Fish oil is the snake oil of the 21st century.  Dr. Ornish has it right on that score, and adding the empty calories of any "fat," including fish oil is counterproductive.  There is nothing to be gained health wise from excess fat, which is the primary source of most chronic diseases.  Try your 30% fat calorie diet on a professional athlete and watch his endurance decline.  The nutritional recomendations of the Olympic committee is MAX 10% calories from fat.  Get OFF the program!

I strongly disagree. We use fish oil to correct triglycerides, among other patterns. Triglycerides are raised substantially by an Ornish-like program. In other words, they exert opposite effects.

Attitude--it's half the battle, isn't it? Great post.

He seems to be in denial. I'm sure that he is not following your guidelines, so no improvement in his health will occur.

When I read about Hank I thought "he could be related!"  Many relatives on my mom’s side of the family are similar to him.  They naturally find faults with situations, other people, and are world class deniers.  They are pretty miserable to be around, to me, for any length of time.  

My family is a real contrast in that my father’s side of the family is the opposite from moms.  They are eternal optimists.  They tend to see positives in most things.  

When it was learned that I had a high calcium score on my heart scan, responses received were as expected.   Relatives on mom’s side called to say - "doctors don't know what they are doing", "eat what you want", "those test scores don't mean anything." etc.  Fathers side of the family has been supportive - with my father going so far as to join me on the TYP diet and supplements.  He didn't have to but he wanted to know what it is like to take fish oil, the niacin flush, and to eat like a cave man.    

Almost everyone who is older on mom’s side of the family, died of heart disease, has heart disease or experienced a stroke.  I want to say to them, why not try something different - like the ideas presented in the TYP book?  What has been tried in the past did not work so well, why not be open to new ideas?  But I know what ever I say will go in one ear and out the other.  They know they know and can not be persuaded other wise.  Being grizzled pessimists is in their blood, I believe.  

I'm glad that I take after my father’s personality.

Dr Davis,

I am not a doctor by profession but an engineer. I am really frustrated in trying to get to the bottom of things in the medical field. It is quite vexing when I cant decide if something is a safe practice or not. Would you please help me (and perhaps many other) understand how I can take oil-based Vitamin D without worrying about Vitamin A levels as well? Should I worry about taking Cod Liver Oil based preparations with questionable manufacturing practices which seems to include filtering to remove the Vitamin D and then adding synthetic form at the end?

If you could get into some details, it would be very helpful.

Regards,

Anonymous, you could take fish oil instead of cod liver oil for the omega-3 and take vitamin D as D3 in softgel form.

Vitamin A can be supplemented by providing its precursors like alpha-carotene, astaxanthin, beta-carotene, cryptoxanthin, lutein, lycopene, and zeaxanthin. Supplying precursors will let your body decide how much vitamin A to make out of it. Supplying preformed retinol bypasses the body's control systems.

Cannell et al recommended an D:A ratio of about 6:1 in IU terms ("Cod Liver Oil, Vitamin A Toxicity, Frequent Respiratory Infections, and the Vitamin D Deficiency Epidemic", a commentary piece in Annals of Otology, Rhinology & Laryngology 117(11):864-870, on page 866, third paragraph).

Maybe it's best to avoid retinol and make sure you get enough A precursors.

StephenB

The yam based forms of Estrogen have a much better safety profile than the others on the market. In fact,the worst reaction I've ever had to a hormone was to a supposedly "bioidentical" estrogens from a compounding pharmacy.

The problem with anabolic steroids apply to bioidentical testosterone supplements too. Too much testosterone is bad for your body.

Does this mean that Benecol is not good to use in lowering cholesterol?

The bit that I find most disturbing in this post is the bit on sterols. Many authorities advise us to use phytosterols or stanols to lower cholesterol. I did find one article on PubMed a while ago (but can't refind it now) suggesting that, since the structure of phytosterols is similar to cholesterol, using them to replace cholesterol shouldn't just be assumed to be a safe thing to do. Do you have any more data or links on this issue?

I came across this post by Dr Michael Holick whom I respect, and naturally all readers here respect your findings from the front line in Milwaukee. There appear to be some differences in interpretation.
*********
Vitamin D2 vs. D3
Vitamindhealth.org
Posted by mfholick on November 27, 2008 under Vitamin D |  
**********
Vitamin D2 and Vitamin D3 Are They Equally Potent?

During the past several years, there have been two studies Trang et al, (Am J Clin Nutr 68:854-858, 1998); and Armas et al, (J Clin Endocrinol Metab 89:5387-91; 2004) that have raised questions about whether vitamin D2, which is found in some supplements, used in some fortified foods and is the pharmaceutical form of vitamin D that doctors prescribe for their patients, is as effective as vitamin D3 in maintaining a person’s vitamin D status, i.e., blood level of 25-hydroxyvitamin D.  Trang et al 1998 gave healthy adults 4,000 IU of vitamin D2 or 4,000 IU of vitamin D3 in alcohol for two weeks.   A comparison of the blood levels of 25-hydroxyvitamin D after two weeks revealed that there was approximately a 50% difference in the group receiving vitamin D3 (being approximately 50% higher) than the vitamin D2 group.  This implied that vitamin D3 was more effective than vitamin D2 in maintaining circulating blood levels of 25-hydroxyvitamin D.  Armas et al 2004 gave a single 50,000 IU dose of either vitamin D2 or 50,000 IU dose of vitamin D3 to healthy volunteers during the summer and observed that the group who received vitamin D2 had a more rapid drop in their circulating blood levels of 25-hydroxyvitamin D.  They also observed that the group that received vitamin D2 had a more rapid drop in their blood levels of 25-hydroxyvitamin D3 compared to the placebo group suggesting that vitamin D2 was not only less effective than vitamin D3 in maintaining circulating levels of 25-hydroxyvitamin D, but also that vitamin D2 increased the destruction of vitamin D3.

Based on these observations, physicians, health care professionals and patients have made an effort to find vitamin D supplements that contain vitamin D3.  However, in the United States, only vitamin D2 is available as a pharmaceutical preparation, and, thus, patients who are vitamin D deficient and treated by their physicians receive vitamin D2.  I treat vitamin D deficiency with 50,000 IU of vitamin D2 once a week for eight weeks.  To prevent vitamin D deficiency from recurring, I then put the patient on 50,000 IU of vitamin D2 every two weeks forever.  From my experience of over 100 patients on this regime for up to six years, their blood levels are sustained above 30 ng/ml which is considered to be the vitamin D sufficient range.  On average, the blood level was between 40-50 ng/ml.  Furthermore, an evaluation of their blood calcium, a measure of whether ingesting vitamin D2 at these levels, had caused any toxicity did not change.  Therefore, this regime was effective in maintaining my patients’ vitamin D status without causing any untoward toxicity.

To determine whether vitamin D2 was as effective as vitamin D3 in maintaining circulating blood levels of 25-hydroxyvitamin D, a study was conducted whereby healthy adults received either 1,000 IU of vitamin D2 or 1,000 IU of vitamin D3 in a capsule once a day in the winter for 11 weeks.  In addition, one group received a placebo capsule and one group received a capsule that contained 500 IU of vitamin D2 and 500 IU of vitamin D3 daily for 11 weeks.  Blood levels of both 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 were determined by state of the art method using liquid chromatography tandem mass spectroscopy.  Holick et al, (Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D, J Clin Endocrinol Metab  93:677-681, 2008;) reported that the blood levels of 25-hydroxvitamin D rose to the same degree in the healthy adults who took either 1,000 IU of vitamin D2 a day or 1,000 IU of vitamin D3 a day for 11 weeks.  The group that received vitamin D2 also had their blood level of 25-hydroxyvitamin D3 measured.  There was no significant drop in the blood level of 25-hydroxyvitamin D3.  To determine whether the mixture of vitamin D2 with vitamin D3 would alter the blood levels of 25-hydroxyvitamin D, the adults who received 500 units of vitamin D2 with 500 units of vitamin D3 also raised their total blood levels of 25-hydroxyvitamin D3 in an almost an identical manner as the adults who received 1,000 IU of vitamin D2 or 1,000 IU of vitamin D3 a day for 11 weeks.  The authors concluded that ingesting 1,000 IU of vitamin D2 or 1,000 IU of vitamin D3 a day during the winter (at a time when sun exposure had no influence on blood levels of 25-hydroxyvitamin D) that both vitamin D2 and vitamin D3 were equally effective in maintaining the blood levels of 25-hydroxyvitamin D.  Furthermore, vitamin D2 did not have a negative influence on serum levels of 25-hydroxyvitamin D3.  Adults who took 500 units of vitamin D2 with 500 units of vitamin D3 had similar increases in their blood levels of 25-hydroxyvitamin D suggesting that vitamin D2 taken with vitamin D3 does not have any negative influence on the metabolism of vitamin D3.  

The authors reviewed in their Conclusion several studies that had previously reported that vitamin D2 was as biologically effective as vitamin D3 in both pregnant women and in healthy adults.  This study confirms these observations and adds to the body of scientific literature demonstrating that at least when healthy adults take 1,000 IU of vitamin D2, they can be assured that it is as effective as taking 1,000 IU of vitamin D3
************

Although this a little academic, since I have been perfectly happy with D3 for years, a resolution would be iteresting.
Any chance of an update, or a Holick interview here?
MikeV

The reduced appetite after wheat withdrawal is exactly what I'm experiencing. A very low carbs (and so very low wheat) diet is the first diet that I can stay on because I don't get hunger pangs. I'm down about 20 lbs. (10%) since finding this blog and going wheat-less.

Hmmm... I've been wheat free (grain-free, actually) for almost 3 weeks now. I started off being mildly hungry all the time, and that has faded. I wonder if that's what you're talking about there!! Terrific!

Keep the articles coming... love them.

Diana

I started just before Christmas. The first week or so was unpleasant ... hungry, groggy ... wheat withdrawal. The "no hunger pangs" showed up after that and made it possible for me to stay on this diet. It's the first time I've been able to consistently lose weight.

When I first went off wheat it took a good 3-4 weeks for the withdrawl to stop.  During that time I was ravenously hungry and ate constantly.  I know my body was just hoping I'd eventually eat some bread.  I gained probably 10 pounds, but it came back off (I don't have any other weight to lose).

Was that a study you are referencing or clinical experience?  Would love to have more details.

Biblical wheat and remote regional "landrace" wheat strains are not the same as tetra-ploid wheat we're sold. Tetraploid varieties have been grown for less than 500 years; and di-ploid varieties around for 500 to 1,000 years.

Look, I'm glad that this works for some/lots of people - but I've been doing this since before Christmas, 4 months now, and I haven't lost a pound.  My status is a good deal worse in a number of subtle and not-so-subtle respects, and frankly nothing of substance has actually improved in any way.  Recommendations of iodine supplementation were an unqualified disaster.  And I effectively have nowhere to go, now -- I'm stuck with this mode, because I have every reason to believe that going back to grain in any degree will yield uncontrollable weight gain.  I'm really not trying to be negative, but the point  has to be made, amid all the rosy predictions of magic pounds disappearing (that's just calories-in-calories-out which is supposed to be BS, according to the new Received Wisdom, no?) that this regimen doesn't work for everyone.

How is wheat different from just carbs in general? Don't they all create this problem?

"...has its very own withdrawal syndrome should you miss a 'hit.'"

If you follow the link, you'll see that this unqualified statement is based on self-selected (Dr. Davis's blog commenters) anecdotal evidence.

brec:

If you keep following those links back, you'll eventually land here:

http://www.jbc.org/content/254/7/2446.full.pdf+html

I agree. I can't stop once i start eating crackers or croissants.

In your opinion, do other grains like corn and rice have the same effect?

@Megaera

I used to eat a lot of bread. For the first four months of my grain-free and carbs-from-veggie-only life and policing my blood sugar I gained about 10lbs. My NMR profile got significantly worse, too. Dr Davis checked my APOE and it was type 4, so he told me to limit fats and changed my medications. In addition, I stopped being a vegetarian and increased the amount of lean proteins in my diet. I also changed my exercise routine according to slow-burn. Four months later - 14 lbs have been lost and NMR profile improved drastically.

I am saying it, because there is a happy path of losing weight when you stop eating wheat, but certain people may need to make an additional effort. So you need to look further.

Japanese children (290) aged 5 - 18 had MRI of brain to see if breakfast centered on white bread vs. white rice differ. The study adjusted for confounding factors.

The older white rice breakfasters showed a larger grey matter in relation to cranium volume; in some brain areas white bread eaters had more grey matter.In the youngest there was not a statistical differenece in grey matter volume between the groups.

Rice breakfasters' MRI showed more grey matter in left superior temporal gyrus, left inferior temporal gyrus,right pre-central gyrus, left superior caudate  nuclei and the bilateral caudate nuclei. Caudate volume is associated with a subset of verbal IQ ( POI component); the rice breakfasters had higher POI scoring. And in addition they had higher IQ than the bread group; IQ is associated with prefrontal and orbito-facial corteces and the cingulate gyrus.

Bread breakfasters MRI showed more grey matter in the postcentral gyrus, right precentral gyrus, right fronto- parietal orbit, and bilateral orbito-frontal corteces. Their MRI showed more white matter in
the right pre-frontal gyrus  and post-central guyrus; otherwise the two diets showed no white matter % differences between the groups.

My experience has been exactly like Steve's. Since going completely wheat-free (as well as ditching the sugar and most fruit), I'm down 15 lbs. and still losing. The best part of all is that my hypoglycemia symptoms have completely disappeared, my energy is through the roof, and I no longer get uncontrollable hunger pangs.

As Steve and 1st Anonymous point out, this approach can work for many, if not most, people with extravagant weight loss and health benefits.

However, as the frustration expressed by Meg suggests, there may be confounding factors. As Gene points out, apo E4, for instance, can modify the response. But this was not the focus of the post.

This is a blog. Each post makes a point. Don't mistake this for a one-on-one healthcare encounter.

Hi, Real Food-

I was referring to the collective experience demonstrated in gluten-elimination diets in celiac patients.

I will summarize this literature in my upcoming book from Rodale, Wheat Belly.

I've relented and switched from oats to swallowing about 1 oz of chia seed for breakfast.  The rest of the day I mainly rely on cabbage/veggie soup (no starches)...snack on roasted peanuts & boiled eggs.  Am losing weight.

Dr. Davis - I posted today about leptin resistance, and how high triglyceride levels have been implicated in stopping leptin from its normal "hunger stopping" function. Have you seen a dramatic decrease in triglycerides from those that simply refrain from wheat, without intentionally counting other carbs?

A few months ago, I read a post on this blog which suggested getting a BG meter in order to see what effect things like wheat had on BG. The results of my first meal (whole wheat pasta with red sauce, broccoli, and whole wheat toast) showed 183 at 1hr PP and 149 at 2hr! What was really surprising to me, however, was that despite the 2 hour number being as high as it was, I was still very hungry.

Based on this and subsequent tests, along with increased awareness of satiety, I've made some pretty significant changes in the types of foods I eat. Mostly, I've cut back on all the grains (even "whole grain") and added fats (I no longer believe the "low fat" recommendations).

The result is that in about 3 months I've lost roughly 15 lbs. (mostly in my belly), despite having no sense of being deprived. It doesn't hurt that my lipids have improved, as well (TC, LDL and trigs all lower).

I had been skeptical of Dr. Davis's claims about wheat at first, but I am now convinced that for me at least, wheat is not my friend.

What if that happens to me with prety much every thing. I want another almond, another egg, another piece of cheese, another wine, more chocolatte, another sushi, a bit more of meat....

I started to cut down on my bread intake about 3 years ago and am now almost completely grain free (apart from accidental consumption). I have lost over 50lb and feel like a diifferent person.

One of the biggest bonuses of cutting wheat from my diet is the improvement in my mood and temperament. I used to be quite a moody and slightly unpredictable type of personality, but now everything is calm and serene.

Quite a few scientific papers show a connection between schizophrenia and cereal intake. http://healthydietsandscience.blogspot.com/search/label/Cereals%20and%20Schizophrenia

This may help to explain the improvement in my personality.

I've been mostly wheat-free for over a year, and have lost exactly zero pounds. I still don't eat it, since I believe there are a lot of benefits to leaving it out (all my blood-work #'s were fine before, but improved a bit more after awhile of high-fat/low carb). The biggest improvement I've seen is in my mood -- no more depression. However, I'm still 100 lbs overweight.

When wheat products are removed from the diet--without calorie restriction, without counting fat or carbohydrate grams, no exercise program, no cleansing regimen, no skipping meals . . . nothing--calorie intake drops 350 to 400 calories per day. This calorie figure remains curiously consistent across multiple studies in which wheat was eliminated.


I would be interested in one study demonstrating that just cutting wheat from the diet resulted in 350-400 cal/day spontaneous reductions in intake.  Preferably controlled for protein content by substituting other carbs for normal wheat content.  

The VLC diet studies don't count as too many variables are changed there to attribute most, if even any, of the decreased intake to reductions in wheat intake.

If wheat is addictive, and whole wheat supposedly contains more addictive substances, why don't people gravitate towards whole wheat pasta and bread and binge on
those?

For amateur epidimeologists:

per capita wheat consumption by country

CarbSane-

You stated "The VLC diet studies don't count as too many variables are changed there to attribute most, if even any, of the decreased intake to reductions in wheat intake."

Same could be said for the studies that cholesterol and fat are the sole reasons for our obesity, diabetes, heart disease, etc- yes?

I also don't buy your suggestion that people don't binge on whole wheat containing foods as I've seen it countless times at bagel shops, healthy Asian noodle bowl places, pizzerias, etc. People trying to eat "Healthy" often over indulge on "healthy" pizzas, bagels, breads and pasts all while thinking they are doing eating exactly what the AHA recommends. Something that is more than likely silently killing them.

I've done all this before and all it got me was a plethora of trips to a cardiologist, anxiety, depression, bloating and countless Rx pills that did absolutely nothing. And I'm not an unhealthy guy by any means.

You may feel Dr. Davis' posts are all anecdotal and that's fine. His new Track Your Plaque book has all the evidence and studies I need to support his claims and it was the anecdotal evidence that he posts that spoke volumes to me. It was the first place I found that explained exactly what I was going thru (30 years old, extremely hypertensive, depressed, slightly overweight and angry with atherosclerosis that seriously a 30 year old should not be suffering from). From that point on I've read his book, followed his plan and have replaced all my worthless Rx's for a daily dose of VD3, Omega3 and steer clear of "Healthy" grains... and I couldn't be happier.

Of course this is my own "anecdotal" experience, that four of my previous cardiologists couldn't achieve...

In posts above I didn’t make clear that I am actively “dieting” as in “trying to lose weight”.

My diet: Two Atkins shakes for breakfast with vitamins and two more for lunch. An Atkins shake for snacks, as needed. Dinner is a leafy greens salad with vinaigrette and maybe nuts, peppers, tomatoes, cheese, minced garlic plus a meat portion and sometimes a low-carb vegetable. A 30 minute after-dinner walk with my dog most  evenings. A 15 minute walk/run some mornings before my weigh-in.

I believe the only reason I can stay on this tough diet is the “no hunger pangs” effect that I get with very-low-carbs. For example, I can have the Atkins shakes for breakfast and easily go until lunch with no cravings. To accelerate weight loss, I can even skip breakfast – no hunger pangs means I can go from dinner to lunch without cravings – I’m hungry but I can do it – I’ve done it every day this week.

I’m about 5’8”. I found this blog on Dec. 17th and I weighed 204 lbs. On Jan. 29th I weighed 189. Today, April 8th, I weighed in at 179.8! I hadn’t been in the 190s in years. The 180s? The 170s? They were just dreams to me.

I have gone off the diet; typically after multiple social events in a row. Example -- alumni social Thursday eve, extended-family dinner at a restaurant Friday eve, sports event Saturday, why-not-keep-eating Sunday. Then, I want to keep losing weight so I get back on the diet. I go through wheat-withdrawal again but now I know it’s just a temporary phase and that helps me get through it. It takes about 10 days to get back to where I was and then I keep dieting.

Disclaimers – On a tough diet like this I am weaker than normal but I can function and I put up with it because, after my initial success, I see this works & I want to lose the weight. I have a desk job so I can probably better handle the reduced energy levels than someone with a more active job. My family is supportive and we eat dinners that work with the diet. So I have intangible factors helping me.

One definition of hack is “a clever solution to a tricky problem”. To me, very-low-carbs is an empowering “hack” of my metabolism that lets me control my weight. Hallelujah!

A single variety of modern tetra-ploid wheat has 100s of different gluten proteins. This equates to 10s of thousands of variations of peptide sequences one can ingest from wheat.

The molecules formed depend on how trans-amin-dation (cross linking proteins) binds the free residues of glutamine. This potential bond is genetic for each strain of wheat, since involves the positioning of Carbon terminals (located on any of those peptides, as a proline residue). Tetra-ploid wheat has many unique proline residues that cross-link (ex: alpha gliadin) in a way that can resist our digestion.

Plasticity is a term used to describe the human brains ongoing adaptability. The nerve axons are in a outer (extra-cellular) matrix of gluco-proteins; this includes the proteo-glycan chondroitin sulfate ( glycan = poly-saccharides & oligo-saccharides; hence "glyc-").

Chondroitin sulfate's residue (wing) of N-acetyl-galactos-amine provide a place for lectins to bind to (ex: lectins most infamous  trans-amididation incarnation is the gliadin molecule, a type of glyco-protein). Thus different glyco-proteins, with unique derivative glycos-amino-glycan molecular chains are going to affect brain neurons differently.

Anti-bodies for uOR (natural opiod receptor)detected in circulation are indicative of a reaction to some lectin. This means a lectin is binding to the uOR; Doc calls this an "exorphin effect" with one end result being appetite stimulation.

Neo-striata cells in the brain work off of input from the cortex; the neo-striatum has a part called the matrix (note: here matrix is a brain structure & not to be confused with terms like extra-cellular matrix) and another part called the striosome. The matrix neo-striata gets input from the pre-frontal brain and senori-motor regions; while the striosome input is from pre-limbic, infra-limbic and pre-motor corteces.

The matrix neo-striata neuro-chemistry is  integral to behavior involved in self-initiated action, goal directed behavior, sensory integration and motor programs. During post-natal (growing child) brain development the striosome neo-striatum cells have a high degree of involvement with glyco-proteins; which may partly explain the Japan school children brain development differences due to breakfast of rice vs. bread (detailed above).

@Eric, I agree.  Don't know where I've claimed such.  Dr. Davis made a claim (and he preceded that with "When wheat products are removed from the diet--without calorie restriction, without counting fat or carbohydrate grams, no exercise program, no cleansing regimen, no skipping meals . . . nothing-").  Study?  One?  

I'm just asking for a study that demonstrates this claim.  I don't refute that a good many people could benefit from avoiding wheat.

My apologies CarbSane, I didn't mean for reply to come across as combative.

Dr. Davis may have a study that he can refer you to.

But it is a well known fact that foods that trigger a surge in blood sugar and after-meal crashing also lead to increased hunger more frequently.

Foods that lead to the surge are carbs in (either healthy or processed) grain or sugar form.

Sometimes all the anecdotal evidence should stand above the biased studies attempting to maintain the status quo. Just my .02

I reduced my CHO intake about three years ago and lost about 8 pounds in the first three months.  At about the three month point, I removed wheat and all other grains from my diet.  I have lost no additional weight since I gave up wheat.  

I would say that I have not reduced my caloric intake by 400 calories a day.

@Eric, no apology necessary, I didn't take your post as combative at all.  I just find Dr.Davis making sensationalistic claims a matter of routine lately.  I do a lot of literature searching and I've not, to my memory, ever come across one study that just looked at eliminating wheat and intake.  I'd be curious to see the results of such a study done in a well controlled manner.

In response to several commenters:

Citing studies in which calorie intake is reduced by strictly eliminating wheat while not imposing any other restrictions does not necessarily mean that this is the most healthy way to eat.

In other words, if I eliminate wheat but replace lost calories with corn chips, jelly beans, and Coca Cola, then of course I will not lose weight nor obtain health benefits beyond elimination of gluten and other undesirable ingredients in wheat.

A better approach would be to 1) eliminate wheat, then 2) reduce carbohydrates, especially cornstarch, oats, and sugar, then 3) eat other whole healthy foods.

My point is that, sans wheat, the drive for consumption is diminished for many, though not all, people.

MRI of adult brain while eating shows a response according to an individuals BMI variation. I had this as a well composed comment at WholeHealthSource, but can't retrace it; so, roughly, from my notes now.  

High BMI individuals have more brain activity in the left posterior insula, supramarginal gyrus, para-central lobule and the cerebellum's uvula/declive/tonsil structures. Cerebellum response involves how one likes the looks/smell of food; more blood flowing in the cerebellum coincides with increased appetite.

Low BMI individuals have more brain activity in the anterior insula, posterior hypothalamus, amygdala, thalamus, pons and mid-brain structures.

The Vagus nerve (dorsal) leads from our "gut" up into the pons sub-nucleus of our brains dorsal raphe. In obese individuals this link shuts down when eating. Contrary to the obese, this link is open in lean individuals when they (non-obese) are eating.

The Pons, which inputs into most of the other brain structures, shows more functioning with slower eating. In addition, stuffing with excess food in a meal slows the pons interaction with the brain.

The Amygdala, part of our limbic system, sets the emotional response to things ingested. It gets plenty of neuro-signals from the gut, and is implicated in binge eating.

The Posterior Insula recieves input from both the amygdala and hypothalamus (regulator of amount we ingest). In obese individuals both the posterior and middle insula trigger (on)into action when they see the meal; as contrasted to normal BMI individuals, where these brain structures remain unaffected when they (non-obese) see a meal.  

In obese individuals there is comparatively more dopamine activity in the neurological circuits of the hypothalamus, amygdala, mid-brain and thalamus (arousal response). So, all in all, it seems quite possible Doc's nemesis (tetra-ploid wheat's molecules) can play antagonistic roles in the brain.

But Dr. Davis, you said there are multiple studies demonstrating a similar drop in caloric intake from eliminating wheat "without calorie restriction, without counting fat or carbohydrate grams, no exercise program, no cleansing regimen, no skipping meals . . . nothing-"

Are you walking that back?  Or do such studies exist.

Hi CarbSane,
Doc's rant is about the "undesireable ingredients"
in modern wheat. If would you forgive me for sounding like a know-it-all, then, my comments show some brain responses that go beyond "x" number of calories, "x" amount of carbohydrates, "x" level of exercise and "x" amount of meals.

It is modern wheat's assorted agglutin fractions, the way they bind glycans (like chitotriose, Beta-1-4-linked N-acetyl glucosamine) and how they cleave off "rogue" metabolites that has an effect on the brain cells. These metabolites have to get inside the brain cells cytoplasm by trans-duction; they are not ions.

These "undesireable" cleaved metabolites have exposed glucosamine (GlcNAc) wings (residues) that bind to GLcNAc receptors on the cell; this fosters their trans-duction (carrying) past the cell membrane and any intervening endothelial (blood vessel wall) barriers.

The "undesireable" metabolite then out binds Lysosome C; thus normal lysosomal "housekeeping" endo-cytosis (engulfing) action is inhibited from destroying (ie: no opportunity to hydrolyse apart bonds in the metabolite) that metabolite. This gives the metabolite the time to act like a Heat Shock Protein (ie: it has
physically blocked that brain cell's usual heat shock protein ever since it locked onto that cell's GluNAc receptor); and thus, that "undesireable" metabolite can ferry (translocate) it's glycan/peptide right to the Endoplasmic Reticulum inside of that brain cell.

Once the endoplasmic reticulum
(in a brain cell) recieves an
"undesireable" peptide/glycan complex it (endoplasmic reticulum) is not able to do a
"normal" job with it; which job is to properly fold (ratchet into explicit configurations) the normal proteins the  brain cell passes to it (endoplasmic reticulum). Any alternate fold in a protein means it (protein)will react differently in the cascades it participates in.

How this translates into each of the physical alterations in specific brain structures that I mentioned is beyond my understanding. This comment is to explain one of the ways those
changes can get initiated in human brain cells by modern wheat; and also, to show our schooling on calories/carbs/ exercise/meals/cleansing misdirect us Doc insists he sees clinical results.

@Might,

I have enjoyed many of your comments; you have a keen talent in selecting and presenting information which dovetails nicely with Dr. Davis's blog entries. I found this one particularly fascinating.

Thanks!

Here is my wheat story. I have been "mostly" avoiding wheat for 3 years and when finally being diagnosed with Hashimoto's decided to go completely wheat free. My doctor suggested a gluten challenge for a definitive diagnoses of celiac or gluten intolerance.  Unfortunately, I agreed. Six weeks into the 3 month challenge I quit due to problems that began during the gluten challenge (joint pain, severe digestive distress, insomnia, adhesive capsulitis, nightsweats). Unfortunately the gluten caused some damage and I developed new food intolerances to dairy and nightshades, which have not resolved in 7 months of being grain free.

Sorry this reply comes so late! I hope you see it. May I suggest that you try magnesium oil? It's a mixture of mag chloride and water that you apply to your skin. You may be mag deficient and, if so, that could explain why you're not losing weight.

Hi Dr Davis,
I am an apoe4 carrier. My trig=62, HDL=69; LDL-C=175 after 16 months on a carbohydrate restricted, gluten free diet. Wondering whether I need to also reduce my fat intake. But then what is left to eat? Making up the calorie difference with protein does not sound too healthy.

David

Hi, David--

I would urge you to NOT rely on the calculated LDL value, since on a low-carb diet with potential conversion of small to large LDL particles calculated LDL can substantially overestimate true LDL.

The best: LDL particle number through NMR lipoprotein analysis. The next best: apoprotein B, widely available from nearly all labs.

When you're armed with this information, then you can make an intelligent decision about diet changes.

Regarding Item 6

There was some traffic between Chris Kresser and Jimmy Moore on Twitter yesterday regarding whether low carb caused low T3 in susceptible individuals. Clearly bad news for heart health.

I am a treated hypothyroid and this was my recent experience - I had gone low carb and ended up with an abscess in the roof of my mouth that needed antibiotics.  When tested, my T3 had fallen from 5.5 to 3.8 (RR 4 - 6.8) - however, my TSH was 0.672 (RR 0.35-4.5).  In the UK, this low T3 would normally would have been missed as there is a TSH only testing policy here unless the TSH is found to be outside the reference range - I elected to pay privately for the T3 test.

I remain on low-carb (and wheat free of course) as it is the only approach which allows me to lose weight, and have increased my meds from 75T4+20T3 to 100T4+40T3.

I would query whether you consider hypothyroidism to be rare. I suspect it is very common.

Hi Dr. Davis:
What if the patient  followed the above diet, had a particle count of 2,100, but only 200 were small and HDL 69 and Trgs 66.  Would this be acceptable, and better than a particle count of 640, less than 90 small, HDL 64, Trgs 45, but on statin and Zetia?  Assume thyroid and D all normal, and Apo E3/3
Thanks for all the input

Hi Dr Davis,
This post really hit home with me (and ironically this is my first visit to your site).  I had a heart attack 2 years ago (34 years old, ate well or so I thought, in great physical condition at 5'9" 150 lbs).  My cardiologist advised the usual low fat diet and pravastatin, and while my lipids are better than they were, I'm still very concerned they are not near where they should be.

About 5 weeks ago I found the primal diet and began eating that diet.  Last week I had another lipid test and my numbers actually got worse (not by much).  Would you mind reviewing my numbers and if you have any suggestions I would appreciate it.

8/31/2009 heart attack
total chol 115
LDL 74
HDL 16
Triglycerides 126
VLDL 25

07/19/2010 checkup
total chol 138
LDL 64
HDL 33
Triglycerides 203
VLDL 41

03/21/2011 Healthfair
total chol 122
LDL 69
HDL 31
Triglycerides 111
VLDL 22

8/19/2011 walk in lab:
total chol 159
LDL 98
HDL 34
Triglycerides 135
VLDL 27

Glucose 97
hsCRP 1.2
A1c 5.5

Do you suggest giving the "primal" diet more time or do you suspect I may have another condition causing this?

Also in May of this year I had the following tests done at the cardiologists:
Date of service: May 13, 2011
CAT Scan MRI & NMR
Diagnostic Radiology X-Ray
Cardiovascular Stress Test

I was told everything was fine.

Track Your Plaque once gave a desirable level of ApoB  as under 70 mg.dl as surrogate marker for the desirable LDL particle number (which is less than 700 nm/l) if one only has ApoB testing.  Maybe some one else can recall the conversion ratio of ApoB into LDL particle numbers.

A cholesterol fractions normal transfer from HDL to ApoB is governed by  the cholesterol ester transfer protein (CETP). Genetic variants of CETP can cause differences in the numbers of  small LDL and sparse CETP can cause cholesterol to stay stuck in HDL  ( CETP has little impact on numerical % of HDL). So genetic variants of ApoB can influence the levels of cholesterol shunting around.

In  the liver ApoB normally gets it's lipids when ApoB goes into a cell's endoplasmic reticulum. And if the ApoB doesn't improperly degrade ( ApoB needs "enough" microsomal triglyceride transfer protein SREBP-1c, the sterol regulatory element binding protein, to avoid degrading) then ApoB can pick up triglycerides to form VLDL molecules. So, if there is not enough liver SREBP-1c  then lipids can't be transferred over to make triglyceride rich VLDL; conversely lots of liver SREBP-1c provokes extra VLDL.

Doc says carbohydrate related  post-prandial high glucose not only induces  more VLDL output  from the liver but that this is part of the mechanism whereby carbs can boost body fat. High carbohydrate intake causes extra lipo-genesis in the liver because a significant  reflex of high post -prandial liver insulin is a signal that upregulates SREBP-1c. Then SREBP-1c expression rises and that in turn activates genes for the lipogenic enzymes (ex: fatty acid synthesase & acetyl CoA carboxylase),

Rogue readings of VLDL may be due to viral hepatitis proteins, flavivirus and pestivirus, which can decrease VLDL formation and secretion while dropping levels of ApoB. Viral proteins "smear" onto lipids and this blocks SREBP-1c action and viral proteins can also "stick" on to the HDL protein fraction ApoA1 inside of the  liver cells' Golgi Apparatus. Thus in chronic liver disease and hepatitis circulating VLDL associated triglycerides eventually decreases so there are more non-VLDL  triglycerides in play.

Hi Dr. Davis,

I was just wondering, due to many healthy cultures including the kitava, okinawan's...etc, who indulge in rather high carb intakes and retain rather pristine health, is it possible that high trigs, low hdl..etc may just be a lipid profile reflecting high carb* intake rather than suggesting atherogenic buildup ?

*when based on safe starchy type carbs

Hi, Paul--
In the population I see, hypothyroidism is exceptionally common, both in people on low-carb but also in people prior to initiating their low-carb efforts. So, without a formal analysis, I'm skeptical that low-carb in and of itself causes free T3 to drop.
There are also numerous inhibitors of the 5'-deiodinase enzyme that converts T4 to T3, including perchlorate residues from fertilizers in vegetables and polyfluorooctanoic acid, the residue of non-stick cookware, just to name a couple.

This is the BIG unanswered question. Sadly, there are next to no data that speaks to this question.
My day to day answer has been to 1) eliminate small LDL, then 2) maintain LDL particle number 1500 nmol/L or less. But that is pure speculation on my part.

Hi, Chris--
Something doesn't compute: Every panel you list is the pattern of excessive carbohydrate consumption and/or sensitivity. So something is sneaking through. There is no question that a "primal" or low-carbohydrate approach works for this pattern.  

You might also have an Apo E2 gene that amplifies carbohydrate sensitivity.

Hi, Might--
As always, you are an incredible fountain of unique insights!

Sorry, Jack, I didn't understand your question. Could you rephrase?

Thanks.  I've only been eating primal/paleo for about five weeks, so only the last panel would reflect this (if thats enough time to be reflected in my lipid panel).  I will re-test after another few months.

Dr Davis. Jeez. This sounds similar to my story (Frustrated's #s). I have eaten Paleo for over a year now, I have done exceedingly well with body composition in that time. See my "Share You Paleo Before and After" here ---> http://paleohacks.com/questions/7058/share-your-paleo-before-and-after/28493#28493. But this only adds to the confusion for me (and others).

For some reason, my labs came back on July 8, 2011 with small dense LDL and pathetic HDL at 40, despite a diet rich in GF beef, pastured eggs, bacon, pasture butter, coconut oil, ghee, veggies, starch and fruits only for carb sources, etc etc. I spend mega money to eat well. We don't mess around. I posted my VAP panel results on PaleoHacks last month and it has resulted in a lot of attention on this very subject. Chris Masterjohn weighed in with his thoughts. Dr Kruse wrote a blog all about it.

http://paleohacks.com/questions/50347/hack-jack-kronks-vap-test-results

I will be retesting again in about a month, as I have made some changes, like eliminating bananas, less heavy cream and pasture butter, etc.

My lab said it's $390 just to do the ApoE test. Is this a normal price? If not, where do you recommend people get the testing done?

I'm genuinely confused. It's like my body is saying... "Yes Jack. Good job. I am very happy with what you are eating. I will continue to keep fat off and pack on muscle." But then my heart is saying "Nooooo. Stop!!"

How can this be?

I was questioning if your pathological interpretation of a blood lipid profile that exhibits low hdl and high triglycerides, could instead just be a reflection of a high carb diet rather than suggesting an increased risk for CVD. I was referencing a couple high carb cultures, such as the Okinawa and the kitava, who exhibit a similar lipid profile but have very small incidence of CVD. Compared to other cultures with similar lipid profiles, such as the Swedes and Americans, who have much higher rates of CVD would suggest it's more about quality of blood lipids rather than their certain partitioning. Hopefully that's a better re-phrasal?

This is the BIG unanswered question. Sadly, there are next to no data that speaks to this question.
My day to day answer has been to 1) eliminate small LDL, then 2) maintain LDL particle number 1500 nmol/L or less. But that is pure speculation on my part.

My understanding related to your above comment is that large LDL is nearly as athrogenic as small LDL and that you want the particle number low with mix between largle and small LDL taking secondary importance.  Of course, that is based on a diet that the avg american consumes,  and not on the low carb with wheat sugar and cornstarch elimination you advocate.
Am i under a correct understanding regarding large LDL being dangerous as well and therefore the need to minimize this even with your dietary recommendations?  Also, i thought you advocated a total LDL particle number to approach 600?  Is your 1500 number a revised viewpoint based on newer diet or clinical observations?
Thank you again.

Server error blocking me again ... testing after hour passed.

ApoE is crucial to VLDL & chylomicron formation. Variant ApoE 2 less efficient at transfering lipids to liver and is binding lipids up an extra +/- 2%; result is that lipids take longer to clear from circulation and more can go wrong. From my notes, here is the rate some ancestral populations have at least 1 copy of ApoE2: 2-4% of Mexican-american & American Indian, also  3-4% of Japanese & West African. There is 0% of South American Indians with ApoE2 and one wonders which variation of  ApoE  might be in Kitava melanesians. .
ApoE4 degrades easiest of all ApoE forms, leaving protein fragments in cell's cytosol which then can affect a mitochondria's lipid binding region impairing the performing of  tasks. In addition ApoE4 fragments diminish gene PPAR gamma expression; and this depresses the desirable bio-genesis of mitochondria. The affects on mitochondria may be why high levels of dietary fat is problematic for ApoE4 individuals; there may be too sparse output of viable mitochondria and mitochondria membranes are involved in how efficiently we burn fat or glucose.  .
In light of these ApoE4 nuances it is interesting to know that fasting raises free fatty acid levels (from fats in the body and not loose fats from recent food); and then those free fatty acids upregulate  gene for PPAR gamma in the liver. Fasting makes one put out ketones  because of the extra PPAR gamma programing and this ketogenesis is also one way that activating more PPAR gamma improves insulin sensitivity. This suggests to me that individuals with ApoE4 may (?) find some benefit from modified fasting; possibly something like decidedly fewer meals in a day and also simply not grazing on snacks (ie: in addition to just trying to select what foods to eat) between meals that are regularly spaced apart (ie: very early breakfast to let meal times spread put more evenly) .

Finally again from my notes, here is the rate some ancestral population have at least 1 copy of ApoE4: .14-19% Germans & Finns, also 7-12%  French & Italians. Of course America is one of the world's melting pots so an individual's propensity for ApoE 4 & ApoE 2 is hard to pin point.

This is fascintaing Might. I have been guilty of snacking too much. All healthy snacks, but still the concept of grabbing bites of delicious foods between meals might be messing with my liver. For my VAP test, I did not fast. Chris Masterjohn believes this was the reason (or at least the reason for dismissal) of my increase in triglycerides in the blood. I am most concerned about my low HDL, because if I raise my HDL, I believe my LDL will become more dominantly pattern A.

Thank you for the reply.  I would like to share a speculation.  Strict low carb means gluconeogenesis means an increased cortisol demand? OK in young fit Paleo men, but what about long-term un(der)treated hypothyroid individuals?

In "Safe Uses of Cortisol", Dr William Mck Jefferies (p. 183/4) observes that low dose (20mg/day) of hydrocortisone taken by a patient with hypothyroidism increases T3,  lowers T4 and improves patient energy levels suggesting such low dose cortisol enhances T4 to T3 conversion.

Could VLC, by putting demands on potentially weakened adrenals, have the opposite effect?

HDL molecules hold triglycerides (there are 45 different variations of triglycerides in circulation, which are based on what their esterified fatty acid component is), cholesterol esters (about 13 - 27% of the HDL surface particles), shingomyelins and glycerophospholipids. HDL's principle proteins are +/- 70% ApoA1 and +/- 20% ApoA2;  yet any changes in the ratio of ApoA2 from genetics (Kitavans?, I propose so) or drugs (ex:fibrates) can have effects.  

Usually people with low levels of  HDL have more trigs on their HDL surface (compared to those with high levels of HDL) and low HDL is associated with the passing of more cholesterol esters to VLDL & chylomicrons. Also, when HDL trig levels go up that makes it easier for the liver enzyme hepatic lipase to cleave off more ApoA1 for the kidneys to clear away; and that further tends to keep HDL levels low.  

In comparison people with high levels of HDL have more cholesterol esters on their HDL; which may be due in part to cholesterol esters affinity for ApoA1 in HDL. And statisticly high levels of HDL are usually associated with bigger ("large") HDL molecule size. Both large HDL and ApoA1 are considered to be more protective factors against atherosclerosis.

I suspect that Kitavan melanesians' low HDL fortuitously correlates with a geneticly higher than normal % of ApoA2; and ApoA2 configures more deeply nestled into the HDL complex than ApoA1. It (ApoA2) influences molecular  interactions all the way to the HDL surface and limits certain lipid dynamics.

ApoA2 holds ApoA1 off of mature HDL molecules and this results in a shunting of ApoA1 into forming up the pre-Beta HDL; these lipid poor ApoA1 configurations are great at doing reverse cholesterol transport that brings back cholesterol  to the liver for excreting as bile acids. Those pre-Beta HDL are small, yet notably excellent at taking cholesterol away from nefarious macrophage foam cells (the large HDL  molecule also picks cholesterol nicely from foam cells).

Experiments see that preceeding type of change with fibrate drug doses, which only minimally raise HDL & ApoA1 yet increase the ApoA2 amount in HDL by over 25%. Since fibrates are agonists activating the peroxisome proliferator activiated receptor PPAR alpha it might be instructive to see if anything in the Kitavan diet is a similar agonist, such as heirloom tuber roots derived from wild yam with high diosgenin content (diosgenin is well known to affect PPAR gamma).

Thanks for the excellent post! Bookmarked! Will come back again…

Hi, Steve--
There really is no final word on what the desired endpoint is when small LDl has been eliminated and you have pure large LDL. In a perfect world, I'd wish for a particle number of 600 nmol/L with pure large LDL. But I'm no longer entirely sure this is necessary. But this remains anecdotal. There are no formal data, nor do I have any formal analysis of our own data on this question.

Hi, Jack--
Don't know, since I've never seen any genuine lipoprotein data on these populations. Most of the data I've seen has been total cholesterol, which is far too crude to draw any conclusions from.

Have you seen lipoprotein data on these populations?

Might. Do you suspect that I have low HDL and highish Trigs/VLDL in the blood for this reason? I do take in a fair amount of protein (including a whey isolate daily). Also, plenty of eggs. Does dietary protein consumption have any actual affect on HDL's principle protein and/or surface cholesterol esters?

Yes Jack Kronk, it seems that you have low HDL and highish Trigs, I do also think.

Just wanted to comment. I've been a long time low carb person, gluten-free too. I also had my thyroid ablated with RAI many years ago. I have found, as have many low carbers, that my reverse T3 is very high and Free T3 is scraping the bottom or below the range.

Unfortunately this does seem to be a common side-effect of low carb eating. It's even documented in studies on the topic.

We had a low carb eater recently watching his LDL climb to very high levels after he began eating low carb. He started taking cytomel and his LDL is coming down very nicely.

Did he get a sudden onset of hypothyroidism that just coincided with low carb eating? I suppose that's possible, but I do think there's something more going on.

I'm taking Armour thyroid myself, but I still have the tendency to turn T4 into reverse T3 and I suppose that means the Free T3 can't get to the receptors. I'm going to experiment with raising my carbs a little higher and sticking to things like yams and squash for my carbs.

Dear dr. Davis,
I just attended the annual cardiology congress of the European Society of Cardiology. Amongst others, the new guidelines on dyslipidemia were presented and I had the opportunity to ask the working group the question you mention above in your first of opportunities : What about measuring lipids during an ongoing substantial weight loss? The were not able to give me a proper answer.
Do you have any scientific references saying that weight loss induce a temporary dyslipidemia or is it based on your experience?
I would be most thankful for your comment on this.
Best regards
Espen Rostrup, MD, PhD-fellow
Bergen, Norway

Dr. Rostrup--

Unfortunately, I know of no published data documenting this effect. However, I have seen it hundreds of times. It is, in fact, quite predictable: drop in HDL, rise in triglycerides, variable small LDL effects, increased blood glucose. It all subsides and improves over time.

It would indeed be an interesting study to chronicle the changes serially in a small number of people.

I am also seeing a heck of a lot of omega-6 intake there.  Also, the healthfulness of monounsaturated fats is a bit overstated.  I've heard of studies where they had 3 groups of people.  One got their normal saturated fat, one group replaced the saturated fat with olive oil and the third group replaced the sat-fat with corn oil.  The corn oil eaters did the worst in health outcomes, but the olive oil group wasn't great either--both groups that replaced the sat-fat did more poorly.  I've heard of other studies where lard was compared with olive oil and the lard-eaters turned out better.  Bottom line, the human body seems to like saturated fat best.  (Lard is not as saturated as butter, but it is more saturated than olive oil.)  If I were in a position to make medical recommendations (I'm not), I'd tell someone like this to ixnay on the plant oils for a while and see what happens.

It should be noted that one of the more dubious selling points of grass-finished meat is that it is lower in saturated fat.  To me, this is not a selling point.  If this person were only getting PUFAs from their grass-finished meat it would be one thing--at least then it'd be closer to a 1:1 omega-6/omega-3 ratio.  But that's not what's going on here.  If they were just eating the fish they might still be OK (depends on the fish--cold-water is better).  But they're adding in walnut oil and chicken consumption and those are going to add more omega-6, even if the chicken's pastured.

I'm curious what this person's inflammation markers are.  If they're off the map the LDL may still be high because the body's trying to repair the inflammation.  That would explain the low HDL too; LDL takes cholesterol out to the body from the liver, and HDL returns it to the liver.  If the cholesterol is *needed* elsewhere in the body then of course it won't be returned to the liver.

Even if inflammation markers are normal, this person's diet may not be meeting their needs for saturated fats in the cell membranes, which may mean they need more cholesterol in their cell membranes to try to make up the deficit.  Not an ideal situation.

Get the PUFA reduced, get the inflammation down if any, see what the lipids do and then we can talk about weird genes.  Absent the necessary DNA profile we really don't know, anyway.

"just eating the fish" = in addition to the pastured beef.  I would not drop beef in favor of fish, there's too much good nutrition a person would be giving up, but fish in addition to beef's not bad.  Chicken used to be a luxury food, you had it on Sundays if then.  Best that it's relegated to that role again.  The white meat is too dry and the dark meat's rife with PUFAs.  Other fowl are not much better.  A foray into the USDA's nutritional database is an eye-opener.

[...] Genetics: Dr. Davis has argued that some combinations of ApoE alleles may make a  person “unable to deal with fats and dietary cholesterol.” [...]