Lipoproteins & apolipoproteins: E, by 'eck.

In December 2008, I wrote about Cholesterol And Coronary Heart Disease , where I used a limousine metaphor to describe how cholesterol & fat are transported around the body. Here's a diagram of a chylomicron lipoprotein "limousine". Chylomicrons transport dietary fat (triglycerides) & cholesterol from the gut to the liver & other tissues. As there's much more dietary fat than cholesterol, the contents are mostly fat.

A chylomicron. T=Triglyceride C=Cholesterol. From http://en.wikipedia.org/wiki/Lipoprotein

The lipoprotein "limousines" vary a lot in size.

(a) VLDL (b) chylomicrons (c) LDL (d) HDL. 
From http://healthcorrelator.blogspot.co.uk/2011/11/triglycerides-vldl-and-industrial.html

Apolipoproteins are the "chauffeurs" which determine to where lipoproteins transport stuff.
Apo A is found mainly on HDL, which transports fat & cholesterol from tissues to the liver.
Apo B is found mainly on LDL, which transports cholesterol from the liver to tissues.
Apo C is found on HDL when fasted, but moves to chylomicrons & VLDL when fat is eaten.
Apo D is found mainly on HDL and is is associated with an enzyme involved in lipoprotein metabolism.
Apo E is found mainly on chylomicrons & IDL and transports lipoproteins, fat-soluble vitamins, and cholesterol into the lymph system and into the blood. In the CNS, Apo E transports cholesterol to neurons. Defects in Apo E result in hyperlipidaemia , cardiovascular & neurological diseases, and is the E referred to in the title.

There's also Apo H, which is a β-glycoprotein involved in the binding of cardiolipin. It has nothing to do with the above lipoproteins.

Completing the trine: Which are the safest fats?

First, watch this video by Chris Masterjohn.

Diets very high in pufas (polyunsaturates) are not beneficial to heart health or longevity. Flora? No thanks!

Here's a chart. The beige & grey bars represent pufas (omega-6 & omega-3).

Comparison of dietary fats

The yellow bars represent monounsaturates and the orangey-red bars represent saturates. I consider these to be harmless, as long as you don't go mad and eat them in such large amounts that you gain weight.

Bearing in mind the information in the video, plus the information in Fats: Spawn of Satan or Dogs' Doodads? , I use only fats from the bottom 6 for cooking (olive oil and butter, actually).

Flaxseed oil can be used as an omega-3 supplement for vegetarian/vegan women, as omega-3 pufas are as rare as rocking-horse poo in most foods (apart from oily fish).

Non-vegetarian/vegan people can get their long-chain omega-3 pufas (EPA & DHA) from oily fish. As vegetarian/vegan men barely produce any DHA from the omega-3 in flaxseed oil, they should get it from algal DHA supplements. See Extremely Limited Synthesis of Long Chain Polyunsaturates in Adults: Implications for their Dietary Essentiality and use as Supplements.

The danger of science denial: It happens even on Science-Based blogs.

Poor Benjamin Franklin. I know how he felt! ;-)

I do not believe that he wanted to be doing that!

This post will be highly critical of Dr. David Gorski MD, as some of his comments have been either trolling, downright stupid, or both. They're definitely in denial of science. This post is intended to encourage Dr Gorski to leave comments here, as I will never leave any further comments on any blogs that he edits, for reasons mentioned previously. I will be copying comments from his blogs and pasting them here, with my comments after. If this is considered to be "bad form", I really don't care. Leaving derogatory comments about me on blogs on which the commenters know that I will never return (because I told them so) is definitely "bad form".

I will also be quoting other commenters on Dr Gorski's blog, for the same reason. Everyone is free to leave comments here, that meet my fairly lax moderation criteria. In Vitamin D, cancer, cliques and flouncing. , a commenter from Dr Gorski's blog called flip was initially whitelisted, to allow his comments to appear without me having to moderate them. I eventually blacklisted flip after I detected intellectual dishonesty. That's how I roll. If you don't like my rules, don't let the door hit you on the way out! By the way, calling me a liar on here is a sure-fire way to get yourself blacklisted.

I've just turned Blogger word verification back on, as although Disqus automatically deletes anonymous comments containing links, I still get email notification of them. I've been getting a lot of email notifications. This may or may not have an effect on commenters.

Firstly, please read http://www.sciencebasedmedicine.org/index.php/a-closer-look-at-vitamin-injections/#comment-127850 , as it's my "letter of resignation" from that blog. With that in mind, read on.

# David Gorski on 27 May 2013 at 9:49 am
Regarding Lappe et al, one notes that that study is not the be-all and end-all of vitamin D research. It’s an old study, for one thing. Also, cancer was not its primary endpoint. Finally, there was no vitamin D alone group, as I recall, only a vitamin D + calcium group, a calcium group, and a placebo group.
There is a recent review of the literature from the Endocrine Society, which includes Lappe et al and puts it into context:
*quoted text redacted*

# Nigel Kinbrum on 27 May 2013 at 11:16 am
David Gorski said…

Regarding Lappe et al, one notes that that study is not the be-all and end-all of vitamin D research. It’s an old study, for one thing.

Irrelevant.

Also, cancer was not its primary endpoint.

Irrelevant.

Finally, there was no vitamin D alone group, as I recall, only a vitamin D + calcium group, a calcium group, and a placebo group.

Irrelevant.

# David Gorski on 27 May 2013 at 12:28 pm

Finally, there was no vitamin D alone group, as I recall, only a vitamin D + calcium group, a calcium group, and a placebo group.

Irrelevant.

How so? It’s actually very, very relevant, as is the issue of cancer not being a primary outcome measure of the study. That you don’t understand why these issues are so relevant indicates to me that you don’t understand clinical research very well.

#Nigel Kinbrumon 27 May 2013 at 1:42 pm
David Gorski said…

Finally, there was no vitamin D alone group, as I recall, only a vitamin D + calcium group, a calcium group, and a placebo group.

Irrelevant.

How so? It’s actually very, very relevant, as is the issue of cancer not being a primary outcome measure of the study. That you don’t understand why these issues are so relevant indicates to me that you don’t understand clinical research very well.

1) The RCT used Ca + D. Therefore, the conclusions apply to Ca + D. If they’d wanted to test D alone, they would have. They didn’t. Why don’t you write a letter of complaint to Joan M Lappe about it?

2) Whether the outcome was primary, secondary, tertiary, quaternary or n’ary is irrelevant because the parameter in question (all-cancer diagnoses) was still accurately recorded. That you can’t understand such a simple concept boggles my imagination.

#David Gorski on 27 May 2013 at 2:34 pm

As I’m leaving permanently, what’s the point?

Ah, flouncing off again. It’s probably long overdue. I’ve been getting a few complaints about you here as well. Perhaps you should ask yourself why complaints seem to follow you wherever you go.

“Whether the outcome was primary, secondary, tertiary, quaternary or n’ary is irrelevant because the parameter in question (all-cancer diagnoses) was still accurately recorded. That you can’t understand such a simple concept boggles my imagination.”

I rest my case that you do not understand clinical trial methodology and interpretation. I couldn’t have demonstrated it better myself to anyone who actually does understand clinical trial methodology and interpretation. Thanks!

You sir, are an asshole. I spelled it the American way, just for you!

I rest my case that you're either trolling, or stupid, or both. Whether the outcome is primary, secondary, tertiary, quaternary or n’ary is completely and utterly irrelevant. It always has been and it always will be. You're effectively saying that only the first item in a shopping list should be bought because all of the other items in the shopping list are irrelevant. Bullshit!

Denice Walter May 27, 2013
@ Marc Stevens Is Insane:
I believe that Nigel is like two bright guys I know: they are well educated and professional in fields outside of SBM/ life sciences (business). Thus they read alt med ‘research’ (also see today’s post by Orac) and don’t get how it DOESN’T work in reality. It sounds like nutrients can do all of these wonderful things – that they can’t- at least not in RL. But the woo-meisters don’t tell you that part. We do.

So of course they think that these products are very useful- and they need celtic salt or ground organic flaxseed- as I know all too well.

However, if they’re smart- we can talk to them:
explaining how that *in vitro/ in vivo* thing works.
Or- as I often do- illustrating how much of the so-called science they read ( woo) is actually more accurately called “advertising copy”.

Businessmen seem to grok that.

Denice, seriously? I'm disappointed. I thought that you were one of the few reasonable posters on Gorski's blog and then you go and write that crap?

I do not read "alt med ‘research’", unless you're calling what's on PubMed "alt med ‘research’"? I've been reading studies on PubMed for years, so I know about the use of shoddy methodology to fudge results. The Lappe study doesn't use shoddy methodology. It's a Randomised Controlled Trial using double-blinded placebos and randomly-selected subjects who were post-menopausal women. Try to pick holes in it.

flip May 29, 2013
Hmmm… it occurs to me I probably haven’t been that overt about one other thing:

Lilady, I am sorry that you were called those things, and I certainly don’t think you should have been called names. I do think Nigel was wrong and do think he should be called out for it.

And I’m sorry for not making that clearer before.

flip, I'm not going to question your intelligence. However, why you're apologising to lilady boggles the imagination. lilady is a despicable human being. She pushed me to the point where I called her rude names, names that were not misogynist and for which I apologised. I explained about "twat" on SBM. I even posted a link to Wiktionary! You don't read things thoroughly before commenting.

Marc Stephens Is Insane May 31, 2013
Oooooh, Nigeepoo is ANGRY! He’s pulled a DJT, posting a “rebuttal” to all the comments here and on SBM. I’m suprised it’s taken him this long.

He’s calling Orac an a**hole and stupid, among other things. He’s invited us all to comment on his blog because he has an “open moderation policy” and “allows all comments.”

http://nigeepoo.blogspot.com.au/

I see that you idiots on RI are still reading my blog. I'm not the slightest bit angry, so you can give the projection crap a rest. For the record, most of you come across as assholes. You can't even quote me correctly. I said that I have fairly lax moderation criteria. Do try to get something right, for once in your miserable lives.

Anyway, you lot are now boring me with your never-ending inability to discuss things either accurately or rationally, so I'm not going to bother polluting my blog with any more of your crap.

P.S. I still occasionally read the comments on Gorski's blogs, so for the benefit of you peeps who read mine:-
1) "Black-list" means exactly what it says. It means that you're banned from posting comments.
2) The Lappe et al 2007 study was a good study. Just because some Messiah-like person says that it's a bad study and applies false reasoning to back himself up, doesn't make him right and me wrong. As I've previously pointed out, surgery's not exactly rocket science is it? I designed complicated electronic communications systems for 29 years. Just saying! ;-) Denice, I've got nothing against you. You've just been drinking Gorski's Kool-Aid for way too long. That's not a euphemism, by the way! :-D

Look what I just found. Exposing Dr. David H. Gorski, M.D., Ph.D. who believes he can use a cloak of anonymity and character assaults to discredit opposing views. Sorry Doc, but your game is up.

He's not the Messiah. He's a very naughty boy! :-D

\ curves and U curves: Vitamins D3 and K2 again.

Here are some curves relating to Vitamin D. Ref: http://www.ncbi.nlm.nih.gov/pubmed/23601272

Hazard Ratios (HRs) vs serum Vitamin D level

The solid lines are the 95% confidence intervals (CI) & mean for all-cause mortality. 95% CI's are the values within which 95% of the subjects tested fall. 2.5% fall below the lower CI and 2.5% fall above the upper CI. The dashed lines are the 95% CIs & mean for coronary heart disease (CHD) mortality. Most of the curves follow a \ curve, indicating that more Vitamin D is better, up to 66ng/mL (150nmol/L, the level that I'm at). The interesting curve is the upper dashed line, which follows a U curve.

The U curve indicates that a Vitamin D level of greater than 30ng/mL (75nmol/L) increases the Hazard Ratio (HR) for CHD in the top 2.5% of subjects only, relative to 30ng/mL, even though the mean HRs for CHD & all-cause mortality (the more important parameter) are decreasing, up to 66ng/mL. What's occurring?

See Vitamin K. The increase in HR for CHD mortality above 30ng/mL in the top 2.5% of subjects only is probably due to calcification within artery walls, due to under-carboxylation of osteocalcin in bone Matrix Gla Proteins, caused by insufficient Vitamin K2 rather than excessive Vitamin D. This is why I supplement with ~1mg/day of Vitamin K2. See also Vitamin D toxicity redefined: vitamin K and the molecular mechanism.

Vitamin D, cancer, cliques and flouncing.

First Google Image Search result for Vitamin D, cancer, cliques and flouncing.

This is a continuation of my previous post Enzyme kinetics, standing on the sun and weird blog comments sections.

Apparently, I didn't like the answers that I received on the blog in my previous post, so I flounced. The study that I asked for opinion on was Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. If I showed you an RCT where deaths from all cancers fell by 77%, what would be your reaction? My reaction would be "That looks promising. More work is needed to investigate it". One person (sophia8) reacted thusly. Other reactions that I received (with their logical fallacies) were as follows:-

Pure coincidence. Argumentum ad ignorantiam.

More than 1,100iu/day of Vitamin D is harmful. Straw man. I didn't say that people should take more than 1,100iu/day of Vitamin D (even though I take 5,000iu/day, which isn't harmful). Also, argumentum ad ignorantiam. See enzyme kinetics in the previous post.

You're cranky. Ignoratio Elenchi.

The study wasn't testing Vitamin D on its own. Straw man. I didn't say that it did.

By the way, “Nigeepoo”, taking supplemental vitamin D is not a proven way to prevent sunburn and is not an adequate method of protection from getting skin cancer (despite assertions in your blog). Straw man for the first part of the sentence. I didn't say that it was. Argumentum ad ignorantiam for the last part of the sentence.

Going for long drives with the top down and broiling gently without sunscreen on a repeated basis is dumb. Straw man. I didn't say that I did. I obviously don't go for long drives with the top down in the middle of the day on a sunny Summer's day. That is dumb. Like, duh!

I'm curious why you found my response to be satisfactory but lilady’s to be unsatisfactory. Could you explain? Ignoratio Elenchi.

Did I mention all of the mis-quoting?... Oy!

Maybe they should have done a bit of basic research, like:-

Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: Recommendations for clinical practice.

The effect of calcium and vitamin D supplementation on obesity in postmenopausal women: secondary analysis for a large-scale, placebo controlled, double-blind, 4-year longitudinal clinical trial.

Vitamin D, cardiovascular disease and mortality.

Why randomized controlled trials of calcium and vitamin D sometimes fail. Essential reading.

I'm the sort of person who's not interested in cliques or secret societies. I'm therefore not interested in joining a cliquey, ivory-towery blog where you have to conform to a set of unwritten "rules" to be accepted, some of which are eccentric (Question: Which blogs insist on the use of manually-typed blockquote tags? Answer: Only that one). I decided to leave. I even apologised to some commenters for my language in some of the arguments.

I wondered why that blog and its owner annoyed me so much. Then it hit me (like a lost boomerang)!

Hmmm. See Brain Surgeon meets Rocket Scientist ;-)

Other comments:-

Orac
May 19, 2013
Nigel, you need to tone it down, too.
I’ve warned both of you once already. This is the second warning. There won’t be a third. To show you I mean business this time, your comments are going into automatic moderation. You two have already wasted more of my time than you’re worth.

Which part of "Can people please stop leaving comments aimed at me, unless it’s an acknowledgement. I don’t want to have to leave any more comments on here – ever." did you not understand?

MI Dawn
May 19, 2013
@Nigel: we responded to the Lappe information. It didn’t prove what you say it proved. Now, if you do have something to say, give the peer-reviewed proof.

Straw man. I didn't say that it proved anything.
Which part of "Can people please stop leaving comments aimed at me, unless it’s an acknowledgement. I don’t want to have to leave any more comments on here – ever." did you not understand?

lilady
May 19, 2013
Thank you Orac for your intervention.
The bottom line for Nigel and Lisa is that they, by their vicious unwarranted personal attacks, have drawn unfavorable publicity to themselves and their blogs.

There's no such thing as unfavorable (sic) publicity for my blog, as far as I'm concerned. What you have done, by your vicious, unwarranted, lying and malicious defamatory personal attacks on me, is to draw unfavourable interest from me.

flip
In a place where no federal police turned up today
May 20, 2013
What a pity they both seem to have flounced off without bothering to respond to the questions put to them. I am not surprised though.

Which part of "Can people please stop leaving comments aimed at me, unless it’s an acknowledgement. I don’t want to have to leave any more comments on here – ever." did you not understand?

Estimated macronutrient and fatty acid intakes from an East African Paleolithic diet

Thanks to Stephan Guyenet for bringing the study n-6 Fatty acid-specific and mixed polyunsaturate dietary interventions have different effects on CHD risk: a meta-analysis of randomised controlled trials to my attention in his post Diet-Heart Controlled Trials: a New Literature Review. This shows that diets high in omega-6 (n-6) polyunsaturates but low in omega-3 (n-3) polyunsaturates are heart-unhealthy.

In the West, we are advised to eat lots of "heart-healthy" sunflower oil & spreads. These contain about 70 times more omega-6 than omega-3. Safflower, Grapeseed, Corn & Groundnut Oils also have high omega-6:omega-3 ratios, according to Comparison of Dietary Fats Chart.

I then found the following study also on the British Journal of Nutrition:- Estimated macronutrient and fatty acid intakes from an East African Paleolithic diet.

This shows that traditional hunter-gatherer diets have a short-chain omega-3:omega-6 ratio of 1·12–1·64 and a long-chain omega-3:omega-6 ratio of 0·84–1·92. In other words, there is a moderate balance between omega-6 and omega-3 polyunsaturates.

The diets are also relatively high in protein (25–29% energy) and fat (30–39% energy) but moderate in carbohydrate (39–40% energy).

I thought that followers of a Paleo-type diet would find this interesting.

EDIT: I've just noticed that O Primitivo has already posted about this study!

Things that make you go pink.

Strenuous exercise. Alcohol. High-dose Niacin. All of these things make you go pink. All of these things are also good for your heart & circulation. As I mentioned in Red, red wine and very sharp pointy things, one glass of red wine significantly lowered my blood pressure in less than 10 minutes, probably by making my arteries dilate (which made me go pink) and by reducing my mental stress which lowered my stress hormone levels.

According to JBS2 guidelines (which I don't fully agree with), CVD risk factor increases with increasing blood pressure. It also increases with increasing TC:HDL ratio. What increases HDL? Things that make you go pink. What we now need is a study showing the effects of blushing on the risk factors for CVD!

Vitamin K

After Vitamin D, Vitamin K will be the "next big thing" you hear about in the media. Why? Just Google "Vitamin K" and see what comes up. At the top of the list is good ol' Wikipedia.

Vitamin K used to be thought of as only the blood clotting vitamin. Some new-borns have to be given Vitamin K injections to ensure proper clotting. However, Vitamin K is needed for the carboxylation of osteocalcin in Bone Matrix Gla Proteins. The what of what in what? In simple terms, Vitamin K is needed to ensure that dietary calcium goes into your bones, rather than into your artery walls, kidneys, brain etc. A lack of Vitamin K can cause osteoporosis. To prevent/treat osteoporosis, either Vitamin K1 (phylloquinone) or Vitamin K2 (menaquinone or menatetrenone) will do. I used 15mg/day K2 (plus Calcium plus Magnesium plus Vitamin D3) to reverse osteoporosis (bone density -2SD) in my lumbar spine.

However, only Vitamin K2 is effective at removing calcium from the media of artery walls. In The Rotterdam Study, "The relative risk (RR) of CHD mortality was reduced in the upper tertile of dietary menaquinone (K2) compared to the lower tertile (RR 0.43, 95% CI: 0.24, 0.77). Phylloquinone (K1) intake was not related to any of the outcomes." An RR of 0.43 means, on average, a 57% reduction in heart attack deaths. I've now put K2 in Cholesterol & Coronary Heart Disease.

Vitamin K2 is required for brain health. See Look after your brain.

See also Vitamin K₂ prevents hyperglycemia and cancellous osteopenia in rats with streptozotocin-induced type 1 diabetes and Vitamins D and K as Pleiotropic Nutrients.

Good food sources of Vitamin K2 can be found here.

Warfarin antagonises Vitamin K, so it can result in arterial calcification. Anyone taking warfarin should ask their GP for regular check-ups to keep an eye on this potential problem.