen stores, excess glucose - de novo lipogenesis - stored in liver
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after a few days of inactivity our muscles become insulin resistant.

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a pathological rise in insulin activates transcription factors that turn carbs into fat
(de novo lipogenesis)

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confirmed by Berkley study
NI =normal insulin
HI=high insulin
independent of obesity
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It is now established that de novo lipogenesis is a distinct characteristic of IR.


there are dysfunctional adipocytes in NAFLD.
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dysfunctional IR they get inflammed and can't expand and excrete inflammatory cytokines then ectopic fat (no longer only subcuraneous) occurs.

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IR is independent of obesity
black spots on the right are macrophages

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right hand side says: lipid overflow - ectopic fat
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its probably the lipid overflow that is the problem: its the fat in the organs
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ectopic fat and CVD risk

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its the ectopic fat thats the problem

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one may not be obese and have ectopic fat- like women with lipodystrophy who can't store subcutaneous fat. they store fat in their viscera. Also TOFIs.

Its not enough to look at BMI or waist:
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this guy has the highest mortality:
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Metabolically healthy people store their fat subcutaneous. Like even sumo wrestlers who do heaps of exercise.

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main message
fatty liver is both a sensor and cause of IR
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hypothesis that fatty liver and fatty pancreas are the main causes of diabetes.

in the presence of IR, hepatic gluconeogenesis is not switched off by eating and subsequent insulin spike.

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when the pancreas gets fatty, the alpha and beta cells become insulin resistant.

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Therapy for NAFLD

no drugs.
only lifestyle modification

most of the liver fat is from dysfunctional adipocytes (the 59% in the slide)
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exercise - multiple pathways

Newcastle study : reversal of diabetes
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as the liver fat reduced, so did the hepatic glucose production and the fasting glucose

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as the pancreatic fat reduced, the insulin production recovered

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obesity is not an accurate marker. It is the ectopic fat that matters. everyone has a personal fat threshold

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keto in NAFLD

been a few small studies.
Eric Westman
Spanish study
Browning study

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hepatic TG reduction was greater in the keto diet altho same weight loss
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Kirk study
2 days and 2 weeks
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then he ran out of time ***** and went to his last slide:.

**** I am photographing the next slides from my computer a week later:

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****** this is where he resumed talking
-omega 3s block de novo lipogenesis
-polyphenols help oxidize fat in the liver and reduce inflammation
-soluble fibre might be helpful


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******I added this section a week later once I had access to the slides


PETER BALLERSTAT
The secret of the ruminant- we've all been fed a lot of bull

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grass fed vs conventional beef doesnt make an appreciable difference to omega3s

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how much salmon would you have to eat to balance omega6s in vegetable oil.
(soy is really bad!)

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what about hormones in non grass fed beef?
not appreciable

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antibiotic use for weight gain in beef is outlawed a year ago.
hormone use in poultry and swine was outlawed decades ago.

Questions: Peter's opinion
1. shopping should be in line with resources esp when there is so little evidence that it's necessary to buy grass fed meat.
2. grass finished vs grain finished - no appreciable difference in safety or effect
3. GMO vs alfalfa: in a ruminant animal all the nitrogenous material is degraded in the rumen to carbohydrates.
4. pork eggs chicken - he has no concerns about these. flesh from poultry or pork will always have a higher omega 3 content than beef.
5. liver - he has no opinion with grass fed vs grain fed.
6. oestrogen sensitive breast cancer - what about the hormones in the milk/cheese - he admits there is a higher concentration of oestrogen in milk than there is in meat (natural in the case of milk, not implanted as in steers that are for slaughter). He also repeats that soy is worse
7. processed meats.....are they toxic in themselves? or is it what they are served with?

ANTONIO MARTINEZ

avenues of political action
how do we get the message out?

Nutrition Coalition:
committed to changing the guidelines at local, state and national levels.

The current policy is based on association and correlation.
They have 11 evidence based reforms for the US dietary guidelines.

1. to let America know that low fat is no longer recommended by the dietary guidelines (its quietly gone but not announced) and to let Americans know that diet is associated with dyslipidaemia
2. lifting caps on saturated fats - no effect on CVD mortality
3. offer low carb diets as a viable option for fighting chronic disease. expert committees have never systematically reviewed the large body of evidence on low carb trials
4. offer a meaningful diversity of diets which are also individually and culturally appropriate
5. the current DGA diets are deficient in potassium, vitd, vitE, choline. they also heavily rely on the fact that the grains are fortified to reach targets
6. stop recommending only aerobic exercise. muscle training is crucial for insulin sensitivity
7. stop recommending lower is better for salt.
8. stop telling people calorie in calorie out is what its all about. Maintain weight loss by reducing calories and increasing exercise oversimplifies the issue.
9. stop recommending industrial vegetable oils for health. trials show no reduction in cvd mortality but in some trials showed increase in mortality from cancer and suicide
10. stop recommending low fat/lean food alternatives.
11. dont issue population wide guidelines based on weak observational data. the guidelines should be based on rigorous RCTs.

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PANEL : QUESTION AND ANSWER SESSION

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1. Delegate was watching Ivor on YouTube talking to Georgia Ede - Fat Emperor - is there a requirement for fibre in the diet?

Georgia has a video on her website - Pulp Fiction. She also spoke to Ancestral Health 2013 on this - it is on Youtube
She feels there is no evidence for fibre in the diet.

Ivor cited a study on constipation and fibre - background there is no published literature on positive effects of fibre - In this study the patients removed fibre and 100% improved - 3 days between movements to 1 day between movements.

There may be some evidence around glucose absorption.

There may be benefits for gut bugs.

Political aspect: There is unfortunately now a recommendation to eat fibre and an industry built around this.

2. does the butyrate in butter reach the colonic bugs?

I couldn't hear the answer

3. Sprouting and fermenting grains/legumes - does it improve the quality?

Georgia: it does reduce the lectins partially but she doesn't know about the carbohydrate content.

4. Political question:
should we be simplifying the new guidelines - less carbohydrates, real food, dont fear fats, avoid industrial seed oils?

Antonio: Coalition rather wants a variety of approaches available rather than oversimplifying because they are worried about another rabbit hole.

Jeff: feels we should target the 2020 guidelines politically

Ivor: wants to create chapters of a global organisation around the world stacked heavily with medical people

5. vegetables: what would happen if people ate no vegetables?

Antonio: There are some zero carb people that thrive. Sean Baker for instance.

Georgia Ede agrees that animal foods can provide all micronutrients but conversely if one is insulin sensitive carbs may be well tolerated. Amber O'Hearn. Stephan dude in Arctic Circle.

Ivor: some cruciferous veggies may be useful so he is hedging his bets.

Andreas: feels veggies are important for sustainability of the diet and very few people can sustain zero carbs

5. fasting to help with IR? Jason Fung's protocol.

Jeff: he is in favour esp with a plateau. He doesnt mind a few nuts, broth, bit of fat (mct in coffee). he thinks eating once a day eating is optimal. He isn't in favour of extended fasts - rather prefers the concept of skipping a meal.

Miriam: likes a stepwise aporoach. She supports first keto then fasting only once ketoadapted.

Antonio: needs cycles of IF to keep his diabetes in remission. He thinks its critical in recovery from T2DM

Georgia Ede: struggles with fasting. Dairy and protein spike her glucose levels.

Andreas thinks fasting is great and has synergy with the ketogenic diet.

Ivor thinks fasting is a power tool for meetings!! Better, sharper!
But seriously, its a powerful tool for resolving metabolic issues

6. Delegate thanked the speakers for generously sharing their knowledge

7. exercise: ultramarathons - what is the upper limit for exercise? knowing oxidative stress is mitigated by ketones? is the upper limit higher? Is there is thing as too much exercise?

Jeff: it all depends - it's individual. Mark Cucuzella. He does believe there is a thing as too much exercise.

Peter: there is more to health than nutrition and exercise and its possible to take things to excess.

Jackie : tried to train for a marathon. Overtrained at 6 days a week whereas 5 days was ok. Found she had a threshold at which she felt well. Feels its very individual.

Ivor: Volek is the expert. But he has noticed in colleagues that they have better recovery. He believes it is safer to do ultramarathons in ketosis.

8. Women and aging and keto?

Miriam: doesn't feel women who do well on a 4 hr eating window - she feels they do better on 6hr or 8hr eating window and it gets harder with age. She suggests one goes with how one is feeling.
She feels there should be a 4 hr gap between dinner and sleep.

9. probiotics:
there are no RCTs.... its all observational.... what to do?
studies are in rats and they are vegetarian...

Andreas: feels microbiome thing is hype atm based on weak evidence but he could be wrong

Ivor: too soon to know what is the right microbiome mix

Georgia: in psychiatry the science is in its infancy and there is no information to recommend probiotics

10. should we be supplementing omega3s?

Miriam: should aim to get enough from fatty fish and the ratio is more important

Ivor: new study - comparing mice with different 3:6 ratios.
high % of 6s in mice is obesogenic

polys are for cellular structure and cell signalling, not for fuel

Antonio: he makes sure he eats sardines regularlyàq and takes omega 3s daily. 3grams of omega 3s daily in the triglyceride form.

Georgia: omega 3s and brain health. Prof Crawford. She wonders how much omega3 we would need if we werent eating omega 6?
DHA: required to create synapses. Crucial when pregnant and breastfeeding

Miriam: DHA gets across the BBB with one special unique transport protein.

11. What to tell friends and colleagues?

Georgia: ask them what the science is behind their beliefs.

12. Nutritional ketosis in a hospital situation - is there any problem with this in a sick, septic, acidotic patient?

Miriam: ask family to bring the food and be quiet about it. Eat the protein that the hospital serves, request extra butter, and get family to bring in more butter.

Antonio: its impossible to expect the hospital to give this food because of the dietary guidelines.

Jeff: Mark Cucuzellas hospital does offer low carb options.

Andreas: might be hard to start a sick person on a low carb diet

13. Wants more women's activism. Why are women not doing more research or more prominent as subjects of research

Jeff: there are women who are metabolically ok but have a lot of subcutaneous fat.

Peter: are we expecting too much from the science in terms of individualisation?

Georgia: women are more sensitive to the hormonal mileu (because we get pregnant and have to listen to baby and placental signals).
but it wouldnt make sense evolutionary-wise for men and women to need different diets

14. most common novice mistake new keto people make?

Antonio: be patient with yourself , it will take time
Georgia: perfectionism, setting up for failure, female aversion to being fat
Ivor: understand underlying mechanisms
Jeff: eating too much
Jackie: learn about how it works
Miriam: failure to recognise stress
Andreas: too little fat and salt
Peter: dont be evangelistic rather model it

15. Comments on total protein and feast and famine?

Jeff: protein intake is individual. Start with 1gm/kg. He does consider longevity and MTor

Ivor thinks the protein activating MTor is hyped. IgF1 study - he isnt convinced. He's not sure about the evidence.


ANN HATHAWAY

link to video: https://www.youtube.com/watch?v=wAmPO6lde4o&t=256s
link to slides:
Apoe 4 group Bioidentical Hormones and Cognition 8 5 17.pptx


bio-identical hormones, cognition and AD

Her passion for 20 years is the brain and oestradiol.

most important to consider in
*apoe4
*family history AD
*history major depression
*women with cognitive decline under 65yrs

evidence for benefit?
1. brain has receptors for 17 beta estradiol (E2). E2 improves cognition.
2. if true - why not generally utilised? poor understanding and fear of breast cancer

* basic science is unequivocal
* observational studies are problematic because they mixed in premarin and provera and different modes of delivery and muddied the data.
* wharton w et al. 2009 potential role of pathophysiology and prevention of AD. Am J Trans Res


*E2 receptors associated with maintenance and protection of multiple brain structures.
*E2 receptors high density in hippocampus; amygdala
*E2 increases density and plasticity of hippocampal neurons


E2 and mitochondria

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E2 and neuroprotection and neuromodulation

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Vascular benefits of E2
E2 slows oxidation of LDL


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E2 and beta amyloid

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APP cleavage pathway and E2

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So if the evidence is clear, why is this therapy not utilised?

WHI study set bioidentical HRT research way back.
The cognitive sub studies showed increased risk in over 65 women started on prempro for the first time.

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why so negative?

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Here is a study with women who had started HRT near the menopause Image


other studies

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its hard to get studies in HRT now after the WHI, but there are a few good quality studies

53 women:
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same 53 women: half on, half off
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Same group of women as the telomere study:

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another study double blind crossover trial in AD
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BHRT BASICS

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Anne uses HRT only on the skin. Buccal may be swallowed.

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projector died....so no slides for now...

She only uses gels or patches. Creams from compounding pharmacies give greater flexibility in dosing.

Estriol is a weak oestrogen but is very effective for atrophic vaginitis. Only available from compounding pharmacies.

She does use testosterone, not for everyone. She uses it for libido and muscle mass.

Issues:
still having hot flashes: alcohol blocks processing of estrogen (shares the same clearance enzyme) and then the processing enzymes have been upregulates and then once the alcohol is gone, the oestrogen level plummets.
Also other meds can interfer with elimination and levels


Anne uses estradiol and a little of estriol. no estrone.

Progesterone for uterine protection:

18 to 24 days on. Increases P4 receptor sensitivity. But if women sleep better, Anne uses it every day.
Remember progesterone can go down a different pathway and increases cortisol and they dont sleep

15% of women become very sedated on oral P4. Scandinavia - vaginal P4 doesnt cause sedation in many of these. Its metabolized via different pathways.

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Suggested minimum P4 levels for a given E2 level:
We want E4 generally around 40 to 80 (no literature helping define the best level for the brain)
But younger women in their 40s with early menopause one needs 100- 120.

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many options for obtaining good progesterone

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Anne has many patients who chose to take P4 even without a uterus

BREAST CANCER

only two RCTs are the Keeps study 2014 and the estrogen alone arm of the WHI.

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Observational study:

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Prevention breast cancer:

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Prefer ultrasound to mammograms.
She is more comfortable with 2 yearly mammograms. She has had a couple patients whose breast cancers were missed by thermography so she has lost faith in it.


Below see metabolites and breast cancer risk......see photo below for reference.....


We want to make methylated 2 methoxy E2 via activation of CYP1A1.... we want to enhance this pathway - cruciferous veggies and iodine enhance this. COMT is enhanced by B12 and methyfolate. We do do not want to make 3,4 quinone which can enter the nucleus and break DNA. CYP1B1 is promoted by xenoestrogens. Even if we do make 4OHE2 we can move it to neutralized version 4 methyoxy E2 by upregulating methylation.
CYP3A4 upregulators (eg medication ) will drive the pathway towards estradiol.

but we can neutralise 3,4 quinone with increased glutathione ie NAC and alpha lipoic acid

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13C DIM and breast cancer

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questions:
1. is oral glutathione absorbed? liposomal might be better delivered to the cells
2. thin women have high SHBG. A high SHBG results in less free estradiol to be active.
3. "normal ranges" are not always applicable
4. no data to support her stated optimal BMI range 18 to 22. Its her personal opinion.

Then we had a lovely dinner under the stars and moon with Anne. Lots of lively discussion.

Tomorrow we are off to the Zoo for some well deserved R&R.
My brain is full....its been fabulous.
The videos of our pre-dinner talks will be available later. George needs to edit and link them.

Please feel free to ask questions or comment.
Its a LOT of information!
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Julie G
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Re: Stavia's report on our meetup in San Diego 2017

Postby Julie G » Thu Aug 10, 2017 6:58 am

Check out brother Dave Feldman's latest blog post. He's graciously complimentary of our group. He delivered an excellent talk that will soon to available to all via video link.

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Stavia
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Re: RE: Re: Stavia's report on our meetup in San Diego 2017

Postby Stavia » Thu Aug 10, 2017 8:26 am

Juliegee wrote:Check out brother Dave Feldman's latest blog post. He's graciously complimentary of our group. He delivered an excellent talk that will soon to available to all via video link.
what a sweet man.
I love being called "wickedly smart"
I think we need a Tshirt.
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KatieS
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Re: Stavia's report on our meetup in San Diego 2017

Postby KatieS » Thu Aug 10, 2017 8:38 am

Stavia, thanks for all the work to post these slides & notes---much to review & digest. Sorry to miss this meet-up as I'm overwhelmed on the home front. Your new photo is the same hairdo as your childhood pic-cute!


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