What do you consider to be ideal cholesterol readings? I am about to visit a new doctor, a D.O., and I am sure she is going to insist on blood tests for cholesterol plus stress testing, etc. My thyroid TSH was 2.70, but she is already showing reluctance to prescribe any thyroid meds. It is going to be a battle.

And it is not just about the wheat either.  It’s all carbs.  Fructose, oats, rice, pasta, potatoes and certain fruits, etc. all drive up HbA1c and small LDL.  Just for a reality check I bought a can of and made a bowl of “properly prepared” Scottish oatmeal yesterday according to Nourishing Traditions.  Those are the minimally processed chewy steel cut oats soaked with warm water and kefir overnight and served with butter and cream.  Yeah, they were good alright, but my fasting BG was 88 and one-hour PP was 158.  A fast 5-mile run and it was back down to 84.  The container is in the garbage can now.  This morning was two pasture raised eggs and bacon with ½ cup of blueberries and Greek yogurt.  Fasting BG 89 and one-hour PP was 88.  My HbA1c went from 5.8 to 5.1 in less than a year and hope to get below 5.0 soon.  The stubborn small LDL percentage dropped during same time period but still have a way to go in that regard.

I'm not completely sold on HbA1C < 6.0% being a useful metric for anything but populations.  The problem is that the current HbA1C tests do not control for erythrocyte age and I see wide variations among piers on simialr  grain free lowish carb healthy diets.

There has been much more research on this effect as it pertains to diabetics that have falsely low HbA1c:  http://www.ncbi.nlm.nih.gov/pubmed/9773739
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2581997/

There is some evidence out there that it works the other way as well, and it makes intuitive sense that the lower inflammation and oxidation associated  with a healthy diet would increase erythrocyte longevity.

Of course observational studies about any topic (small LDL or HbA1c) are always to be taken with a grain of salt.

I wonder if you have ever experienced with any of you patients  what is going on with my husband?  He has very few small LDL particles, at least according to a VAP test - he is type A with lots of large, fluffy LDL.  But his HbA1c is 6.1.  His fasting glucose is 80, 1 hour post-prandial it's 1685, triglycerides are 60.  This is all on a grain-free, very low-carb Paleo diet.  Do you have any clue what is causing the HbA1c to be elevated?  Could it be anything besides carbs?  He gets lots of exercise and is very fit and lean.  

Some have suggested that too much protein can also cause elevated HbA1c, due to gluconeogenisis causing higher levels of glucose.  But why would the body make more glucose than it needs?  And why would that excess glucose not show up in his fasting and post-prandial glucose numbers?

Is there any other factor, besides blood glucose, that can contribute to elevated HbA1c?  No doctor yet has been able to answer this question for us.

Sorry for the typo, his 1 hour post-prandial glucose is 85.

The most common explanation, Rosanne, is that the HbA1c can stay high long after blood sugars have come under control.

It may be due to the extended longevity of RBCs that occurs in the setting of low-carbohydrate diets that allow a previously high HbA1c to stay high for an extended period.

There's also the possibility of a hemoglobin variant that allows this.

I would put more stock in the blood glucose values by fingerstick than the HbA1c.

Thank you for explaining this.  I just had my blood work done for the first time since quitting wheat and going low carb in April.  Since I've lost a lot of weight, and a lot on my waist, I am very curious to see what my numbers are.  This will help me compare the important stats.  What is an ideal HbA1c?

I can't go near oatmeal, steel cut or any other type.  Its just eggs and avocados for breakfast these days with a lot of Asparagus in the spring with my yolks.  Oatmeal has been banished for good.

Your article discuses how the combination of small LDL particles  and high blood sugar
results in plaque. Is the article cited below  by University of Washington at St. Louis useful here? The article points out the role of low Vitamin D in plaque formation with LDL  and high blood sugar. Or am I confusing two separate mechanisms in plaque formation.

http://news.wustl.edu/news/Pages/14489.aspx

Hi, Bob--

Yes, I believe it is two unrelated mechanisms. However, this is a fascinating finding to tell us why people do so well from a heart standpoint when we correct vitamin D deficiency.

Smart move, Pj!

Hi, Arlene--

We aim for 5.0% or less.

Thank you for explaining the topic. i learn more about Small LDL. great post.

Dr. D,  
Can this be related to the lysine- arginine balance in the body? Would taking arginine supplements affect the amount of lysine residue causing problems in any way?  Just thinking out loud ...

Thanks!

Jeanne

HI Doctor Davis,

I know its not the right place, but I could not find your email.

I read "wheat belly", it was revolutionary for me,  and I am persuaded it can bring much relieve to many ailments.

I also wrote several posts about this issue on my health blog (in Hebrew)  based on your book and your Blog.

Thank you for the great service you are offering in your work!

Amit.
Israel.

Hello Dr. Davis,
I'm new to your blog. Just finished reading Wheat Belly. Excellent book! I also listened to the podcast with Robb Wolf. That's how I heard about you. Not to get off topic (didn't know how else to contact you) and this is probably a silly question, but would like clarification if you could help. I've been purchasing the 85% Lindt chocolate bars until you mentioned that you eat the 90%. I read the label and it said that it is pressed with alkali. You mentioned to avoid this process as it removes the healthful flavonoids. By saying "pressed" is that a different process? The chocolate was very good, but I want to make sure I'm getting the healthful flavonoids, especially when we don't eat too many sweets. Thank you so much for your time.

Hi Dr.,
I am confused how to  reconcile  HbA1c details  from J Am Coll Nutrition 2005, Vol.24(1):22-29
"Dietary Carbohydrate and Glycated Protein in the Blood in Non-Diabetic Subjects"
http://www.jacn.org/content/24/1/22.full
(and their relevant references no. 10 -  19 & 34-39 )

This has been going on for 2 1/2 years and in fact, the longer he has been low-carb Paleo, the higher the HbA1c has gotten.  When he started, it was 5.5 and has slowly
crept up to the 6.1 reading.
Thanks for the mention of the hemoglobin variant, I guess that's must be it.  Can we stop worrying about the HbA1c since his glucose values are so good?

Dr. Davis:
What do you you think of Jenny Ruhl's advocacy of the 5% club at Blood Sugar 101? Your guidelines appear to be more aligned with Dr. Bernstein's and Dr. Ron Rosedale's? Do you think that all individuals ( including prediabetics, daibetics and glucose intolerant ) should strive for a HbA1c below 5%?

HI, STG--

That is precisely what I aim for, also: HbA1c of 5.0% or less. At that level, metabolic consequences of blood sugar essentially disappear. This is, of course, at variance with conventional guidelines.

That would be my vote. Ask your doctor, also, about fructosamine, another sugar markers.

Hi, Might--

Were you referring to their conclusion about polyunsaturates?

My bar says "processed" so, yes, the flavonoid content can be expected to be reduced in this bar. The best way to get a full dose of cocoa flavonoids is in undutched cocoa powder.

I still think you can enjoy your dark chocolate, but you just might not expect full benefit from this particular bar.

Thank you, Amit!

What is the wheat situation in Israel? Is it pushed there as much as it is here by official agencies and food companies?

Sorry, Jeanne, I don't believe the answer is known.

Hi Dr. D.,
Authors in this report say glycated protein & HbA1c do not interact  with blood glucose in same way (ref #17) and that it is glycated albumen rather than glycated hemoglobin that is very senstitve to blood glucose levels (ref # 18,19); especially since 60% HgA1c is genetic (ref #61).
AGE (advance glycation endproducts) they say is more indicated by fructosamine level from high blood glucose. Although diabetics with high fructosamine also have high HbA1c. whereas for a non-diabetic  high fructosamine does not relate to their HbA1c level (ref#16).
This impies that (since most obese individuals never will become diabetic &  longevity/cognitive function of the overweight is good) a lot of the risk factor of small LDL with HbA1c depends on genetics/ epigenetics.
My confusion is if your insistence on HbA1c for non-diabetics is misdirected or just due to it being a common first test people can do.

Wheat is the most common carbohydrate in Israel. It is eaten almost every meal. I think that the largest source of calories is wheat.

Regarding Diabetes there is no awareness that whole wheat is especially bad for such patients. Diabetes association (and many more) do recommend whole wheat. Although they are suggesting to avoid eating large quantity of bread at once.

Wheat is being pushed, though, I don't think that somebody here is pushing wheat deliberately, just coping recommendation from abroad, and using the most cheap and easy carbohydrate.

Amit.

I have been on my Wheat Bellies journey for 8  weeks now.  I am trying to follow your suggestions on heart health and I know that you have your plate full right now, but just a request.  Have you ever thought of doing healthy heart retreats?  I would love to have a chance to go away for a long weekend, have all my blood work done right, have it evaluated, talk to a doctor and then maybe have a few cooking classes.  Throw in a few yoga classes or walks for stress reduction and you have a whole picture!!  

I have high blood pressure that is 'controlled' to some degree with Tekturna (150mg) and Amlodipine (10mg). This morning it was 150/90, so it is often not very controlled. Since 9/1 and going wheat free, I have lost 23 pounds but still have 50 to lose.  My take away from your writings is that plaque is the  main cause of heart disease and that keeping a low blood glucose level is the best strategy, but there is not much about  high blood pressure in your work.  What role does it play and will being a wheat free low carber offer me relief from my high blood pressure?  Or will it stay high since I have a family history of high blood pressure and therefore will probably have to continue on my meds.  While I, of course, am doing everything in my power to lower my blood pressure, is it not really a number I should focus on when trying to control my heart health?

Hi Doc,
have you seen this? You are prominently featured here:
http://www.lef.org/news/LefDailyNews.htm?NewsID=11842&Section=Nutrition
Great summary!

Are you going to translate his books into Spanish some day?
I'm very interested in reading them. thanks

Hi, Marta--

There has been interest specifically in Wheat Belly for translations. Spanish is at the top of the list.

When that happens, I will announce here and elsewhere. Thanks for asking.

Thanks, Renfrew!

Life Extension has been an important supporter of my efforts and vice versa.

Hi, Nora--

Excellent suggestion on the heart health retreats. I've thought a lot about it and will likely do it in future. Just not quite sure about the details. One hurdle: Few people want to fly to Milwaukee, so we'd have to find an exotic or interesting, probably warm, place to do it.

Hypertension is indeed a big issue. It is also among the last things to respond to weight loss and diet, often lagging behind many months after weight loss. So it really pays to be patient while you are on this health journey. Given your family history, you still might be left with hypertension, but at least you will have minimized it.

Thanks, Amit.

By the way, all anyone has to do is check a fingerstick blood sugar 1-hour after consuming anything wheat to observe the astounding blood sugar consequences of wheat consumption.

Hmmm. I'm sorry if I'm being dense, Might, but I'm still not sure I follow.

I'm not actually advocating anything except to show how glycated small LDL is a really bad player. When viewed from multiple different directions, small LDL particles are looking worse and worse. In this instance, having any measure of glycation phenomena, whether fructosamine, glycated albumin, or glycated hemoglobin, suggests that small LDL particles are also being glycated and thereby gaining heightened atherogenic potential.

Dear Dr. Davis,

I am reading your book Wheat Belly and want to thank you so much for writing this book.

I've avoided gluten for years.  Arthritis and other annoying symptoms vanished...but I started gaining weight!   My blood sugar starting rising!   I couldn't understand it!  It was horrifying!  Well thanks to you, I realize that gluten free breads, candies, flours,  frozen pizzas, pastas and those gluten free "tv dinners" sold at Whole Foods did nothing to help my waist line or blood sugar.  I am now following the wonderfully easy plan in your book and am confident the weight will come off.

Thank you for such terrific recipes.  Will you be writing an accompanying Wheat Belly cookbook as well?  I certainly hope so.  Please do!   If not, can you recommend some cookbooks that comply with your eating instructions?

Thanks again for such a life changing book.  Sally

There are a few people in Israel trying to enlighten others about the dangers of wheat and other 'modern' carbs.  My sister is one of them, has been trying to think of ways to get some essays to the public.  But what Amit says is correct - a lot of wheat is eaten there, many people buy small breads  rolls daily - it's very fresh, delicious, so it will be a tough thing to stop. Many of the best restaurants in Israel serve Arabic food which always comes with freshly baked loaves of pita.  The 'national snack' is pita stuffed with falafel (fried balls of ground chickpeas, onions, garlic and spices), fresh & pickled vegetablesj, hummus and/or tehina sauce. This is available everywhere and always fresh.  Becasue the food is generally very good in Israel and also very fresh it's hard to avoid wheat, which I've noticed every time I visit.

Dr. Davis, the evidence speaks for itself that consumption of carbohydrates, increase small LDL, suggesting an LC diet of less than 50 grams to mitigate the damage.
But what about endurance athletes (runners, cyclists, triathletes etc.) that work out one and a half to three hours per day and consume copious amounts of carbohydrate to fuel their long workouts.
Is the exercise neutralizing the carbohydrates' harmful effects? If so, can you suggest a dosage for certain amount of exercise?

Hi Dr. Davis,
Non-diabetics just seem to have one feature going for them - their platelets don't respond the same as diabetics. I am inclined to think that albumin in our blood is more relevant than the hemoglobin being glycated . (This is not to criticize your preventative approach , since Type II diabetes can go on to develop &  I like what you are teaching us about small LDL.)

" One common qualitative change in plasma albumin is nonenzymatic glycosylation, which occurs during states of prolonged hyperglycemia....Platelet aggregation ...is enhanced in the presence of albumin that has been incubated in a medium containing levels of glucose that are higher than would be seen in normal patients but are consistent with those seen in diabetics....(Journal of Parenteral and Enteral Nutrition 18:516-520, 1994)

Once the glycation of albumin fosters more platelet aggregation in diabetics (& the insulin resistant person!) their platelets show more secretion and adhesion leading to the vascular plaque build up that the insidious small LDL can get into. Yet, for the non-diabetic the +/- 570 insulin receptors on each platelet normally respond differently to their insulin exposure.

Specifically (in non-diabetics) the insulin actually stymies the platelet from becoming "activated" and probably explains how it is that not everyone who eats carbohydrates suffers cardio-vascular insults. Of course there are non-diabetics with genetic variants that adversely affect their plaque dynamics (ex: defect in insulin receptor signalling, that receptor's Beta subunit, G-protein pathways).

( For the techno-nerds: proper insulin receptor response on platelet keeps  platelet cAMP level from dropping & so no endoplasmic reticulum calcium floods out into platelet cell cytosol, platelet granule doesn't secrete ATP, platelet alpha-granule doesn't secrete P-selectin & there isn't mitogen-activated signalling to make thromboxane A2 , etc.  Basically, in the diabetic/insulin resistant these processes go forward uninhibited by normal insulin signalling & their circulating platelets don't keep rolling along suspended in the bloodstream .)

Omega 3 Fish Oil BAD NEWS for Apoe 4/3!!!  

Ok Dr. Davis, I really need your advice on this one.   In following TYP, I have been taking 3200 mg day EPA/DHA fish oil 1.4:1 ratio.   Recent testing shows I have gotten my HS Omega 3 Index to 9.5,  and my Omega 6 to Omega 3 ratio to 2:9  so this pretty good.   Now for the bad news....ever since I started taking 3200 mg day fish oil...over a 2 month period my HDL went from 48 to 38, a whopping 20% reduction in the critically important good HDL that I need to remove plaque.  I exercise extensively, and I also take 10mg day crestor (crestor is one of the few statins that's supposed to raise HDL not lower it). Now,  I have heard from several sources that Fish Oil (more than 1000 mg day) supplements are actually BAD for Apoe4/3 people because it lowers HDL.  So now I am confused Dr. Davis.....do I follow your TYP advise and stay on 3200 mg day fish oil in order to keep a close to 10 HS Omega 3 Index....but suffer lower HDL and less plaque removal/reversal....or do I stop the Fish oil in order to raise my HDL  but suffer the risks of little to no fish oil??

Please advise...

An extremely confused Apoe 4/3

Hi Adam,
HDL drop can be due to accelerated small HDL's  breakdown/clearance & if that was mostly lingering small HDL then it didn't have much reverse cholesterol transport function left in it anyway. If total HDL drops but small HDL turnover is  now more optimal &/or if it is a greater % of the large HDL then there is better reverse cholesterol transport dynamic despite the total HDL drop.

ApoE has 299 distinct amino acid positions & the difference between the 3 types are due to which amino acid is in positions 112 & 158 ( respectively ApoE4 @112=arginine & @158 =arginine, ApoE3 @112=cysteine & @158=arginine, ApoE2 @112=cysteine & @158=cysteine). Because ApoE4 has arginine at position 112 this then orientates facing away from the standard grouping of 4 helix at that N-terminal to more closely cozy up to the alpha-helix of the C-terminal that in ApoE naturally overlays the N-terminal. Thus ApoE4 can uniquely feature a "salt bridge" to that C-terminal that affects how ApoE unfolds/functions when ApoE goes to work.
ApoE's manner of unfolding at it's N-terminal  is crucial to how it deals with lipids, phospholipids (ex: cell membranes)and  proteoglycans on a cell surface. Fish oil alters cell membrane phospholipid composition and then the proteoglycans there must suitably interact with that EPA enriched type of cell surface. Since each ApoE's C-terminal presents an interface that challenges  how that ApoE  works at any target cell the  peculiar ApoE4 "salt bridge" uniquely conditions the way interactions play out. (And each of the separate 3 classic types of ApoE  can get mutations, mostly at positions 136-150, to complicate degree of LDL receptor interaction, etc.)

Dear Doctor Davis,

I am wondering if you can clarify the "oxidized LDL Cholesterol" concept.  Including, of course the Small LDL as well.

I began wondering if the oxidation is primarily in the package, the LDL wrap, the signaling protein, or the internal body of cholesterol itself. Of course, all of the above is also a possibility.

The nature of the oxidation could be a good clue as to how it is especially detrimental to health, and so far, I haven't found much easily available on the mechanisms of the detrimental effects. While it is useful to know the harmful nature of oxidized small LDL, some insight into the mechanism of harmful effects would be welcome and minimize the nagging question of "Why" for me.

This might be of interest:

A large study called the STRRIDE trial looked at the effects of different intensities and volumes of exercise on LDL particle size in sedentary, overweight men and women over eight months [3].  Group A performed 176 minutes of low intensity exercise (walking) per week.  Group B performed 117 minutes per week at a moderate to high intensity (jogging, cycling, or using an elliptical machine).  Group C exercised about the same amount of weekly time as group A, but at the same intensity as group B.  

As one would likely guess, group C showed the biggest improvement in changing LDLs from small and dense to large and buoyant.  However, a more telling sign was that group B had a stronger effect than group A, despite exercising an hour less per week.  In other words, intensity is more important for improving LDL particle size than volume of exercise.

A follow-up of the subjects in this study showed some discouraging and encouraging effects on the particle size changes [4].  The discouraging news was that five days of inactivity following the study almost completely attenuated the particle size benefits from the trial.  However, before you start labeling exercise as futile, consider this: while five days of rest basically brought the exercise groups back to baseline LDL particle sizes, they were still much better off than the sedentary control group, who experienced significant digressions in particle size during the course of this study

Hi James Buch,
The enzyme hepatic lipase's (HL) lipolytic hydrolysis of the phospho-lipids on the LDL surface changes it so that LDL's load of cholesterol esters can get taken out; this reduces the molecule's volume and thus is then small LDL (smLDL). Men have more HL than women, until they go through  menopause, and this propensity toward smLDL ( that can get oxidized) may explain male's earlier tendency of coronary artery disease. Visceral/central obesity trends to upregulate HL & it seems visceral obesity affects men more than women (of course central obesity in both women & men will raise both  genders'  HL enzyme levels). What decreases HL levels are things like calorie restriction & aerobic exercise (sedentary life increases HL).

Doc harps on avoiding elevated triglycerides after meals that load triglycerides into VLDL  molecules because the enzyme cholesterol ester transfer proetein (CETP) shunts triglycerides from VLDL (& chylomicrons) over to the standard circulating "big bouyant" (large & fluffy) LDL and fosters transfer of cholesterol out of that LDL; the triglyceride takes up less space and thus get smLDL.
Central obesity usually correlates with elevated triglycerides and increased HL levels. However, if triglyceride genetics (or epigentics from Doc's diet ,etc.)  in the obese without that usual accompanying high triglycerides then that upregulated HL doesn't cause a lot of that individual's standard "big bouyant" LDL to become smLDL. HL also hydrolysizes triglycerides (and phospho-lipids) of chylomicrons, BetaVLDL, IDL, LDL & HDL. Both CETP & HL enzymes being elevated alone, or together, can provoke smLDL - genetic polymorphisms exist for both enzymes.

sm LDL has less antioxidants left yet it's surface has higher ratio of poly-unsaturated acids which make it's phospho-lipids more at risk of oxidation. And smLDL has less sialic acid left on it's surface which fosters more poly-anion proteoglycan binding that increases the smLDL molecule's transportability across the endothelial lining into the artery wall .
Doc harps on need for Magnesium because in real time magnesium is what interrupts the oxidation of smLDL from locking into an altered state & then salvaged plain old smLDL doesn't get to go on to be so damaging.

Continued for J. Buch,
Oxidized small LDL (oxLDL)  has fragments from it's oxidized PUFA (poly-unsaturated fatty acid) that are reactive aldehydes (ex: malon-di-aldehyde & 4-hydroxynoneal-lysine) which then fragment that smLDL's  lipoprotein ApoB.  That peroxidation of a PUFA acyl chain of  the smLDL phospholipid  leaves a type of carboxyl portion that the beta-2-glyco-protein I (Apo H) binds to using a "reactive" ketone as ligand link. Thus it is the position of the "reactive" ketone (keto-cholesteryl-9-carboxy-nonanoate) on the involved cholesterol molecule's spine that determines the % of glyco-protein bonding that occurs (genetics influences ketone placement on a human cholesterol molecule).

Magnesium (Mg++) in the very early stage of glycated protein (Doc warns against advanced glycation end products) hooking up with LDL reverses the glyco-protein link to the "reactive" ketone. But if deficient Mg allows time to consolidate that contact then only a physiologiclly abnormally high pH will let Mg re-break that bonding.

Immunological T cells respond (with age & gender differences)  to try to get oxLDL off the artery wall;  and, if there is too much to handle there is the risk of developing a so-called oxidized LDL-containing Immune Complex (oxLDL-IC). And this oxLDL-IC provokes cytokines that perpetuate the inflammation response. Over time and older age there is  less output of a malon-di-aldehyde oxLDL  immune response; which is possibly what leads to long established plaque having less lipid component and more involvement of collagen. It is relatively younger plaque that is unstable and more likely to rupture; the collagen draws in more Calcium and unfortunately provokes artery hardening problems.

Now the lipid part from this oxLDL-IC gets into an immunological monocyte cell's endosome  and the ApoB gets into that same monocytes lysosome - sub-compartments inside the cytosol (cell interior). Then the lipid part in the endosome triggers heat shock protein (HSP 70/70B) which wrenches things so that the lysosome can't get to work on the lipid and ApoB prevents the lysosome from doing proper interactions at the inside of that cell's membrane to expel  the burdens. Once oxLDL cholesterol esters bulk  up a macrophage (monocyte) due to increasingly futile lysosome  activity  it becomes the notorious "foam" cell. Eventually that macrophage cell dies and the whole load get's polymerized into plaque.

Hi Dr. Davis - with your indulgence:
Back to platelets( see above Nov. 7): vascular remodeling with age &/or ROS exposes a bit of phosphatidyl serine  that platelets can "snag" onto as platelets flow along. Key to accomplish platelet snagging is signaling by  the promoter P2gamma12 and normally insulin signaling down inhibits P2gamma12. But, notably for Type II diabetics (and assumedly proportional to an individual's insulin resistance) their insulin doesn't inhibit that snag signal. Type II diabetics also have P2gamma12 upregulated in their platelets. And if anyone is of P2gamma12  haplo-type H2 those individuals will have even more of the receptors for it and therefore an  increased risk of peripheral artery disease. Irregardless of haplo-type, the Type II diabetic's propensity for peripheral artery problems are compounded by  their basal level of excess P2gamma12 .

Adhesion to the artery then physically involves the platelet surface Glyco-protein Ib & vonWillebrand factor hitched to collagen provoking Integrin 2beta1 (GPVI) so the platelet/collagen sets in place. If the level of promoter P2gamma12 in that challenged site is fortuitously low then the rate of adhesion to the blood vessel is poor. So, predictably, for Type II diabetics the adhesion rate (like platelet secretion & aggregation) is higher than normal. GPVI insult also signals a release of ADP & this ADP (like collagen itself) independently induces aggregation of platelets; the plaque recruits to build itself up to be more fibrous. The plaque matrix serves as nesting for oxLDL & dying macrophage foam cells to polymerize with.

ROS remodeling agents of the vasculature come from mitochondrial activity and  it appears certain (overlooked) relevant gene pheno-types (and their respective polymorphisms) can be pro-plaque (or preventative) - speaking here in the sense of  a primal influence on plaque risk as well as  tendency of the actual amount of plaque. Sirtuin 5 (Sirt5), a mitochondrial Sirt (there are nuclear Sirt too) binds to Uncoupling Protein 5 (UCP5) and governs that (& other) UCP. Sirt (there are 6 types) remodels chromatin (DNA spooled around a histone ) via histone de-acetylase enzyme; while our UCP (there are 5 types) work in the inner mitochondrial membrane governing the proton electro-chemical gradient that is integral to the chain of oxidative phosphorylation (a way to generate ATP, among other functions).

Sirt action on DNA includes (among other dynamics) the cellular level encoding of how individual fatty acid metabolism fine tunes -  lipid fatty acids included.Sirt action on DNA includes (among other dynamics) the cellular level encoding of how individual fatty acid metabolism fine tunes -  lipid fatty acids included. Doc's diet/protocol may ( I suggest) sometimes  tweak out favorable health response(s) via induced epigenetics, because of remodeling that is induced in the chromation DNA unit packaging . Sirt's histone de-acetylase working depends on NAD- to drive Sirt and Doc's diet/protocol theoretically seems to be capable of altering NAD flow patterns from his weaning of cells'  mitochondria off of glucose.

UCP5  rules the inner mitochondrial membrane potential & the rate of oxygen use, which can become relevant to ROS levels. Both UCP5 and Sirt5 are upregulated in hypertension and Type II diabetics; the confluence of having geneticly more UCP5 along with Sirt5 are implicated in increased carotid artery plaque. (Of course nothing is linear in humans so haplo-type T- carrier UCP5 polymorphism rs5977238 benefit with less plaque risk and reduced plaque numbers.) Note: I am skipping over other Sirt & UCP; but will add that lots of pheno-typic UCP1 spins out extra amounts of reactive super oxide to drive down nitric oxide and implicated in accelerated aging of the vasculature.

Might/Doc - Does this mean that if you DONT have proper insulin receptor response that all of the things listed in the last paragraph become untrue? (meaning bad?)

Would this mean that you are implying a low carb diet would be the best solution due to the insulin issues?

I ask because I cannot raise my HDL for the life of me. It is completely stalled at 40. And my LDL is primarily small dense kind. I have only really had this problem since going "LC Paleo" and adding a ton of sat fat to my diet but then I added back in starches and other carbs and became more moderate carb, while still continuing to eat bacon/eggs/cheese/cream/butter/beef/coconut oil/ghee/nuts etc.

Now I've got people telling me to go back to LC, and exactly the reverse, people telling me that I need to cut out the fats including dairy and go low sat fat.

Mito....:
I have viewed your comments at the Hyperlipid and always appreciate your detailed biochemical/physiological explanations per topic. Your grasp of details and mechanisms is amazing! What is your background? Are you a biochemist by trade?

A retreat is an excellent idea!  It would be a great time of learning and discussions. I vote for Gulf Shores Alabama

HI STG,
My hope here is that I never hijack Dr. Davis'  blog ( I never personally posted on Hyperlipid blog).  I trust  Doc's readers know he is not responsible for any errors I make. Being semi-retired from consulting on agro-industrial projects in developing countries I feed my mind by keeping up with health science & commenting here about correlations to Doc's work.

Hi J. Kronk,
Saw your 11 Nov. query &  feel diet advice here is for Doc to offer (not me). Doc discusses ApoE pheno-types he restricts dietary fat for. You "tagged" me where I  was elaborating on platelets' interaction with insulin & how insulin resistance is a game changer (not sure what confusing).

If one is insulin resistant then the signaling to build-up (anabolism) from insulin is selectively diminished and consequently break-down (catabolism) signals get  into play. Proteo-lysis is protein cleaving and HDL's protein component can be more rapidly subject to proteo-lysis; which I presume (?) is why/how some people degrade their HDL so quickly. Genetic quirks (& gender) also hit HDL levels notably;  yet  if quick enough turnover the "stale" HDL  might be being replaced by more functional HDL. According to the "HATS" study HDL alone is not a predictor of coronary artery disease mortality.

Niacin usually decreases rate of catabolism of HDL,  it helps secrete more ApoA1 to make into HDL & decreases amount of  smLDL. Niacin isn't perfect since it alters the extent to which HL (hepatic lipase enzyme) can work on a  HDL molecule to morph  it into the kind of HDL that has the maximum reverse cholesterol transport capability. HL is what hydrolyses the triglycerides in HDL - so, basicly if HDL loaded with trigs it has sparser room for scavenging cholesterol.


One's genetic response to increased levels of circulating palmitate free fatty acid can interfere with insulin signalling in the liver. Whether clinically insulin resistant or due to a genetic quirk (you?),  palmitate can phosphorylate liver insulin receptors in a manner unlike "normal" individuals do in the Akt process (insulin normally should get Akt going to stop liver gluco-neo-genesis - since insulin has glucose to drive into cells ). Essentially "excess" palmitate, in this example, is causing only a partial phosphorylation of Akt & is how researchers can use very high fat diets to induce experimental diabetes .

I don't hear you being insulin resistant, so address genetics of Protein Phosphatase 2A (PP2A), which  has components involved in it's regulation and is subject to different structure. How PP2A parts interact with distinct parts of the Akt molecule can  impair some interactions,  yet leave other parts of Akt responsive ( to do what Akt  is normally designed to do). Palmitate can raise PP2A levels in the liver by 30%; so basically the more PP2A  around and/or the molecule's genetic tweaks the weaker a key part of  the liver's Akt response is going to be.

Since palmitate  being in the liver does not stop insulin there from fostering more trigs there are still post-prandial trigs going into the VLDL . In other words the liver insulin resistance and rogue genetics can leave the part of Akt that governs lipo-genesis still responsive to insulin. Doc warns us about trig enriched VLDL & chylomicrons promptly driving  smLDL that doesn't degrade & small particle numbers measure high; he is more adamant about post-prandial trigs but genetic high overnight trigs can occur.

I don't think coconut oil acts the same way high animal fat sometimes does on Akt . We internally make palmitate when acetyl-CoA acted on by enzyme acetyl CoA carboxylase  to make malonyl-CoA that fatty acid synthase converts to palmitate. I think most of coconut oil's fatty acids are metabolized before getting into that pathway so maybe coconut oil is worth parsing when genetics or insulin resistance drives up smLDL.

Mito..
Excuse my error about you posting on the Hyperlipid. I guess I have read your posts elsewhere. In any case, your posts are very educational and explain precisely the biochemistry  Thanks for sharing your knowledge!

Hi Dr. Davis,
I’m 47 yrs old. I’ve had migraines since I was a teen and I developed Athsma this past January (hate it). During the process of discovery the drs found I have a 50% blockage in one of the 5, non critical, arteries running along the back of my heart. Scared me, to say the least. I’ve always eaten quite healthfully (for what I knew), am thin @ 6′ 1″/155lbs (was 175lbs in Jan.). Had total cholesterol of 200/LDL of 146/HDL of 50. Drs wanted me to do Lipitor. Researched and said, “No, thanks.” Started exercising 5-6 days/wk (lifting + walk/run), taking red yeast rice, fish oils, fish, no meat, no dairy, no eggs, lots of veggies/fruit, etc., but still eat beans, oats (every AM), occasional wraps. After 6 wks my blood work (VAP) was as follows: LDL=86, HDL=43, VLDL=17, TOT. CHOL=146, Trigycerides=66, Non-HDL (LDL+VLDL)=103.

Seemed GREAT to me! The dr wasn’t impressed. Said my ‘particle size’ was small: LDL1(a)=8.1, LDL2(a)=0, LDL3(b)=39.5, LDL4(b)=24.9. Density Pattern=B.

I’ve continued but don’t know how to elevate my HDL and reduce the particle size/change the pattern to the more favorable ‘A’. Getting down about this. Working hard but, seems like I can’t find answers that work, anywhere! What might you would work in my situation? Also, Is niacin ANDRed Yeast Rice a bad idea?
I’ll hang up and listen. Thank you,
Mark

PS - I left this post on another page, as well.