PRIMER: An introduction to ApoE4, biochemistry, and possible prevention strategies

A primer for newbies and old pros alike.
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Re: An introduction to ApoE4, biochemistry, and possible prevention strategies

Postby Stavia » Mon Jun 15, 2015 10:13 pm

so...we don't have 60 years to wait for effects of interventions, so we have looked for surrogates to test theories.

There are two main places we can test - in vitro ("in glass") which means in a laboratory using cell cultures or chemicals - and in vivo (" in life") which, in a laboratory situation, usually means in mice. Mice only live for a couple of years, and scientists have been able to modify them genetically to have the ApoE4 variant. Mice are very similar to us biochemically, but obviously we are still different, and what works in a mouse may not work in humans. Mice are used to test theories and drugs before they are tested in humans. We call this method a "mouse model". This has been extremely useful for scientists to work out how the very complicated biochemistry of the body works.

We need to be extremely careful not to prematurely extrapolate results of a mouse model trial to mean it will work in humans.


Digression for fun:
I'd like to introduce you to my favourite mouse model. The "Ob mouse" which has been genetically altered to be obese, it's brain doesn't sense "leptin" , which is the satiety hormone we all make to tell us we are full and should stop eating. We have learned a lot about obesity with working with this mouse model. 2017: I still think it is adorable.

ob mouse.png
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Re: An introduction to ApoE4, biochemistry, and possible prevention strategies

Postby Stavia » Mon Jun 15, 2015 10:22 pm

Lastly, before I get back to prevention strategies, I would like to introduce what should become your second motto in trawling through the evidence in your quest to find your very best strategy.
Your first motto should be "genetics is not destiny"
Your second one, which I would like you to use in assessing the evidence, is "correlation is not causation"

Let me explain by means of a silly example: the earth is warming over the last century. Pirates are becoming scarcer. Therefore pirates stopped global warming. We need more pirates!! Arr me hearties!!
arr.png


pirates.jpg


here is another cute one:

Spurious-Correlations-08-685x433.jpg


These are silly, but an illustration of how careful you need to be, look extremely carefully at the evidence the author of a supposed causal link is presenting and ask yourself - is this just correlation? What is the evidence?
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Re: An introduction to ApoE4, biochemistry, and possible prevention strategies

Postby Stavia » Mon Jun 15, 2015 10:37 pm

1. Lowering insulin resistance.
2. Exercise
3. Sleep
4. Stress management
5. Eating a healthy diet with heaps of micronutrients.
6. Cognitive enhancement
7. Social enhancement
8. Selected supplements
9. Reducing inflammation in your body.
10. Avoid Smoking
11. Avoid having high blood pressure
12. Avoid hitting your head hard enough to sustain a concussion



Ok, we have digressed enough and I now come to the next of our possible strategies: Sleep

Once AD has set in, sleep is often disturbed as a result of the brain not functioning optimally. However, there are also indications that lack of sleep might be a risk factor for AD. Many scientists and doctors thus promote optimal sleep as a possible strategy for prevention. Obviously there has been no RCT, but only observational data. But there are solid theories and some evidence that this is likely to be correct.
Here is a quote from a recent paper. To explain better, the authors are saying poor sleep itself may increase accumulation of Aβ, as many researchers think that Aβ is cleared during sleep. In addition, sleep apnoea (spelled apnea in the USA) is a risk factor for AD, as the low oxygen during periods of disturbed sleep is detrimental to the brain.


Curr Opin Psychiatry. 2014 Nov;27(6):478-83. doi: 10.1097/YCO.0000000000000106.
Impact of sleep on the risk of cognitive decline and dementia.
Spira AP1, Chen-Edinboro LP, Wu MN, Yaffe K.
Abstract
PURPOSE OF REVIEW:
Trouble falling or staying asleep, poor sleep quality, and short or long sleep duration are gaining attention as potential risk factors for cognitive decline and dementia, including Alzheimer's disease. Sleep-disordered breathing has also been linked to these outcomes. Here, we review recent observational and experimental studies investigating the effect of poor sleep on cognitive outcomes and Alzheimer's disease, and discuss possible mechanisms.
RECENT FINDINGS:
Observational studies with self-report and objective sleep measures (e.g. wrist actigraphy, polysomnography) support links between disturbed sleep and cognitive decline. Several recently published studies demonstrate associations between sleep variables and measures of Alzheimer's disease pathology, including cerebrospinal fluid measures of Aβ and PET measures of Aβ deposition. In addition, experimental studies suggest that sleep loss alters cerebrospinal fluid Aβ dynamics, decrements in slow-wave sleep may decrease the clearance of Aβ from the brain, and hypoxemia characteristic of sleep-disordered breathing increases Aβ production.
SUMMARY:
Findings indicate that poor sleep is a risk factor for cognitive decline and Alzheimer's disease. Although mechanisms underlying these associations are not yet clear, healthy sleep appears to play an important role in maintaining brain health with age, and may play a key role in Alzheimer's disease prevention


So what can you do to improve sleep quality?

1. Identify and treat sleep apnoea (spelt apnea in the USA) if present. Do you snore at night and stop breathing? Do you wake gasping for breath? Do you have daytime sleepiness? Do you fall asleep in a movie, watching TV, while reading, or at a red traffic light? Do you wake un-refreshed? Please discuss with your doctor.
2. Think very carefully about asking your doctor for sleeping tablets unless as a temporary measure. Hypnotics and benzodiazepines have been linked to a higher incidence of dementia - the risk is about 50% greater. This has been a consistent finding across the scientific literature
3. Melatonin however is thought to be safe for insomnia. There has been no reported increase in dementia with its use. However there is no evidence that it can prevent dementia when used by itself. I recommend small doses - starting at 0.5mg or 1mg. I have found it very useful in my work in the elderly with dementia and disturbed sleep patterns
4. General sleep hygiene measures
http://healthysleep.med.harvard.edu/healthy/getting/overcoming/tips
5. Body clock "hacks" such as blue-blocking glasses https://www.lowbluelights.com/. How these work is that our body clock is set by the colour of the light that hits our eyes. Blue light tells our brains it is day. As the sun sets and the natural light turns yellow, our brains sense it is night time soon and secrete melatonin. By watching TV, laptops, and using bright lights in our homes at night we unfortunately are confusing our brains to think it is still daytime.
yellow glasses.jpg

There are also apps for your phone like "twilight" and for your laptop called "f.lux".

Edit 2019: Here is a useful interview - Rhonda Patrick interviews Matt Walker. He discusses the 5 pillars of sleep optimisation: 1. Minimising blue light from screens and room lighting in the evenings; keeping the rooms temperature cool ie between 63 and 66degrees farenheit; not staying in bed in the night for more than 20 minutes if one wakes up; reducing alcohol; reducing caffeine and not having it past noon.
He is the author of the book Why we sleep

If you want to learn more about how our body clocks work I highly recommend this book
http://www.goodreads.com/book/show/13598053-internal-time

internal time.png


Glossary for Primerhttps://www.foundmyfitness.com/episodes/matthew-walker
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Re: An introduction to ApoE4, biochemistry, and possible prevention strategies

Postby Stavia » Tue Jun 16, 2015 1:43 pm

1. Lowering insulin resistance.
2. Exercise
3. Sleep
4. Stress management
5. Eating a healthy diet with heaps of micronutrients.
6. Cognitive enhancement
7. Social enhancement
8. Selected supplements
9. Reducing inflammation in your body.
10. Avoid Smoking
11. Avoid having high blood pressure
12. Avoid hitting your head hard enough to sustain a concussion



When we are stressed or worried, one of the body's physical responses is to increase production of a hormone called cortisol.
here is a nice quote from the Mayo Clinic:
When you encounter a perceived threat — a large dog barks at you during your morning walk, for instance — your hypothalamus, a tiny region at the base of your brain, sets off an alarm system in your body. Through a combination of nerve and hormonal signals, this system prompts your adrenal glands, located atop your kidneys, to release a surge of hormones, including adrenaline and cortisol.
Adrenaline increases your heart rate, elevates your blood pressure and boosts energy supplies. Cortisol, the primary stress hormone, increases sugars (glucose) in the bloodstream, enhances your brain's use of glucose and increases the availability of substances that repair tissues.
Cortisol also curbs functions that would be nonessential or detrimental in a fight-or-flight situation. It alters immune system responses and suppresses the digestive system, the reproductive system and growth processes. This complex natural alarm system also communicates with regions of your brain that control mood, motivation and fear.


This is all very good when the threat is real, eg running away from a saber tooth tiger. But as part of our everyday lives, all day, most days - this is not good.
The chronically elevated cortisol levels have many adverse effects. Of note is their effect on the brain, especially we think in the hippocampus - this is the part of the brain where memories are formed and stored. With constantly high levels of cortisol, the brain cells are less resilient to damaging factors in their environment, there are less connections being formed in the hippocampus, there are less new cells being produced in the hippocampus, and there is impaired creation of new memories and access to existing memories. The hippocampus can even shrink in size.
In addition chronically elevated cortisol levels have an adverse effect on glycaemic control. They will raise blood glucose levels, which we know isn't good.
Chronic stress can interfere with sleep which we have already discussed.
addition 2018: Searcher, one of our members, posted this excellent study which show an increase in effect of anti-inflammatory pathways with increased happiness. It's very interesting - happiness that comes from a sense of purpose in terms of meaningful and pro-social goals, rather than self-gratifying hedonism appears to switch off inflammatory genes at DNA level. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4374902/
Addition 2018: here is a wonderful wiki article written by Theresa for our community
https://www.apoe4.info/wiki/Stress


so...what can you do to manage stress optimally?
Here are some options:
1. exercise is a great stress management strategy
2. meditation. My current favourite is Mindfulness meditation, developed by Jon Kabat-Zinn
https://en.wikipedia.org/wiki/Jon_Kabat-Zinn
http://www.mindfulnesscds.com/
There are many YouTube videos that you can access free. I personally use an app called Headspace which gives you access to 10 introductory 10 minute sessions free. https://www.headspace.com/
3. Prayer
4. Connect with the outdoors - go for a walk outside
5. Talk to a friend or family member or share your fears on the forum under "support"
6. Journal your concerns
7. Take a hot bath with bubbles and candles
8. Get yourself a massage, or mani-pedi, or facial
9. Have a lovely herbal tea
10. Listen to music
11. Watch a chick-flick or comedy movie
12. Edit 2018: get involved in charitable or environmental work, volunteer in neighbourhood or community ventures, (help us build this Apoe4 community!), etc

Glossary for Primer

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Re: An introduction to ApoE4, biochemistry, and possible prevention strategies

Postby Stavia » Tue Jun 16, 2015 4:21 pm

1. Lowering insulin resistance.
2. Exercise
3. Sleep
4. Stress management
5. Eating a healthy diet with heaps of micronutrients.
6. Cognitive enhancement
7. Social enhancement
8. Selected supplements
9. Reducing inflammation in your body.
10. Avoid Smoking
11. Avoid having high blood pressure
12. Avoid hitting your head hard enough to sustain a concussion


Now we get to an area that isn't that simple.
There is no controversy that a wide of variety of plant-based foods is beneficial for most people - see below for nuances .

There is no controversy that chemical-laden processed foods are not the best choice you can make.

There is no controversy that over-eating is not good.

What is not clear is what the optimal macronutrient balance is for e4s. Macronutrients are the protein, carbohydrates and fat in our diets.

I will discuss each one of these separately


Wide variety of plant based foods: Consistently studies have shown that a Mediterranean type diet reduces the risk of dementia. http://www.ncbi.nlm.nih.gov/pubmed/20182044. This doesn't mean lots of pizza and pasta - it means (broadly speaking, there are many variations) an emphasis on plant based foods, small amounts of animal protein (mainly fish, some chicken, little red meat), lots of olive oil (usually extra-virgin olive oil - called EVOO by us on the forum), nuts, whole grains, little bit of diary. No processed foods. It also doesn't mean huge chunks of bread with slabs of cheese and one lettuce leaf. It is thought that the wide variety of veggies is particularly protective. Plants contain many good compounds that we have not yet identified - and they are best taken in the natural form of a plant rather than a pill. I recommend that you "eat across the rainbow" and eat a wide variety of different coloured veggies and fruits. Leafy greens are particularly good, as are berries which can be eaten fresh or frozen http://healthland.time.com/2012/04/26/brain-food-berries-can-slow-cognitive-decline/. I would recommend that you limit your starchy veggies such as potato and sweet potato in order to maintain good glycaemic control, but eat freely of other veggies. Fruit is also good, but I recommend that you do not overeat fruit in order to maintain good glycaemic control. Two fruit portions a day for a small woman and three a day for a man are enough IMO. (a portion is the size of an apple, or half a cup of berries). I strive to have 80% of my plate at each meal as veggies, salad or veggie soup. Sometimes my lunch will be an entire head of broccoli and a small can of salmon for instance, with a some nuts afterwards.

A few good places to start are
the MIND diet https://www.rush.edu/news/press-releases/new-mind-diet-may-significantly-protect-against-alzheimers-disease

Dr Richard Isaacson's Alzheimers diet http://www.alzheimersdiet.com/

2017: IMO Dr Isaacson's book is still a good, easily understood, starting place, but I now (as of August 2017) recommend Dr Dale Bredesen's book in preference.
https://www.amazon.com/End-Alzheimers-P ... .+Bredesen


I do not recommend The Perfect Gene Diet. Here is my review https://www.apoe4.info/forums/viewtopic.php?f=6&t=697&p=6224&hilit=the+perfect+gene+diet#p6224

2017: More complex areas: There is a theory that some plants from the New World contain lectins that we have not evolved to cope with. This is best explained by Dr Stephen Gundry who feels it is particularly relevant in auto-immune disease - http://gundrymd.com/ - https://www.amazon.com/Plant-Paradox-Da ... nt+paradox - IMO there is at yet no evidence lectins are a major factor in Alzheimers Disease, but absence of evidence is not the same as evidence against. I remain open-minded. Dr Gundry recommends a vegetarian diet for those that chose this path.

There is much controversy around vegan and vegetarian diets. Here is Georgia Ede discussing effects of different diets on the brain. http://www.diagnosisdiet.com/vegan-diets-and-the-brain/


Chemical laden, processed foods: - many modern day diets are sad :( - in fact, the acronym is SAD or standard American diet. This diet puts people at much higher risk many of the modern chronic diseases: diabetes, heart disease, cancer and dementia.
SAD.png

The words of Michael Pollan (In Defence of Food) ring very true
http://www.goodreads.com/book/show/315425.In_Defense_of_Food
pollan.png


By "eat food" he means eat real food, not faux food made of many unpronounceable chemicals. "Mainly plants" we have discussed. And "not too much" is obvious, in the light of our discussion about obesity and IR. In a future post I will also discuss IF - or intermittent fasting. By this I mean eating at least a couple hours before bed, and not eating again for 12 hours. Many of us fast each day for longer than that, I eat around 6pm and again around 11-12ish, two meals a day (mainly plants :) ). Fasting reduces oxidative stress which happens when the normal by-products of a cell's functions produces more free radicals that can be neutralised by antioxidants and this imbalance damages cells http://www.iflscience.com/health-and-medicine/how-fasting-might-make-our-cells-more-resilient-stress and also generates ketones which our mitochondria can use for fuel (more on this later). Because I feel that the daily benefits of reduced oxidative stress and ketone production are important, I do not believe that intermittent fasting of the 5:2 variety is the best choice for us IF the 5 days' foods consists of unhealthy foods. However if you feel this would suit you better, 2 days reduced calories has also been shown to be beneficial, in conjunction with healthy choices the other 5 days.


And finally we get to optimal macronutrient composition of a diet: here is where the discussion - often heated - lies.
You will see that a lot of our discussion is around this area. This is not because we as a group think it is more important than other strategies, it is because it is a tricky and controversial area. Basically we are trying to balance a see saw of carbs vs fats, which translates into a see saw of glycaemic control (IR) and lipids. And it appears that we respond individually to different dietary compositions.

I will continue this in the next post

Glossary for Primer
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Re: An introduction to ApoE4, biochemistry, and possible prevention strategies

Postby Stavia » Sat Jun 20, 2015 2:22 pm

A macronutrient is fat or carbohydrate or protein. Macronutrient ratios are the proportion of % of each in the diet. There are several options here and each person has their own favourite. I would urge you to look at the evidence for each kind of % makeup, test the different ones on your own biomarkers (blood tests) such as glycaemic control and lipids (more later on this) and then decide which one suits you best. The two main options are high fat and low fat. High fat is also called LCHF or low carb high fat.
Here are two threads discussing the benefits of each
viewtopic.php?f=6&t=178
viewtopic.php?f=6&t=179

I wish to stress that I personally am not in any way advocating a high saturated fat diet (animal fat eg fatty meat, butter, lard) . I personally believe, based on my assessment of the evidence, that high saturated fat may be detrimental to e4s. (My reason is that e4s start with a higher baseline LDL, and high dietary saturated fat drives LDL synthesis at hepatocyte level, amongst other reasons. I believe, based on my interpretation of the evidence, that high numbers of LDL particles in the blood matters very much for many reasons). When I speak about high fat I am speaking about fat percentages of diet around 50%, and the fat primarily coming from fatty fish, nuts, avocados and EVOO (extra virgin olive oil). I personally am not sure about coconut oil yet, it may be neutral.
Addendun 2016: and a year later this is still unclear. Some experts advise e4s to avoid saturated fats, others say the opposite. I am sorry but IMO definitive evidence is just not here yet.
And...2017...still no clarity. I am as of August 2017 about to embark on a trial of 4 different diets - my usual, one very high fat, one very low fat, Gundry lectin avoidance - and let's see what happens to my biomarkers and well-being viewtopic.php?f=4&t=3299


We have already discussed proteins and carbohydrates, and I will get to fats shortly, in the next post. I will explain exactly what is the difference between saturated fats and cholesterol for instance.

How does one start designing a macronutrient framework?

I suggest you start with your protein. We need protein for essential body functions. We cannot synthesise it, we have to eat it. We cannot store protein at all. If we do not eat enough protein each day we will cannibalise our muscles to provide the amino acids we need each day just to keep our bodies functioning. This is obviously not good! And low muscle mass is a risk factor for AD. We discuss it in this thread, where Julie and Martha report on a conference in NYC recently viewtopic.php?f=4&t=1244&p=13719&hilit=sarcopenia#p13719
The word we use is sarcopaenia or sarcopenia in the US. Sarco means muscle. Paenia/penia means a scarcity of, or not enough.

In addition, we should avoid eating far too much protein - because remember I said we cannot store excess dietary protein? The excess gets turned into glucose by a process called gluconeogenesis (making=genesis new=neo ). If we do not burn that excess glucose soon, it will get stored as fat. Which is not a good thing. In addition, too much protein activates mTOR in the body, which is good for short periods of muscle bulking, but bad in excess and if sustained as it promotes aging of the cells and many chronic diseases including cancer: https://selfhacked.com/blog/mtor-natura ... nhibitors/

Please don't worry that you are on a knife edge here, there is leeway. A bit of extra glucose from excess protein won't harm. But a huge excess is unlikely to be healthy. I suggest you start with the mainstream 0.8gm -1gm/kg body weight. I know this is a very rough guide, it's just a start. I consider 2 grams protein daily/kg body weight to be excessive in a person not doing heavy body building, as I consider that the excess from gluconeogenesis will start to impact and sustained mTOR ativation is a risk.

Now you need to know for instance that a gram of salmon is not a gram of protein. 100grams of salmon has around 25 grams of protein. You will need to use a calculator such as Cron-o-Meter to work it out. Here is a link with some examples.
http://www.healthaliciousness.com/artic ... rotein.php

Everyone is a different body weight and requires different calories to maintain a healthy body weight : for instance look and me and Julie - I can only eat 1200 calories a day to keep trim. I weigh 62 kg (2017: 66kg), so at 1gm/kg my protein requirements are 62 grams, (2017: now I try and keep it at 40-50grams a day). I am naturally muscular and short. There are 4 calories per gram of protein, so this is 248 calories from protein. 248/1200 = 20% of my daily calories come from protein in my diet.
Julie needs 1700 calories not to get too thin. I think she weighs around 55kgs (she is gorgeously tall and lean like a gazelle). Her protein requirements are around 55 grams. This is 220 calories. It is only 12%. She actually eats more protein than this as she is aiming at building more muscle, but you get the idea - that it is inaccurate to use a one size fits all percentage.

If this is too complicated to track, I suggest you start with 20% protein .

Then I suggest you next look at your carbohydrates. In the interest of maintaining great glycaemic control, I recommend being prudent with how much carbohydrates we eat. Some people are extremely active and burn off their carbs really fast, and they will be able to tolerate a much higher carbohydrate load daily. For instance there are a few remaining hunter gatherer populations who eat up to 70% carbohydrates. However one needs to be careful in extrapolating this situation to our current modern day life where we are not as lean, not as active, and eat a much narrower variety of plants. In addition there are very low fat, high carbohydrate vegan diets that appear to be beneficial for longevity and chronic disease. I do not have any experience about these, if anyone on the forum knows about them, PLEASE start a thread and discuss how they work.

You will need to work out for yourself where your optimal carbohydrate intake lies. I suggest a good way to track is to count the grams per day, again via Cron-O meter. I suggest you ease them down slowly and see how your body and biomarkers (markers of IR and also lipids) respond. I try to keep my carbs under 100 grams a day, and am currently trialling a lower amount, down to 70 grams In 2017 I am now under 50 grams and doing well. At 100 grams carbs a day, this is 400 calories, or 30% of my total calories. So If 20% of my diet is protein, 30% carbs - then the remaining 50% of my calories must be from fat. Which brings us to our next digression.

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Re: An introduction to ApoE4, biochemistry, and possible prevention strategies

Postby Stavia » Sat Jun 20, 2015 2:35 pm

Fats aka lipids

This is a horrendously complex topic. Here is a thread to show you how much I am simplifying this
viewtopic.php?f=30&t=1197&start=50

images.jpg


Please read very very carefully so that you are not mislead by inaccurate internet blogs or media articles written by people who don't understand the details.
This is so critical that this message has its own post.
Don't be scared - I will start very gently.
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Re: An introduction to ApoE4, biochemistry, and possible prevention strategies

Postby Stavia » Sat Jun 20, 2015 2:41 pm

And my second critical message

GLYCAEMIC CONTROL TRUMPS LIPIDS, EVERY TIME
You have been dealt a hand of cards. You need to play them cleverly.

untitled.png


IR is far more damaging than a high LDL, but LDL still matters. We are on a seesaw trying to balance these two. The balance point will be different in everyone.
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Re: An introduction to ApoE4, biochemistry, and possible prevention strategies

Postby Stavia » Sat Jun 20, 2015 2:56 pm

Remember I said that there were four main group of large molecules (macromolecules) that are the building blocks of our bodies? We have already discussed proteins and carbohydrates. The next is lipids which we loosely (and strictly incorrectly) call fats. (The last is nucleic acids, ie DNA and RNA)

There are various kinds of lipids, and they are all totally different in structure and function.
I will discuss the four most important kinds to start you off. There are others. I will discuss sterols, fatty acids, triglycerides and phospholipids.
If you wish to know more, here is a thread where we explored some details about fats, it includes finer details about fats/lipids
viewtopic.php?f=6&t=1305
Once you understand my explanation below, you might want to browse through it.
But I will start much simpler:

FIRST IMPORTANT KIND OF LIPID: STEROLS
Sterols are characterised by their ring shape. Here is a picture. The points of the ring are carbon atoms, we just don't write a C at the corners, because carbon is the only atom that can form this ring. When we see this ring, we know it is carbons always.
300px-Sterol_svg.png

The most important sterol molecule is cholesterol. It is critical in many body functions.
Cholesterol is a zoosterol. Zoo means from animals. This is opposed to phytosterols which plants make. All cells in animal bodies can make their own cholesterol. The liver cells are the best at making it. 80 to 85% of the cholesterol in our bodies is from liver cell production which gets into the blood in a complicated way. Some of it goes into the intestines through the bile and is reabsorbed again. It can circulate several times through this cycle. Some of it directly goes into the blood. Cholesterol derived from our food has minimal effect on our blood levels of cholesterol. I repeat, you cannot significantly reduce your blood cholesterol by limiting food cholesterol (within reason). Internationally the current recommendation is that dietary cholesterol does not need to be limited (within reason). (please read the whole post before understanding that cholesterol is not the same as saturated fat, or other fat. I will explain what the real meaning of the word fat is shortly. It is actually the scientific name for triglyceride and has absolutely nothing to do with cholesterol molecules).
This means that, like bowties, eggs are (within reason) cool (but careful, each egg has 1.5grams saturated fat, it can add up)
I suggest you have a look on google how much cholesterol and how much saturated fat your preferred foods contain. And in 2017 we finally have the first female Dr Who ! She was brilliant in Broadchurch - I highly recommend it.

images9B8I2OT5.jpg


So if dietary cholesterol has very little impact on the amount of cholesterol in our blood, why are the little packages carrying it (called LDL, more later) so high in the blood of some people? Well, various things happen, but the simplest way to explain is to say that the liver is making too much. Why? reasons include genetic factors, too much saturated fat in the diet which in a complicated way drives the liver to make more, and also IR can drive more LDL packages to be made. So here is where glycaemic control has a direct impact on lipids. The reason it does this is that excess glucose that isn't burnt up by the body is converted into triglycerides (the real fat) by the body and sent off to the fat cells to be stored. They have to be packaged somehow, they can't dissolve in the blood. They are packaged in little packets called LDL together with cholesterol.

ldl.jpg

This LDL that you see on your blood test is traditionally called bad cholesterol but it is much more complicated than that. The LDL particle is a package containing various amounts of cholesterol and triglycerides. It comes in various sizes. Its envelope holds in the cholesterol and triglycerides. The particles can be a variety of sizes up to a maximum. For a given amount of cholesterol that needs to be transported in the blood, the number of the particle will depend on how much triglycerides also need to be transported. If there is a lot of triglyceride around, you will need more particles for a given amount of cholesterol. So looking at a regular blood test, for a given value of LDL cholesterol, you have no idea how many particles that is comprised of. (We can get an idea by looking at the triglycerides in the same test - high is bad). The greater number of particles you have in your blood, the higher is your cardiovascular risk. There can be tons of teeny particles (currently considered to be bad) or a few large particles (currently considered to be good). The field of lipids (called lipidology) is very complex and still somewhat controversial. The science if not settled, and it is certainly not black and white. The tendency of the press and doctors to oversimplify gives the false dichotomy of good versus bad. Lipids are very complex and nuanced and digging deeper, the impression that high is bad and low is good, is totally false. However, there is no controversy that high triglycerides, as measured on a lipid panel, are detrimental. The controversy and the unknowns are in the field of the LDL and LDL-subparticles.


untitled.png


Each little packet or particle has one special molecule called apolipoprotein-b on its surface, so this is one way of measuring how many particles there actually are. (A good number here is under 100). Another way is NMR, a special test that counts the particles. Here the number you are looking at is the LDL-p value. (We like to aim for under 1200)

So to summarise: cholesterol is one kind of lipid molecule. It has absolutely completely different to saturated fat. You need to check the different amount of cholesterol and saturated fats in your preferred foods. They are completely different. It is vital to the functioning of our bodies in many different ways. Most of the cholesterol in our body is made by our livers. Restricting cholesterol from food does not significantly change the cholesterol level in our blood. Cholesterol is carried in little packages called LDL together with triglycerides. We like to have a low number of these little packages to lower our cardiovascular risk.

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Re: An introduction to ApoE4, biochemistry, and possible prevention strategies

Postby Stavia » Sat Jun 20, 2015 4:36 pm

SECOND IMPORTANT KIND OF LIPID: FATTY ACIDS

here is a skeleton of the terms we will be discussing:
1. saturated fatty acids (aka sat fat)
2. monounsaturated fatty acids (aka MUFA)
3. polyunsaturated fatty acids (aka PUFA)
a. omega3 fatty acids
b. omega6 fatty acids

Fatty acids are long chains of carbon molecules. Remember carbohydrates are chains as well, but fatty acids are differently structured. Each carbon atom in the chain can "bond" with four other atoms. I like to visualise this as 4 hands available to hold with another hand. A hand is never alone not holding on, that makes the molecule unstable.

The carbons in the chain can hold each other with one hand only, which means once they have a hand to each neighbour (each of these hand holdings is called a "single bond"), they have two hands free. These two hands usually hold onto a hydrogen each. (a hydrogen only has one hand). If all the carbon atoms are holding onto their carbon neighbours with only one hand, and has a hydrogen on each of its other two hands, the fatty acid is called "saturated". This means that you cannot possibly add any more hydrogen atoms, the chain is full or "saturated" with hydrogen atoms. Saturated fats come in different lengths - they range from 4 carbons long right up to 36 carbon atoms long. They have different names. https://en.wikipedia.org/wiki/List_of_s ... atty_acids
We mainly eat the ones from 4 to 18 carbon atoms long.
Butyric acid with 4 carbon atoms (contained in butter)
Lauric acid with 12 carbon atoms (contained in coconut oil, palm kernel oil, and breast milk)
Myristic acid with 14 carbon atoms (contained in cow's milk and dairy products)
Palmitic acid with 16 carbon atoms (contained in palm oil and meat)
Stearic acid with 18 carbon atoms (also contained in meat and cocoa butter)
https://en.wikipedia.org/wiki/Saturated_fat
The different effects of different saturated fats is beyond the scope of this basic guide. It is extremely complex.
http://ajcn.nutrition.org/content/65/5/1617S.abstract
You will find more discussion in our forum.
Here is one article that links saturated fat intake to dementia
http://www.neurobiologyofaging.org/arti ... 97-4580(14)00355-8/abstract?cc=y=

2017: I am fully aware that this particular facet is controversial, and I am stating my interpretation of the evidence, which resonates with many top Alzheimer's clinician's opinions and that of many of our members. I am not promoting a high saturated fat diet, and our forum is not promoting a high saturated fat diet either. Mainstream recommendations are to limit saturated fat to 7% or less of calories and I see no compelling evidence that is contrary to this. I am fully aware that there are those who believe that high saturated fat is benign. In the absence of compelling evidence to support this, ie reduced risk of AD and CVD with high saturated fat (not surrogate markers such as a LDL level, I want to see numbers of actual dementia and actual heart attacks, and with clear causation, not correlation), I chose to limit my saturated fat and so do many on the forum. However, others disagree.


If there is one pair of carbons who are holding each other with two hands, there will be what we call a "double bond" between these two carbons. This chain is thus capable of holding hands with more hydrogens that it is actually doing. It is thus not fully saturated with hydrogen. It is "unsaturated".

If there is only one pair doing this, we have a "mono-unsaturated fatty acid". We call these MUFAs for short. https://en.wikipedia.org/?title=Monounsaturated_fat
These are found in foods such as olives, olive oil, avocados, nuts and are shown to reduce LDL amongst other functions.

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If there is more than one pair doing this, we will these "polyunsaturated fatty acids" or PUFAs. There are two important kinds of PUFA's - omega 3's and omega 6's.
https://en.wikipedia.org/wiki/Polyunsaturated_fat
Omega-3s are thought to be particularly protective for us for many reasons. the two most important kinds for us are DHA and EPA. I believe we should aim for 1.5grams of combined DHA and EPA in our diets, either from food, supplements or a combination. This is just a rough guide to start. They can be obtained from fish, vegetable oils, nuts (especially walnuts), flax seeds, flaxseed oil, and leafy vegetables. https://en.wikipedia.org/wiki/Omega-3_fatty_acid
Here is a diagram of DHA, our most important omega3 fatty acid

360px-DHAnumbering.png


Omega-6s are still important but it appears that the balance between 6 and 3 might be important in reducing inflammation. This is not yet fully a mainstream medical belief but is fast becoming widely accepted. I believe it is true, in my interpretation of the evidence. It is suggested that we should aim for a ratio of 3:1 maximum in our 6:3 ratio. I try to aim for 1:1 or 2:1. (The SAD has ratios of 20:1). They are obtained from nuts for instance (where they are combined with omega 3's thus this is not an issue), and industrial seed oils - this means that the fries you ate where most likely fried in a vegetable oil such and this delivered a massive dose of omega 6's to your body. have a look at this link please http://www.healthaliciousness.com/artic ... -foods.php
Food companies are sneaky. They only care about profits. They are deliberately misleading you context-wise by saying that their products are low in saturated fats and high in polyunsaturated fats. They are insinuating that the product is super healthy. PUFAs are not all equal. The devil is in the detail.

Glossary for Primer
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