I would like to know if this works with iced green tea as well. I used a method of one meal per day to loose 50+ pounds. I found it pretty easy, all in all, but have regained about 20 now and need to get back on it. I think I will give iced green tea a try! (I'm not crazy about hot green tea, but like it fine iced)

I use tea as a method of extending eating intervals.  It works well.  I'm sure a lot of it has to do with the "upper" effect.  Ie.  uppers reduce appetite as a result of blocked sensory.

I find fasting and sensory blocking to be counter-productive.

May be other effects but caffeine and it's cousin theobromine in the tea are pretty reliable appetite suppressants.  But isn't getting jacked up (even if only a little) a bit counter productive to some of the potential benefits of fasting?  The idea is to rest your physiology while catabolism is in full swing. Activating the sympathetic nervous system so you don't have to experience the sensations you don't like during the early stages of fasting does not seem to me to really promote that.

Yes, green tea reduces my hunger; I just use Tetley in the bag. Some of the greens do not have a satiating effect on me, nor do any of the black teas. Coffee increases hunger for me. Bullion cubes or OXO packets also help. I make a 1.5 l thermos, and suck on that until its done. Some days 3 or 4 of them in a day. I think I have more hunger than most people, but I am down 55 kgs, 2 to 4 years ago and have been down for 2 years.

The other thing that helps me is chew-able Vitamin C, a couple of 500s any time I feel hungry. It seems to raise BG, possible due to BG sparing, as it is required for far oxidation, or inside cell far transport, depending on who is explaining. Two 500's raise my BG form 4.0 to 5.3 -- OK US 72 to 95.
I am off wheat mostly; occasionally Clam chowder, sausages, and a few crackers for low BG issues. One cracker raises BG 1.5 at 15 mins.

Thanks for the one hour BG idea. Some of my higher protein meals were a problem, like 280 Calories of canned salmon ran my BG to 9.0 (OK 162). And my doctor says I an not diabetic but my a.m. BG sure is erratic, 4.0 to 6.2 this week.

My experience is similar.

Chris

Hey Phyllis, I'm with you. I have been drinking 4 cups green tea made with tea bags and then chilled and have noticed that I'm not as hungry but didn't really connect it with the tea itself. I need to lose 50 lbs and I like the idea of one meal a day.

Green tea, or any tea actually, makes me a little ill on an empty stomach.  Not sure but believe it is the tannins.  I also was consuming a lot of green/white tea while fasting and I just felt really acidic and my face got red splotches, which seems to coincide with acidity.  I know the net result is supposed to be alkaline for green/white tea but that has not been my experience.  Recently, I've been adding a tablespoon of apple cider vinager to a cup of warm water.  Went a fairly easy 18 hours today but did break down and had four or five macadamia nuts around 12 hours in.

I absolutely drink green and lightly oxidized oolongs during my fasts.   It curbs the hunger and provides focus.  Been doing it for 2.5 years.

After millennia of human starvation, to think that we still have tons to learn about fasting used for health purposes!

Phyllis--While I've not tried it personally, nor do I know of any formal data, I expect that iced green tea--provided it is real brewed green tea, and not the bottled variety--should work every bit as well.

I am unable to drink green tea at all on an empty stomach, I will absolutely throw up if I do.  I end up with pullovertothesideoftheroadI'mgoingtopukeyesseriously!".   I actually threw up all over my suit once which was really special.  Green tea with food often makes me queasy as well.  I am allergic to oak so I think there may be a tannin connection as some heavy oak wines are problematic for me.

I am making today a fast day. I have been drinking a mix of green and white tea but it is decaffeinated.  How often should one fast?

For those who get dizzy on green tea, try puerh tea.  It is a fermented green tea that is also much lower in caffeine and it taste much better than green.  It is the equivalent of drinking an aged red wine over 2 buck chuck.

This question has been around for quite some time,  but no one seems to know the answer for certain.

Theoretically at least, consuming antioxidants during fasting could be detrimental to autophagy (removing "junk" cells), since antioxidants might suppress the stress response from fasting. This is why some studies show antioxidants and exercise are a bad combination -- you *want* some stress to happen so that the body can adapt to it.

Then again, there is the theory that small amounts of antioxidants actually work through the same mechanism as fasting and exercise -- hormesis. In which case fasting + antioxidants might complement each other. But that's just speculation.

What we do know from studies is that green tea seems to increase weight loss, for example when combined with calorie restriction (and thus should apply to fasting):

http://inhumanexperiment.blogspot.com/2009/04/green-tea-increases-weight-loss-during.html

And when combined with exercise:

http://inhumanexperiment.blogspot.com/2009/03/green-tea-extract-increases-insulin.html
http://inhumanexperiment.blogspot.com/2009/02/green-tea-extract-enhances-abdominal.html

And when combined with capsaicin (from chilli pepper), it reduces the feeling of hunger and thus calorie intake:

http://inhumanexperiment.blogspot.com/2009/04/green-tea-and-capsaicin-reduce-hunger.html

So all in all, whatever the mechanism is, if you're fasting just for the sake of losing weight, I'd say green tea is a pretty good bet.

- JLL

Would depend on the length of fasts, but the East Stop East method advocates two fasts per week.  My fasts are now usually shorter, as they kind of trained me to stop grazing. I usually don't bother with breakfast now. The more you eat, the more you want to eat sometimes.

I'm subscribed to your blog, but since  you changed format the posts haven't been showing up in my mail box.  I tried to re-subscribe, but am told I'm already subscribed.  How do I get back in the loop?

Nina

Anyone not receiving email versions of this blog:

I wonder if the shift over to the new platform caused a few glitches. My blog IT help is out of commission temporarily. Therefore, please sign up again at the top.

Sorry about that.

Yes, I completely agree with you! I went 90% wheat and sugar free from November 2010 to February 2011 and lost a whopping 2 pounds. It wasn't until I went to 95% or more wheat free that I was able to start losing weight. I am now 100% wheat free and I have lost 36.2 pounds in 15 weeks. I have also been able to significantly cut my caloric intake to 500-700 calories per day (sometimes less than 500) using iced jasmine green tea. I truly believe that a diet that is lower in calories is better for health. I typically drink 6-8 glasses a day and I really enjoy it. It helps immensely with any hunger I may have and completely satisfies my sense to eat. I use any of the varieties available in tea bag (Numi, Two Leaves and a Bud, Stash, and Mighty Leaf are my favorites). I typically choose whatever's on sale. I also drink a full glass every morning prior to eating and that also seems to stimulate my colon which is a bonus as well when consuming such low caloric counts.

On a cholesterol and BG level, my family genetics are something that should be studied. While I started my diet at 234.8# on 2/15/2011 (I'm 5'3" and 47 y/o female) my total cholesterol was 167 and my HDL was 54. My 102 y/o grandmother however, has a total cholesterol of 155 and an HDL of 115! My 76 y/o mother also has the same great results but her HDL is "only" 109. Neither of them are on any medication for cholesterol and both of them eat a diet fully based on things we berate on this blog (cookies, bread, ice cream, fried foods, etc). Neither are overweight either. I'm eager to see what my levels become when I reach my goal weight. Maybe I can surpass that HDL of 115!

I tried that before I posted and it tells me I'm already subscribed.

Nina

About 15 years ago I went on a fast and had only water.  The fast lasted for 10 days.  No green tea.  Just water.  After 18 hours, I completely lost any hunger.  Meanwhile I continued to cook meals for my family.  I also continued to go to work every day.

The experience seemed wonderful.  I had been suffering badly from asthma, and all symptoms disappeared!  I could have kept going forever without eating.  However, after 10 days I started to have problems with urination.  I began excreting small, hard pellets.

I went to the doctor, and he exploded.  "You bloody fool!" he said.  I had altered the ketone content of my blood.

So I started eating again.  My first meal was brown rice (no salt).  It was the most beautiful meal I ever had.  Gradually I returned to normal eating.  Gradually I returned to my asthma symptoms. Gradually all meals started tasting the same.

Did I lose weight?  I'm not sure, as my ketone problem overshadowed all else.  Did I need green tea or anything else to curb my appetite?  No, plain water (not even distilled or bottled water, but tap water) was good enough. Do I recommend fasting?  In moderation.  10 days is far too long.

Is the fluoride content of any tea (Camellia sinensis) not an issue?  Data on ppm fluoride vary but they all appear to be quite high and much higher than water fluoridation levels.

Try Jasmine Tea which is green tea with Jasmine flowers.  Much tastier.
I don't like plain green tea myself, but I love Jasmine tea.

There is only one problem with green tea: Pesticides.
Most green tea is imported from India or China because it is the cheapest. On testing, a serious amount of pesticides, fungicides, microcides is found regularly. I wonder if this diminishes the health aspect of green tea.
I used to buy organic green tea from Japan but after Fukushima that option is also out.
Still, certified organic is the only option left, I suppose.
Renfrew

Just tried again and I get the same message 'You're already subscribed'.  Pity that Feedburner no longer delivers to me.

Nina

Started IF HFLC diet three months ago. 30 lbs lost and A1c down to
5.1 !! (was 6.7 ) . Curiously I have been drinking green tea during the daily 18 hour fasts and hunger is a rare occurance,  hunger pains last only a few seconds. The tea helps,  body and mind trained to not think about food until
nightly free for all. Thank you, Dr. Davis and contributors>

2 Gabriella

Flouride IS an issue with green tea. There are known cases of flourde poisoning with excessive green tea drinking - woman drinking equivalent of 20-30 green tea cups per day. This isn't something to worry about on regular usage but if you do it on IF with reduced nutrient input and more frequently to reduce appetite it can become a problem.

White tea has lower content of fluoride as it is harvested when plant is still young. It is much more expensive but overall better then green tea due to less processing and lower fluoride content.

Coffee works for me absolutely amazing in reducing hunger. To some people, however, it works the opposite way. My friend develops hand tremor, nervousness, and heat. The same thing she got from the green tea but not other teas. Caffeine might be problematic for some I guess, or maybe tannin. We are currently in the process of isolation of such substance.

To reduce appetite, I found the following valuable:
- Garlic, fresh, in tomato juice (parsley can be included to block the smell). The capsule doesn't work.
- High intensity exercise, short bursts of 15-20 minutes will shut down digestive engine and you will not be able to eat for hour at least.
- Marijuana restriction - its usage during fat loss might be problematic due to activation of CB1/anandamide system.
- Periodic IF can learn body to handle prolonged food abstinence. I find that 16-24 hours fast is enough.
- Almonds, 10-15g, are cool, especially if you tend to go crazy before sleep - its mostly fat which doesn't rise insulin during night. 2g CHO, 3.5g MUFA, 1g PUFA, 2g P is enough to make your hunger go down at least a bit and still keep your insulin down.
- Water

I would suggest extensive supplementation during IF - especially Vit C (at least 2g as frequent as possible), Mg, Iodine, Selenium, Idebenon.

Drs. Davis or Taylor (or anyone else) have you noticed any issues with accumulated caffeine intake from multiple cups of Green Tea throughout the day?

Dr. Davis, I hadn't heard about the dangers of pesticide use relating to green tea (as mentioned by Renfew, above)...is this a viable concern?  Since green tea is loaded with antioxidants, do the benefits outweigh the risks in this case?

I have been drinking about two to three cups of Tazo Zen Green Tea for quite awhile now (hot, as well as chilled), and enjoy it very much.  It does seem to curb cravings quite well.  I also notice increased energy without the edgy side effects that coffee sometimes causes.  Before Tazo, I was not a big fan of the taste of green tea, but the Zen blend also contains lemon verbena, spearmint leaves and lemongrass, which enhances the flavor and makes it quite delicious--providing an "aromatherapy experience" along with the tea consumption.  

Thank you for your informative comment JLL!

me too!i keep hearing about green tea for fasting, so i took it on day 2 i think and was detoxing to fast cos i took it on a empty stomach....:/

I drink the Tazo Zen Green Tea from Starbucks. I prefer this green tea over any others, however I have noticed extreme dizziness when I drink this tea. Has anyone experienced this? I even bought the tea bags to brew at home, I do not add any sweetener and love the taste. I occasionally drink black tea or soda and do not get the same dizzy feeling, therefore I believe it is not caffeine causing me to feel dizzy it's just green tea. Any suggestions or comments? I like the benefits of green tea but not sure it's worth the dizziness.

Wacky. No, I'm not sure why this happens.

Perhaps its some mixture or proportion of the theaflavins or other components. There are hundreds of green tea preparations available. It might be worth finding a happy alternative.

I have been using green tea for years in weight loss.  You are right, it is not a "speedy" remedy and you will only recognize small affects it has, however, it does work.  On average, it is said that you can burn anywhere from 70 to 80 calories a day drinking green tea.  This is assuming you are drinking at least 3 to 4 cups daily.  It should be combined with water and a healthy diet and exercise.

About the dizziness, I had severe vertigo in the middle of the night, i.e. at 3 am (my blood pressure was 130/100 pr 90), and the day and the night before sleeping, I consumed 4 mugs of green tea. The vertigo was associated with vomiting (which relieved the vertigo for a while). The vertigo lasted till the next day (vomited 4x). The green tea was a gift from a friend who came back from China-loose dried leaves. After that episode, I think I can't make myself to drink green tea again.

I sometimes do a morning 'flush' of green tea, up to 4 freshly brewed mugfuls, with the addition of a squeeze of fresh lemon, which complements the taste and gives extra benefits, vitamin c and supporting detoxification.

I recently saw a BBC documentary which demonstrated an optimal brew time of 7 minutes for maximum anti-oxidant release.

Also, the cooled teabags are an excellent beauty treatment for the eye area, squeeze excess moisture and relax for a few minutes.

Am reluctant to extend beyond midday due to stimulating effect of caffeine, how about switching to other teas that deliver other useful benefits? Ginger, fennel, liquorice come to mind.

Blessings of health

What does one eat if they are wheat free, low carb, and low saturated fat? Can anyone give a sample day for this plan?

Have you tried T4/T3 adjustments with apo E4?

How can one find out if one has Apo E4?

Is it possible to have the same reactions to fats such as large increase in LDL, mostly large with little small LDL?  At one point i was 100% small LDL; restrcting carbs and increasing fats of all kind(good ones only) my NMR was 2098 LDL of which 200 were small were small.  HDL was 69 and TRGs 62.  Only way to get these numbers down is to be on statin and zetia.  Thought i was an ApoE 4, but test showed i am ApoE 3/3.
Perhaps i am a hyper-absorber of fats- maybe as bad as ApoE4?   With statin and zetia i can reduce the numbers to LDL total of 640 and <90 small.    So maybe the high fat diet is not so great even for those who are not ApoE4.
Thanks for your thoughts.

I'm getting my ApoE status tested soon.  I've been quite liberal with the healthy fats (olive, avocado, pastured eggs) and include saturated coconut oil and dark chocolate.  I also have high LDL particles - about 1500, but only 139 are small without statins.  I would love to find out I am 3/3 because I've already restricted grains and a variety of foods that I tested as allergic too including nuts.  I asked Dr. D on the forum if having <10% small particles was good news, but he was still worried about the total LDL.  I guess we will see how worried I should really be shortly.  BTW, I've got high Lp(a) at 26mg/dl, so I really don't need another strike against me in my plaque battle.

Lost a nice technical ApoE explanation  I spent a lot of my time on to "server error" .
I'll just lurk from now on.

Mighto:
Please stay here and enlighten us with your comments. Glitches can happen. I made it a habit a long time ago to just copy my text (Ctrl.A, Ctrl. C, on WINDOWS) before sending it. It is easy and takes no time. Text is preserved and you can try again.
I for one am enjoying your musings tremendously.
Cheers, Renfrew

What Renfrew said. I've run into this problem on blogger regularly where it decides to log me off while posting a comment. Now I always save any longish comment before posting. Better safe?

Digging into my 23andMe data, it reports back on APOE e4 status

You can find this as part of the https://www.23andme.com/you/journal/alzheimers/overview , or just check the rs7412 & rs429358 SNP's directly.

I am an APOE 3,4, and here’s what I eat on week days.
Breakfast.
Steamed raw vegetables (eggplant, zucchini, bell peppers, mushrooms, Mexican or yellow squash). Add yellow mustard and dry spices.
Natto twice a week (1 box Mito natto, throw away their soy sauce and mustard packages).
Frozen blueberries (1/8 cup), 3 tbsp flaxseed meal, 1 cup unsweetened almond milk - all microwaved for 2 min. Add ground cinnamon.
Half-ounce piece of part skim milk mozzarella cheese.
Coffee.
Lunch.
Frozen vegetables (California blend – cauliflower, broccoli, carrots) microwaved (reheat). Add a boiled egg, 1/4 avocado, yellow mustard.
Dinner.
Cooked or baked vegetables (cauliflower, bok choy, green cabbage, rapini).  
Sautéed or baked fish (tilapia, salmon, perch, trout), chicken breast, or ground turkey meat balls. Add yellow mustard, horseradish, and dry spices.
Generous amount of raw vegetables (green lettuce, pickles, tomatoes, bell peppers) with hummus.
Decaf tea with a 1/10 serving piece of 90% dark chocolate, half-ounce mozzarella cheese, and some almonds or sunflower seeds.

My daily fruit serving includes a cup of frozen dark berries (blueberries, raspberries, blackberries) from the Costco Three Berry bag.

back incollege i did a report on cancer and ottowarburg and i remember this gene being incredibly linked to cancer risk....any truth to that?

Hi, Steve--
There are indeed genetic predispositions outside of apo E4 that can provide for this response, e.g., apo B receptor variants. What is not known is when you've crossed a threshold of mostly or purely large LDL that is undesirable. Despite $2 billion spent on statin drug-related research, we still have no answer on this question.

Hi, Buck--
Similar issue as the question posed above by Steve: We just don't know what an "allowable" quantity of mostly or purely large LDL particles are. For a working value, I've been trying to keep NMR-derived LDL particle number 1500 nmol/L or less when LDL is purely large, but I have no endpoint data to justify this.

Great program, Gene, given your pattern. And I am impressed at your courage to eat natto!

Hi, Mallary--

Hardly my area, but I believe that the relationship between apo E4 and cancer in various sites is complex and modulated somewhat differently than in other apo E genotypes. Some discussion:
http://aje.oxfordjournals.org/content/170/11/1415.long

Hi, Simon--

The full diet is articulated in detail, including scientific rationale, in several reports on the Track Your Plaque website; link above. Chapter 9 of the New Track Your Plaque Guide is also devoted to this.

As you see, I will be putting out recipes here and on the Track Your Plaque website in coming months.

even 1 reconstructed paragraph just  lost to "server error"

ApoE joins with ApoB and is carried in VLDL and chylomicrons; it is ApoE that binds to tissue cell LDL receptors to start normal uptake. Inside the ApoB with lipids breaks off and heads into tissue cell lysosome.
Meanwhile ApoE and the LDL receptor head back to that cell's membrane, with ApoE carrying some cholesterol out of that cell to build into an HDL molecule for recycling.

I have the worst of both worlds, I think, as I am E2/E4.  Dr. Davis, do you have a specific program for patients with this genotype?

So, Gene, I'm curious.  It looks like you have an extremely low intake of protein.  How are your labs and what kind of activity do you do during the day?

Eggs, natto, fish, poultry, and nuts are all rich in proteins, correct? I increase my portions of fish and poultry when I go to gym. I also add canned fish on these days like tuna in water or sardines in mustard sauce. I used to consume large amounts of tofu, but stopped recently based on some negative information I learned from a TYP member forum.
Every weekday I typically walk to and from the train station, 25 min each way. I work out two or three days a week following the slow burn routine; I do cardiovascular, too. I also ride my bike for 2 hrs every weekend.
I am a software engineer, so I spend most of my business hours in front of a computer.
Before I learned about my APOE 4, I used lots of olive and canola oil and was a vegetarian, but had already reduced carbs. My labs were pretty bad and actually much worse than when I ate lots of bread and oatmeal every day. In mid-December 2010, I started eating as described above plus taking niacin (500 mg) and Crestor (10mg). I was already taking the standard TYP supplements – vitamin D3, fish oil, iodine. At the end of March 2011, my NMR was the best I had ever had: LDL-P 568, LDL-C 70, HDL-C 55, Trig 24, HDL-P 29.5, Small LDL-P 293, LDL size 20.4, HDL size 9.7, Large VLDL-P 0.7, insulin resistance 16. I don’t have genetic lp(a). I know the results can be better, so I am looking forward to my next NMR due in the fall.

I'm confused. When you say 1 in 4 have this gene are you saying it's a *problem* in 25% of everyone? As in one-quarter of us should be eating like Gene K (above)? Or is a case where the gene isn't always active or something?

I recently wrote about Alzheimer's on my blog and this question came up in the comment section.  I think about APoE4 completely differently than you do and here is why.  APoE4 confered humans the ability to migrate out of the sahara and north and south to live in climates with less solar radiation.  It allowed us to live with lower vitamin D levels.  Moreover, its presence alone means nothing unless it is accompanied with the epigenetic triggers that make it dangerous.  Dr Davis you and I both know the disease you treat (heart disease) and the one I treat (Cerebrovascular disease) are the same disease just found in different organs.  SO i think we have a lot in common in what we do but how we think about thi sissue is different.  Here is my take.  I posted this answer on another forum and I think it needs to be discussed here.

I think the ApoE4 story is an interesting one and one I briefly touched upon in my AD blog.......I will revisit it.......but ultimately I dont think it is that important if you live an optimal life from 20-60. ApoE4 means much if you make poor epigenetic choices. I think people who come here do do what the rest of America does.

The other reason I think it means little is the epidemiology of ApoE4 in those over 80 yrs old. It does not have any major impact on healthy aging once you get to old age. That tells me that the epigenetic signals need also be present for it to matter.

ApoE4 is like dynamite.......and high insulin and high PUFA consumption and lowered total brain cholesterol (due to altered lipid uptake) are the major lit matches. If they exist by themselves they are harmless......but if they are brought together you are going to get heart disease and AD early and get taken out.

Dr Kruse

So everyone who is eating or planning to eat a high fat diet should get tested for E4, or are there some things that indicate it's probably unnecessary?

Dr Kruse -

It's pretty scary for me to think that maybe I am not supposed to be eating very much saturated fat. If it's true that is unbelievably lame. This is why I'm thinking I need to check to see if I am ApoE4. (How do I test for that?) If I am, then it may explain why, even on a Paleo diet, my LDL is mostly small dense. Are you suggesting that if I keep PUFA very low, like cut out my only remaining source (almonds/pecans), that this could be a key to producing more pattern A LDL? (By the way... I have chosen to eliminate all nuts and nut butters, regardless).

-Jack Kronk

Thanks so much for the thoughts - I am an E4/E4 eating a Paleo 2.0 diet.  As I understand it, high-protein is not a healthy diet, so low-fat & low-carb is not a good idea.  Fat is the healthiest macronutrient, so I'd love your opinion on which types of fat are best for E4s.

It sounds like you have concerns about saturated fat, and of course I avoid n-6 PUFAs and get lots of n-3s from grass-fed animals & fish oil.  What about coconut oil?  Olive oil?

What sort of HDL/LDL/etc  numbers would you look for in an E4/E4 as warning signs?  As health signs?

BTW, I blog occasionally on APOE4 at primale4.wordpress.com, am going to quote your post there.

Thanks for that, Gene.  I may need to go your route with my profile.  I'm following TYP pretty religiously and am having my 6-mo labs this month, so hopefully they will be improved from last time.

Jack as I mentioned to you on my blog I think you clearly need context.  I think your epigentics are telling you something.  But here is what I cant tell you and neither can anyone else.......without testing!  You need to be tested to get that context.  I think your diet you posted gave many clues......but even I did not jump to the easy conclusion.  I think your real underlying issue is multifactorial but your VAP strongly points to a leaky gut as a source of the sdLDL.  I think the bananas and cream are problems too.  Your O6/O3 ratio maybe bad and yes......you may have a bad set of allele's for ApoE4......but guess what!  Your HS CRP was very very low.  This tells me that your match is not lit.  So you may only be carrying a stick of dynamite.  Again......carrying dynamite is not going to blow you up.  This is why you need testing to get more context.

We send our ApoE4 patients to an nearby academic lab for testing.  One is likely available in your community because cardiologist and neurologist are ordering this test quite often now.  I think your PUFA content of your diet and of your tissues is critical.  In fact for AD the PUFA content is a major factor.  I believe it is a huge factor for CAD disease as well.  Wheat, Carbs, and PUFA's all drive sdLDL production.  Its not just one part of the diet that does it.  Moreover, the more leaky the gut the more sdLDL one will have as I laid out in my VAP blog that I dedicated to yourself.  I think your case is quite representative to many thousands of people and I am glad we are talking about it here because Dr Davis is a cardiologist and is coming at this issue from a different angle than I am.  I think however when the story plays out.......we will be in the same neighborhood because human biochemistry pathways are constant.  The fuels and hormone status and the situations in our guts are the covariables that make this issue more confusing.  I think people need to know why Apoe4 is important.  It conferred an adaptive advantage to move away from the equator to lower solar radiation and lower vitamin D levels.  This adaptation is seen in many american african americans.  The other interesting finding is that the liver of these patients makes more cholesterol to try to raise the D level and pregnenolone level to offset the deficit.  It never does.  But when this set of circumstance is mixed with a high carb low fat SAD (PUFA rich) it destroys the heart, vessels and brain.  This is what we see today in many parts of the world.  Their diet is now completely mismatched for the original adaptation.  I think if you tweek the diet when you know the epigenetic variables you can easily over come an Apoe4 positive test if youre willing to change.   But you need to test!

Hi, Tim--
Very rare, as you likely know.
I believe that you simply deal with this on a practical level, i.e., deal with the small LDL and insulin resistance issues and postprandial abnormalities from apo E2 as you ordinarily would. Then deal with the LDL-accumulating aftermath from the apo E4 component.

Thanks for the insightful thoughts, Dr. Kruse.
I'm not sure how your approach folds into mine, though fascinating. I do agree that apo E4 is made much worse by the means you cite, i.e., polyunsaturates, carbohydrates that trigger small LDL. This is why, despite the LDL-accumulating effect of apo E4, I focus first on reducing the small LDL component, in effect an anti-inflammatory, glycation-reducing, oxidating-reducing approach, followed only then by dealing with any large LDL-increasing aftermath.
What is not clear to  me is how atherogenic the large LDL is at higher levels in the setting of apo E4. As you know, one of the greatest concerns in apo E4 is that its effects may not be confined to lipid effects, but may extend into non-lipid effects. But that is such poorly charted territory.

Hi, Patri--
The formal data on the various fat fractions and apo E4 are, unfortunately, very skimpy.
Saturated fat clearly increases whatever LDL dominant form there is. However, other forms of fat, even omega-3 fatty acids, also increase apo E4. This become a problem, for instance, when we try to use high-dose omega-3 fatty acids to reduce Lp(a) in the presence of apo E4.
As I commented above in response to Dr. Kruse's comments, as a practical matter I believe it is best to address the worst fraction of LDL particles first, i.e., take dietary steps to reduce small LDL particles, meaning reduce carbohydrate triggers of small LDL. Then deal with the large LDL that emerge by varying fat intake and gauging effect.
Odd thing: Even among apo E4 people, fat intake yields variable LDL-increasing effects, quite variable sometimes.
Also, recall that health extends beyond LDL. So there may be benefits to monounsaturates or omega-3 polyunsaturates, say, that extend to issues like brain and liver health.

Hi Melinda,
Please copy and post this in previous thread for ApoE4 … .
Continuation about ApoE4:
% of ApoE4 messes dynamic inside tissue cell so that ApoB turns to use Scavenger Receptors to try to start cascade which gets signal transducer (Specificity Protein 1) to up-regulate the cell membrane transporter protein ( ABCA1, ATP binding cassette transporter A1) that puts excess cholesterol out from that cell. I believe this is where Doc Davis’ stated ApoB irregularities add to the problem with ApoE4 (since normal human ApoE3 works all by itself to get that signal transducer to bind to ABCA1 to work shucking cholesterol) . When cholesterol gets to build up inside the cell the large LDL can acetylate and form excessive “droplets” in that cell’s cytoplasm; while the small LDL can oxidize from CuSO4- and load up inside that cell’s lysosome.

Meanwhile % of ApoE4 doesn’t just dock with tissue cell LDL receptors and so the macrophage scavenger receptors pick up too much cholesterol laden ApoB/ApoE lipo-protein carrier molecules. Once in the macrophage the same problem of oxidized LDL piling up in lysosome and acetylated LDL burdening cytoplasm occurs; and for that matter, in macrophages, it is down to ApoB to get the signal transducer going if any cholesterol is to be put out by cell membrane transporter protein ABCA1. This is the recipe for risky pro-atherogenic “foam cell” formation; while the individual genetics of ApoE, ApoB, assorted receptor types, signal transducer and transport protein all make it hard to predict how ApoE4 plays out.

Dr. Kruse broaches ApoE4 in alzheimers and this is in large part because ApoE4 causes the brain neurons to get less than optimal cholesterol from the brain’s astrocytes. It is ApoA1 working in HDL complex that controls the astrocyte cholesterol balance and when there is inflammation there is a risk of ApoA1 mis-folding to foster amyloid aggregations. Low intact ApoA1 and ApoE4 together increase the risk factor for cognitive problems and dementia several fold.

Diabetics with ApoE4 have that % of ApoE4 as an additional limitation; however, irregardless of the ApoE iso-form diabetic dementia risk arises from their glucose loads impairing kidney tubules, and thus fostering the uremic environment that stymies ApoA1 bio-synthesis. The normal role of ApoA1 is to bind to the transport protein which secures cholesterol into a safe bond with HDL; so low ApoA1 from any factor will challenge the brain neuron over time. I suggest there are individuals whose age impaired kidneys contribute to senile dementia from impairing ApoA1 levels being made and also possibly speeding up the normal 4-6 days kidney elimination of ApoA1 ; and so Patri’s comment on limitation of high protein intake is relevant due to it’s demand on aging kidneys.

Reply

The above comment was written by Might-o'chondri-Al.  He asked me to post it in this thread as he is having trouble posting here.

Ok I will test! But I have been asking around how to test and still don't know how? Is this something that I would just ask my doctor about? Maybe I go to the same lab that did my VAP? Since I got my results 3 weeks ago, I have made the following changes: zero bananas, reduced my cream intake by about 70% or so, lowered my overall fruit intake signigicantly, added 2 teaspoons of red palm oil daily, decreased caffeine intake (and now I am doing no coffee in August). I have also decided to eliminate all nuts and nut butters as of 2 days ago. Now my only real source of PUFA left in my diet is bacon, occassional chicken, and avocado. It's weird too, because on SAD, I was probably getting 10 times the PUFA, at least. I cooked in canola, ate loads of grain bread and corn products like tortillas. Maybe adding the saturated fats makes everything more amplified. The only thing now that I am VERY reluctant to give up is starches like potatoes and white rice. If I do, I will surely be VLC again, as I don't eat breads and very little fruit now, and rarely ever indulge in sweets. This means, by default, that most of my calories would then be sat and mono fats. Isn't that not good if I am ApoE4? What a mess! Dr Davis is right about being between a rock and a hard place. Jeez!

"high protein is not a healthy diet". you mean specifically for ApoE4 folks? I haven't been tested for it yet, but I suspect I may be ApoE4. I take whey protein daily and eat lots of eggs and beef. I do this on purpose because I do weight training 5x per week and am building muscle. Could it be true that people who are ApoE4 are not supposed to build much muscle? (logically speaking, due to the restriction on protein)

Is server cooperating now ?

ApoE4 degrades more readily than ApoE 3 or ApoE2; ApoE4 protein fragments that get into a tissue cell's cytosol can have bad effect on that cell's mitochondrial membrane lipid binding . This decreases the mitochondrial efficiency  when they try to perform glycolysis for generating energy.

ApoE4 degradation in a cell cytosol can  decrease the level at which that cell advances it's bio-genesis of  robust mitochondria; this is due to how ApoE4 fragments depresses PPAR gamma expression & PPAR gamma is what promotes making good mitochondria. (Specificly in the case of human fat tissue PPAR gamma is what regulates transcription of pre-adipocytes differentiation into true adipocytes. Hence Avandia & glitazone drugs that target the receptor of PPAR gamma do short out adipocyte differentiation;  and yet risk the side effect of increasing heart disease due to mitochondrial impairment.)

In Alzheimers the form of ApoE makes a difference; and the brain amyloids react to insulin differently with different ApoE iso-forms. The ratio of insulin in cerebro-spinal fluid as compared to insulin in plasma changes with different genotypes of ApoE.   Alzheimer patients tend to have lowered glucose utilization in their brains with  less insulin and insulin-like growth factor receptors, despite the Alzheimer brain harboring fewer insulin degrading enzymes. Which engenders a paradox whereby diabetic brain neuro-pathy experimentally improves with administration of nasal insulin; and similarly,  individuals  with ApoE4  receiving nasal insulin improved their cognitive function, with the boost being higher in ApoE4 carriers than folks with any other alleles of ApoE.

Higher amounts of Alzheimer amyloid  formed tangles are seen in Type 2 diabetics and in those with ApoE4; leading to the conclusion that "normal" ApoE3 fortuitously forms a complex with brain amyloids.
Apparently ApoE iso-forms other that ApoE4 can more readily bring an amyloid to where the molecule LRP-1 (lipo-protein related protein 1) can move that amyloid out across the brain blood barrier .

Hi Melinda,
Thanks for repost, looks like Doctor D hammered his server into shape again.

With regards to the large LDL content.  Again I am not a cardiologist, but a neurosurgeon.  The heart and brain work on the same principles of biochemistry.  And since these two organ take up much of the CO in the body they share much in common.  It is also why when we see neolithic disease affect the heart their is also a similar effect in the brain.  The Apoe4 story is one such case.  But so is the large LDL story.  Cardiology CW today believes that LDL matters.  In neurosurgery today its clear in neurodegenerative disorders we are lacking LDL and cholesterol more often than not.  This is incongruent to biochemistry.  Dr davis has said here in this thread the jury is out on large LDL in his field.  I am submitting that LDL matter little in any field.  Why?  If it did the body would have a specific detailed regulatory control method in place to deal with it and it does not.  In nature, with the consumption of organic, unprocessed parent essential fats rather than adulterated oils (PUFA's) and transfats, LDL cholesterol is supposed to be made up of significant amounts of properly functioning “parent” omega-6, linoleic acid (LA), and is not supposed to be harmful. It is the natural transporter of parent omega-6 and parent omega-3 into the cells. It is thus not critical to lower LDL cholesterol, nor is the absolute LDL number as important, if the diet contains sufficient unadulterated parent essential fats. These are unadultered PUFA's of both the omega 6 and 3 variety for clarity sake.  Also take note that the body has no natural “cholesterol sensor” in the bloodstream—it would if its levels had to be maintained within exact limits; such as, sodium, calcium, and glucose levels are monitored in many systems. For example, glucose levels are maintained to an amazingly tight 0.1% in each of us!  So Nature implemented biological mechanisms if required. There is no need for a cholesterol sensor because the absolute number is irrelevant.  That was my advice to Jack Kronk three weeks ago when he posted his VAP numbers and when I blogged about his numbers.  I understand that Dr Davis may not want to go out on a limb as I have here.  But I dont view it as a limb when the biology and biochemistry support my beliefs fully that LDL cholesterol levels are completely irrelevant to heart disease propagation.  This is why I advocate copious amounts of coconut oil to patients with heart disease and all neurodegenerative disorders including brain tumors and seizure patients.  In fact, my literature is loaded with thousands of papers supporting my belief made here.  I think its long over do that cardiologists start reading "other pathways" of data to reach conclusions that their own field muddies.  As a neurosurgeon, I read Dr Davis literature quite a lot and in comparing the two it is clear that our two fields are on a collision course from two different paths.  I got extreme clarity reading circulation over the last thirty years that cholesterol has nothing to do with heart disease.  Dr Davis has reach conclusions that are quite different from most of his fellow cardiologist as well.  I applaud him.  I just think he is still caught in the lipid hypothesis nightmare and that is the only reason he is not traveling down the road with me in unison.  Since he is a fine doc and one who clearly is ahead of his peers......i'll gladly wait for him on that road because we need him to alter what ails his branch of medicine to get to where we both need to be going for all patients.

Dr. Kruse,

What is your response to the fact that people with familial hypercholesterolemia (FH) have an exaggerated risk of CVD versus those who are not lacking ldl receptors? Why do so many of them have cardiac events in their 20's and 30's? Surely, you would not relegate this phenomenon to increased consumption of PUFA's and/or higher insulin?

There are five major classes of FH due to LDLR mutations.  FH is a collection of genetic defects.  Many believe that the end result of these defects (IE high LDL or cholesterol) cause the diseases associated with it.  I do not.  Why?  When these people live past their 6th decade they have extremely low levels of neurodegeneration.  I believe the cause of the early on set  CAD is tied to secondary effects of what the primary genetic disease does to the liver to alter its function.  If one looks at FH patients and their VAP results one sees a pattern of chronic gut inflammation that is the real source of the atherosclerosis that causes higher incidences we see in FH.   These patients all have altered gut biofilms and some of the lowest levels of Vit K2 and vit D.  They also have extremely low DHEA S and pregnenolone levels are pointing to a chronic inflammation......due not to the high cholesterol level but to an altered gut axis.  Read my blog on this here.    http://jackkruse.com/your-vap-brain-love-not-war/   My views on this topic are radically different because even with severe LDL lowering treatments the disease patterns these people face remain unchanged.  Why?  because their gut remains the source of the inflammation that damages their arteries for their entire life.  We need to focus our efforts on the gut side of the equation and not the LDL side.  Ironically Dr Davis has done this with his assault on wheat.  Wheat drives sdLDL via what mechanism?  It screws up the liver and increases gut permeability to cause issues.  His current ideas and mine are very close.......but no one is tying this together.  I think my VAP post on the gut provides you the link.

Genetic high total cholesterol is related to the over 50 amino acid variations of PCSK9 (pro-protein conertase subtilisn/kexin 9,  which comprises 692 amino acids). Individuals producing an excess of PCSK9 more extensively degrade their cholesterol receptors with surface defects; and so don't readily take up LDL out of circulation, which lets blood levels of LDL rise higher. Conversely, those making sparse PCSK9 can't degrade their LDL receptors, which pull lots of cholesterol into a tissue cell where it can pile up over time in that cell's lysosome; and blood levels of LDL seem to drop.


PCSK9's worst version is D3744; where total cholesterol trends to 4 times normal and risk of death is estimated to be even +/- 10 years sooner than even other problematic PCSK9 genetic variations that affect maybe 1 in 500 westerners and account for +/- 5% of all pre-mature coronary heart disease. As regards the "older" age survival ability of those with familial high cholesterol  this may be due to the way over time plaque holds less lipid content and acquires more collagen with calcium infiltration. In other words younger plaque is less stable and more likely to burst free and be perilous.

If fretting about plaque be aware that the average duration of carotid plaque is +/- 9.6 years; according to Carbon 14 dating from autopsies. Plaque may even form multiple times during one's life and the statistically dangerous symptoms take 5 - 15 years to manifest. Increased levels of circulating plasma insulin accelerate the rate that plaque forms; and also adds to a plaques instability (ie: potential to rupture) due to insulin's interaction with genes involved in the immune response;  like how those with insulin resistance make more pro-inflammatory cytokines. This bolsters Doc Davis' insistance to control glucose, since the down stream result is a more stable plaque.

Noteably, there is the so called "protective cytokine" TGF beta which can allay plaque rupture. This is hard to predict for individuals because we have no way to assess who has what types of TGF beta receptors around , since normal and then plaque ridden blood vessels can harbor different TGF beta receptors. TGF  is considered a vital player inside vascular smooth muscle cells because it forms part of the interactive sequence that stops the smooth muscle cells from altering; and it bears mentioning that excess cholesterol can inhibit some TGF beta pathways.

For those who asked (Jack Kronk, Peggy, et.al.) about where and how one can get tested for ApoE it's simple:   Virtually any large commercial lab in the U.S. can do the test, e.g., Labcorp, Quest, etc.   Also, Atherotech (VAP) and Berkeley Heart Labs will do the test as well.   Since it's a genetic test, it's only run once during a person's lifetime.  The test can run anywhere from around $100 on up, depending on which lab runs it for you.

In my last lipotropen test, I do not absorb chol not do I make it.  Am I a closed system?  My lp[a] is 41.  I am very puzzled.

Dee

That was from the Boston Heart lab.  I am a AP03/3.

Super interesting!

Do you know what SNP is PCSK9 ?  I'd like to look up it in my 23andme info.
Thanks,
George

Plasma PCSK9 levels correlate with cholesterol in men but not in women
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References and further reading may be available for this article. To view references and further reading you must purchase this article.


Janice Maynea, , , Angela Raymonda, Anna Chaplinb, Marion Cousinsb, Nadine Kaefera, Charles Gyamera-Acheamponga, Nabil G. Seidahc, Majambu Mbikaya, Michel Chrétiena and Teik Chye Ooia, b

aHormones, Growth and Development Program, Ottawa Health Research Institute, The Ottawa Hospital, University of Ottawa, Ottawa, Ont., Canada

bClinical Research Laboratory, Division of Endocrinology and Metabolism, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ont., Canada

cLaboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Que., Canada

Received 29 June 2007.  Available online 18 July 2007.

Abstract
Proprotein convertase subtilisin kexin-like 9 (PCSK9) is a secreted glycoprotein that negatively regulates low density lipoprotein receptor (LDLR) levels. Several single nucleotide polymorphisms (SNPs) in PCSK9 have been linked to autosomal dominant hypercholesterolemia (ADH). Conversely, hypocholesterolemia associates with both ‘loss of function’ nonsense and missense SNPs in PCSK9. We examined the association of plasma PCSK9 with lipoprotein parameters in 182 normolipidemics. For men (n = 98) plasma PCSK9 averaged 6.08 ± 1.96 μg/ml and Spearman analysis revealed significant correlation between it and total cholesterol (TC), LDLC, and TC/high density lipoprotein (HDLC) (r = 0.276, 0.282, and 0.228, respectively). For women (n = 84) plasma PCSK9 averaged 6.46 ± 1.99 μg/ml having no correlation with TC, LDLC or TC/HDLC. The ratio of plasma PCSK9/LDLC increased in men carrying ‘loss of function’ PCSK9 variations. Our results suggest a gender difference in PCSK9 regulation and function with PCSK9 correlated to TC and LDLC in men but not women.

Keywords: Plasma PCSK9; Loss of function; Hypocholesterolemia; Hypercholesterolemia; Single nucleotide polymorphisms

Article Outline
Materials and methods
dI found this on the internet, I'm not sure if this is what you need?  

Dee

All patients with FH need to have their thyroid optimized.  This issue was hashed out at the Ancestral Health Symposium on August fifth at UCLA.  Jack Kronk's VAP is helping many patients learn how to raise their HDL to increase endotoxin clearance from the portal circulation to prevent oxidation of slow moving cholesterol because of A lack of their LDL receptor.  Thyroid optimization can overcome this to a degree but it requires a physician who knows precisely how to do this and not create an unsafe situation.  Their diets has to be a strict low carb moderate protein paleo diet high in coconut oil.

This too can be assessed by looking at thyroid beta receptors......it is associated with down regulation or resistance of this specific thyroid receptor.  A company in Denmark has a clinical trial on going about this specific receptor.  Thyroid hormones bing to both thyroid alpha and beta receptors.  But disease that affect the LDL receptors seem to preferentially knock out the thyroid beta receptor.

I apologize if I sent the wrong ifo.  Didn't read it through.
Dee

Dr K. -

I am inquiring with the my Doc about getting tested for ApoE. I will let you know how that goes.

Regarding hypothyroidism, yah the issue that I'm running into is that "it requires a physician who knows precisely how to do this and not create an unsafe situation".

This is the problem with our medical system in America. I live in San Diego, one of the biggest, most advanced cities on earth, and I am having trouble finding anyone over here that can truly help me with this. My doctor situaiton is pathetic. Sorry to say that, but I'll call a spade a spade. All they want to do is put me on Lipitor and go low fat whole grain. So then I am stuck with doing my own diligent research, and appyling knowledge that I can learn from people who actually know what they are talking about, and right now, for me, that means the internet. Incredible when you think about it.

When you say low carb, do you mean no starch as well, not even potatoes? By the way... the name of this post is "The Exception to Low Carb". So... that's why this is so confusing. Some very knowledgable people think it's best to raise my intake of starches and lower my fats. If my body is creating more LDL (even small dense) because of my saturated fat intake, then it makes sense to replace sat fats with something else. I already get enough protein, so then I am left with carbs. If it has to be carbs, isn't safe starch my only real option? It can't be 'sugar'. It can't be 'fructose', or grain starch, right? Should I eat loads of salads? Or I am on the wrong track completely? Should I look at upping my mono fats in place of saturated, like using mac nut oil for cooking? Or would mono fats be just as problematic?

You see? Honestly, I know this stuff stone cold. I know what *most* people do well with, but if we don't figure out how being pre-disposed to having issues with LDL receptors really changes things, we are going to (deservedly) get hammered by the low-fat whole grain camp when a fair amount of people who thought they had it all figured out are dropping dead from eating fats because they are ApoE and had no idea.

I'm genuinely glad that my example is helping people. No doubt I am. But I'd be alright with feeling like I'm getting somewhere with all this in my personal case as well. At the moment, I can't really say that I feel that way just yet.

Patients with apoe4 have a higher rate of AD and AD is associated with a cholesterol deficiency in the brain.  So for me apoe4 is a signal to load with the MCT of coconut oil which has massive benefits to the brain metabolically.  I find it hard to believe this is bad for the heart at any level because CAD tends to mirror CVD across all measures.  I think only cardiologist have this problem with Larger particle LDL because of the faulty lipid hypothesis.  cAD is an inflammatory condition.  It ha little to do with cholesterol itself.  If the cholesterol is oxidized then there are issues but this can be followed by acute phase reactants from the liver like HS CRP.  When it's up HDL tends to be low......and it's low because the liver is being bombard by gut endotoxins and this is a direct measure of the oxidation potential of an overwhelmed portal circulation.  To further the point......thyroid hormone, testosterone, estrogen, and high vitamin D levels all raise liver HDL and this is how they protect against heart disease.  I maintain large LDL confers no risk without inflammation.......and a low HDL is a great way to know if your liver is being overwhelmed in the portal circulation.  This is why vitamin K2 confers a great cardiac benefit.......it comes from a healthy gut biome.  vAP tells you a ton about your portal circulations inflammatory burden.

M-Al, just copy your text prior to the post, or write it in the editor. I don't know which browser you use, but in Chrome if you use "back" on "server error", it will return what you typed in a reply.

Following your diet I took an NMR last summer and this summer.  The small LDL particles went down (835 to 709) but the total particles went up (1800 to 2100).  Should I stick with your diet (low carb, no wheat, D, omega3's), one Walmart glucometer) or go back to rice and beans?

I got quote at $390 for just an ApoE genetic test. Is that normal?

Have you seen any reduction in your LDL following this diet?

I've been eating paleo/primal for about a year, dropped 10 pounds, and brought my triglycerides down from a high of 325 three years ago to 130. Unfortunately, my LDL-p is over 2600 (first time it was checked), and I found out I'm APO e4/e4.

The doctor says e4/e4 should go vegan, which seems about as anti-primal as you can get.

Any suggestions for where to start looking for eating guidelines?

My goodness, how very confusing!!  I'm hypothyroid.  My HDL is 95. My total C is 285. Ny LDL is 186. But my LDL fractions are mostly big and plumb and my small total 23. So, I think I'm ok...buy my doc thinks I should go vegan. I want coconut oil, little red meat.  I evercise 5x week. My heatt stress tests were all 'well within'   So, it sounds as though I need to get the E4 tested   More?

I would be deeply grateful for your advice. I am doing my best to understand how to cope with my aPOE 3/4 status. I have Alzheimer's on both sides of my family, which has killed or is in the process of killing several relatives, including my father and maternal grandmother. Unsurprisingly, I have received much conflicting data.

I am 46. I eat a strict Paleo diet (grass-fed, wild-caught, etc.) except for some resistant starch in the form of parboiled rice and unmodified potato starch. I consume approximately 50-60% fats (majority saturated fats including daily MCT oil), 30-40% protein and 10-20% carbs. I exercise vigorously and non-vigorously -- but not every day. (Incidentally, over three years I naturally increased my testosterone by 38% using this approach, going from the low 3's to 5.3.)

My LDL is 128. My HDL is a distressingly low 33. Triglycerides are 59.

MY NEXT MOVE: Seek out an LDL particle-size test. If that reveals my LDL particles to be of an unhealthy size then I will need to consider a different approach in regard to sat fats. Also, looking  to improve my sleep, which has been my Achilles' heel (consistently get only around six hours). Finally, using super-consistent exercise and increasing oyster intake to boost the HDL.

I would appreciate any guidance.(!)

Best / Mario