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.
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
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.
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
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
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.
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.
Coronary calcium score
The calcium is not a risk factor - it is actually the disease.
Coronary calcium score versus Framingham
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.
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.
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
Diagnosed: ast alt ggt, u/s, fibroscan, CT, etc - all not very sensitive.
He uses a risk calculator:
The old textbooks say diabetes -> NAFLD but in fact it's the other way around!!
pathways to NAFLD:
(point 2: more than 60gms fructose or sucrose)
exercise and NAFLD
we need exercise to use glycogen stores, excess glucose - de novo lipogenesis - stored in liver
after a few days of inactivity our muscles become insulin resistant.
a pathological rise in insulin activates transcription factors that turn carbs into fat
(de novo lipogenesis)
confirmed by Berkley study
NI =normal insulin
independent of obesity
It is now established that de novo lipogenesis is a distinct characteristic of IR.
there are dysfunctional adipocytes in NAFLD.
dysfunctional IR they get inflammed and can't expand and excrete inflammatory cytokines then ectopic fat (no longer only subcuraneous) occurs.
IR is independent of obesity
black spots on the right are macrophages
right hand side says: lipid overflow - ectopic fat
its probably the lipid overflow that is the problem: its the fat in the organs
ectopic fat and CVD risk
its the ectopic fat thats the problem
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:
this guy has the highest mortality:
Metabolically healthy people store their fat subcutaneous. Like even sumo wrestlers who do heaps of exercise.
fatty liver is both a sensor and cause of IR
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.
when the pancreas gets fatty, the alpha and beta cells become insulin resistant.
Therapy for NAFLD
only lifestyle modification
most of the liver fat is from dysfunctional adipocytes (the 59% in the slide)
exercise - multiple pathways
Newcastle study : reversal of diabetes
as the liver fat reduced, so did the hepatic glucose production and the fasting glucose
as the pancreatic fat reduced, the insulin production recovered
obesity is not an accurate marker. It is the ectopic fat that matters. everyone has a personal fat threshold
keto in NAFLD
been a few small studies.
hepatic TG reduction was greater in the keto diet altho same weight loss
2 days and 2 weeks
then he ran out of time ***** and went to his last slide:.
**** I am photographing the next slides from my computer a week later:
****** 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
******I added this section a week later once I had access to the slides
The secret of the ruminant- we've all been fed a lot of bull
grass fed vs conventional beef doesnt make an appreciable difference to omega3s
how much salmon would you have to eat to balance omega6s in vegetable oil.
(soy is really bad!)
what about hormones in non grass fed beef?
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?
avenues of political action
how do we get the message out?
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.
PANEL : QUESTION AND ANSWER SESSION
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.
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.
link to video: https://www.youtube.com/watch?v=wAmPO6lde4o&t=256s
link to slides:
bio-identical hormones, cognition and AD
Her passion for 20 years is the brain and oestradiol.
most important to consider in
*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
E2 and neuroprotection and neuromodulation
Vascular benefits of E2
E2 slows oxidation of LDL
E2 and beta amyloid
APP cleavage pathway and E2
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.
why so negative?
Here is a study with women who had started HRT near the menopause
its hard to get studies in HRT now after the WHI, but there are a few good quality studies
same 53 women: half on, half off
Same group of women as the telomere study:
another study double blind crossover trial in AD
Anne uses HRT only on the skin. Buccal may be swallowed.
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.
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.
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.
many options for obtaining good progesterone
Anne has many patients who chose to take P4 even without a uterus
only two RCTs are the Keeps study 2014 and the estrogen alone arm of the WHI.
Prevention breast cancer:
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
13C DIM and breast cancer
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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