Overweight, hungry, diabetic, and fat-free

Let me tell you about my low-fat experience from 20 years ago.

At the time, I was living in Cleveland, Ohio, and served on the faculty at a large metropolitan university-affiliated hospital, supervising fellows-in-training and developing high-tech cath lab procedures like directional athererectomy and excimer laser coronary angioplasty. (Yes, another life.)

I was concerned about personal heart disease risk, though I knew next to nothing about lipids and coronary risk prediction outside of the little I learned in training and what the drug industry promoted.

I heard Dr. Dean Ornish talk while attending the American College of Cardiology meetings in Atlanta. Dr. Ornish spoke persuasively about the dangers of fat in the diet and how he "reversed" coronary disease using a low-fat, no added oils, no meat, vegetarian diet that included plenty of whole grains. So I thought I'd give it a try.

I eliminated all oils; I removed all meat, eggs, and fish from my diet. I shunned all nuts. I ate only low-fat products like low-fat yogurt and cottage cheese; and focused on vegetables, fruit, and whole grains. Beans and brown or wild rice were a frequent staple. I loved oatmeal cookies--low-fat, of course!

After one year of this low-fat program, I had gained a total of 31 lbs, going from 155 lbs to 186 lbs. I reassessed some basic labs:

HDL 28 mg/dl
Triglycerides 336 mg/dl
Blood sugar 151 mg/dl (fasting)


I became a diabetic. All through this time, I was also jogging. I ran on the beautiful paths along the Chagrin River in suburban Cleveland for miles north and south. I ran 5 miles per day most days of the week.

It was diabetes that hit me alongside the head: I was eating low-fat meticulously, exercising more than 90% of the population, yet I got fat and diabetic!

I have since changed course in diet. Last time I checked, my lipid values on NO statin agent:

HDL 67 mg/dl
Triglycerides 57 mg/dl
Blood sugar 91 mg/dl

That was my lesson that fat restriction is a destructive, misguided notion. The data since then have confirmed that restricting total fat is unnecessary, even undesirable, when fat calories are replaced by carbohydrate calories.

This is your brain on wheat

Here's just a smattering of the studies performed over the past 30 years on the psychological effects of wheat consumption.

Oddly, this never makes the popular press. But wheat underlies schizophrenia, bipolar illness, behavioral outbursts in autism, Huntington's disease, and attention deficit hyperactivity disorder (ADHD).

The relationship is especially compelling with schizophrenia:

Opioid peptides derived from food proteins: The exorphins.
Zioudrou C et al 1979
"Wheat gluten has been implicated by Dohan and his colleagues in the etiology of schizophrenia and supporting evidence has been provided by others. Our experiments provide a plausible biochemical mechanism for such a role, in the demonstration of the conversion of gluten into peptides with potential central nerovus system actions."


Wheat gluten as a pathogenic factor in schizophrenia
Singh MM et al 1976
"Schizophrenics maintained on a cereal grain-free and milk-free diet and receiving optimal treatment with neuropleptics showed an interruption or reversal of their therapeutic progress during a period of "blind" wheat gluten challenge. The exacerbation of the disease process was not due to variations in neuroleptic doses. After termination of the gluten challenge, the course of improvement was reinstated. The observed effects seemed to be due to a primary schizophrenia-promoting effect of wheat gluten."


Demonstration of high opioid-like activity in isolated peptides from wheat gluten hydrolysates
Huebner FR et al 1984


Is schizophrenia rare if grain is rare?
Dohan FC et al 1984
"Epidemiologic studies demonstrated a strong, dose-dependent relationship between grain intake and the occurrence of schizophrenia."

Small LDL: Perfect index of carbohydrate intake

Measuring the number of small LDL particles is the best index of carbohydrate intake I know of, better than even blood sugar and triglycerides.

In other words, increase carbohydrate intake and small LDL particles increase. Decrease carbohydrates and small LDL particles decrease.

Why?

Carbohydrates increase small LDL via a multistep process:

First step: Increased fatty acid and apoprotein B production in the liver, which leads to increased VLDL production. (Apoprotein B is the principal protein of VLDL and LDL)

Second step: Greater VLDL availability causes triglyceride-rich VLDL to interact with other particles, namely LDL and HDL, enriching them in triglycerides (via the action of cholesteryl-ester transfer protein, or CETP). Much VLDL is converted to LDL.

Third step: Triglyceride-rich LDL is "remodeled" by enzymes like hepatic lipase, which create small LDL.


Carbohydrates, especially if they contain fructose, also prolong the period of time that triglyceride-rich VLDL particles persist in the blood, allowing more time for VLDL to interact with LDL.

Many people are confused by this. "You mean to tell me that reducing carbohydrates reduces LDL cholesterol?" Yes, absolutely. While the world talks about cutting saturated fats and taking statin drugs, cutting carbohydrates, especially wheat (the most offensive of all), cornstarch, and sugars, is the real key to dropping LDL.

However, the effect will not be fully evident if you just look at the crude conventional calculated (Friedewald) LDL cholesterol. This is because restricting carbohydrates not only reduces small LDL, it also increases LDL particle size. This make the calculated Friedewald go up, or it blunts its decrease. Conventional calculated LDL will therefore either underestimate or even conceal the real LDL-reducing effect.

The reduction in LDL is readily apparent if you look at the superior measures, LDL particle number (by NMR) or apoprotein B. Dramatic reductions will be apparent with a reduction in carbohydrates.

Small LDL therefore serves as a sensitive index of carbohydrate intake, one that responds literally within hours of a change in food choices. Anyone following the crude Friedewald calculated LDL will likely not see this. This includes the thousands of clinical studies that rely on this unreliable measure and come to the conclusion that a low-fat diet reduces LDL cholesterol.

Fat "conditioning"

Here's a great study from the prolific laboratory of Dr. Jeff Volek from the University of Connecticut. (Full text here.)


http://jn.nutrition.org/cgi/content/full/134/4/880

Video Teleconference with Dr. William Davis


Dr. Davis is available for personal
one-on-one video teleconferencing

to discuss your heart health issues.


You can obtain Dr. Davis' expertise on issues important to your health, including:

Lipoprotein assessment

Heart scans and coronary calcium scores

Diet and nutrition

Weight loss

Vitamin D supplementation for optimal health

Proper use of omega-3 fatty acids/fish oil



Each personalized session is 30 minutes long and by appointment only. To arrange for a Video Teleconference, go to our Contact Page and specify Video Teleconference in your e-mail. We will contact you as soon as possible on how to arrange the teleconference.


The cost for each 30-minute session is $375, payable in advance. 30-minute follow-up sessions are $275.

(Track Your Plaque Members: Our Member cost is $300 for a 30-minute session; 30-minute follow-up sessions are $200.)

After the completion of your Video Teleconference session, a summary of the important issues discussed will be sent to you.

The Video Teleconference is not meant to replace the opinion of your doctor, nor diagnose or treat any condition. It is simply meant to provide additional discussion about your health issues that should be discussed further with your healthcare provider. Prescriptions cannot be provided.

Note: For an optimal experience, you will need a computer equipped with a microphone and video camera. (Video camera is optional; you will be able to see Dr. Davis, but he will not be able to see you if you lack a camera.)

We use Skype for video teleconferencing. If you do not have Skype or are unfamiliar with this service, our staff will walk you through the few steps required.

Track Your Plaque challenges

Of all the various factors we correct in the Track Your Plaque program in the name of achieving reversal of coronary plaque, there are two factors that are proving to be our greatest challenges:

1) Genetic small LDL

2) Lipoprotein(a)

More and more people are enjoying at least marked slowing, if not zero change or reduction, in heart scan scores following the Track Your Plaque program. We achieve this by correcting a number of factors. Some factors, like vitamin D deficiency, are easily corrected to perfection--supplement sufficient vitamin D to achieve a blood level of 25-hydroxy vitamin D of 60-70 ng/ml. Correcting standard lipid values--LDL cholesterol, HDL cholesterol, and triglycerides--child's play, even to our strict targets of 60-60-60.

However, what I call "genetic small LDL" and a subset of lipoprotein(a) are proving to be the most resistant of all.

Let's first consider genetic small LDL. Small LDL is generally the pattern of the carbohydrate-ingesting, overweight person. It has exploded in severity over the past decade due to overconsumption of carbohydrates due to the ridiculous low-fat notion. Reduce or eliminate carbohydrates, especially wheat, which permits weight loss, and small LDL drops like a stone. But there is a unique subset of people who express the small LDL pattern who start at or near ideal weight. Take Chad, for instance. At 6' 2" and 152 lbs and BMI of 19.6, there's no way excess weight could be triggering his small LDL. Yet he starts with 100% small LDL particles. All efforts to reduce small LDL, such as wheat, cornstarch, and sugar elimination; niacin; vitamin D normalization; thyroid normalization; and several supplements that yield variable effects, such as phosphatidylcholine, all leave Chad with more than 90% small LDL.

Lipoprotein(a) is a bit different. Over the past 5 years, our choices in ways to reduce Lp(a) expression have improved dramatically. Beyond niacin, we now have high-dose EPA + DHA, thyroid normalization that includes use of T3, and hormonal manipulation. In the Track Your Plaque experience, approximately 70% of people with Lp(a) respond with a reduction in Lp(a). (In fact, the 4 out of the 5 record holders for reduction of heart scan scores have Lp(a) that was successfully treated.) But about 30% of people with Lp(a) prove resistant to all these treatments--they begin with a Lp(a) of, say, 260 nmol/L and, despite niacin, high-dose EPA + DHA, and various hormones, stay at 260 nmol/L. It can be frustrating and frightening.

So these are the two true problem areas for the Track Your Plaque program, genetic small LDL and a subset of Lp(a).

We are actively searching for better options for these two problem areas. Given the collective exploration and wisdom that develops from such collaborative efforts as the Track Your Plaque Forum, I am optimistic that we will have better answers for these two stumbling blocks to plaque reversal in the future.

I'll supply the tar if you supply the feathers

The results of the latest Heart Scan Blog poll are in.


DIRECT-TO-CONSUMER PHARMACEUTICAL ADVERTISING HAS:

Increased public awareness of medical conditions and their treatment
19 (11%)

Has had little overall effect on health and healthcare
29 (18%)

Needlessly increased healthcare costs
81 (50%)

Further empowered the revenue-obsessed pharmaceutical industry
130 (81%)


Clearly, there's a lot of negative sentiment against direct-to-consumer (DTC) drug advertising.

It looks as if a small minority believe that good has come from DTC advertising, judging by the meager 11% who voted for increased awareness. In fact, the poll results are heavily weighed towards the negative: 50% voted for "needlessly increased healthcare costs," while an astounding 81% voted for "empowered the revenue-obsessed pharmaceutical industry."

It is, indeed, an odd situation: Pharmaceutical agents available only by prescription being hyped directly to the consumer.

Personally, I would vote for choices 1,3, and 4. While awareness has increased, it has come with a hefty price, not all of it well spent. I believe the pharmaceutical industry still adheres to the rule that, for every $1 spent on advertising, $4 is made in revenue. They are, in effect, printing money.

What goes up can't come down

According to conventional wisdom, heart scan scores cannot be reduced.

In other words, say you begin with a heart scan score of 300. Conventional wisdom says you should take aspirin and a statin drug, eat a low-fat "heart healthy" diet, and take high blood pressure medications, if necessary.

If your heart scan score goes up in a year or two, especially at an annual rate of 20% or more, then you are at very high risk for heart attack. If the heart scan score stays the same, then your risk is much reduced. These observations are well-established.

But more than 99% of physicians will tell you that reducing your heart scan score is impossible. Don't even try: Heart scan scores can go up, but they can't go down.

Baloney. Heart scan scores can indeed go down. And they can go down dramatically.

It is true that, following conventional advice like taking a statin drug, following a low-fat diet, and taking aspirin will fail to reduce your heart scan score. A more rational approach that 1) identifies all causes of coronary plaque, 2) corrects all causes while including crucial strategies like omega-3 fatty acid supplementation, vitamin D supplementation, and thyroid function normalization, is far more likely to yield a halt or reduction in score.

While not everybody who undertakes the Track Your Plaque program will succeed in reducing their heart scan score, a growing number are enjoying success.

A small portion of our experience was documented this past summer. (I collected and analyzed the data with the help of Rush University nutrition scientist, Dr. Susie Rockway, and statistician, Dr. Mary Kwasny.)


Effect of a combined therapeutic approach of intensive lipid management, omega-3 fatty acid supplementation, and increased serum 25 (OH) vitamin D on coronary calcium scores in asymptomatic adults.

Davis W, Rockway S, Kwasny M.

The impact of intensive lipid management, omega-3 fatty acid, and vitamin D3 supplementation on atherosclerotic plaque was assessed through serial computed tomography coronary calcium scoring (CCS). Low-density lipoprotein cholesterol reduction with statin therapy has not been shown to reduce or slow progression of serial CCS in several recent studies, casting doubt on the usefulness of this approach for tracking atherosclerotic progression. In an open-label study, 45 male and female subjects with CCS of > or = 50 without symptoms of heart disease were treated with statin therapy, niacin, and omega-3 fatty acid supplementation to achieve low-density lipoprotein cholesterol and triglycerides < or = 60 mg/dL; high-density lipoprotein > or = 60 mg/dL; and vitamin D3 supplementation to achieve serum levels of > or = 50 ng/mL 25(OH) vitamin D, in addition to diet advice. Lipid profiles of subjects were significantly changed as follows: total cholesterol -24%, low-density lipoprotein -41%; triglycerides -42%, high-density lipoprotein +19%, and mean serum 25(OH) vitamin D levels +83%. After a mean of 18 months, 20 subjects experienced decrease in CCS with mean change of -14.5% (range 0% to -64%); 22 subjects experienced no change or slow annual rate of CCS increase of +12% (range 1%-29%). Only 3 subjects experienced annual CCS progression exceeding 29% (44%-71%). Despite wide variation in response, substantial reduction of CCS was achieved in 44% of subjects and slowed plaque growth in 49% of the subjects applying a broad treatment program.

Gretchen's postprandial diet experiment

Gretchen sent me the results of a little experiment she ran on herself. She measured blood glucose and triglycerides after 1) a low-fat diet and 2) a low-carb diet.









Gretchen describes her experience:

Several years ago I received a windfall of triglyceride strips that would expire in a week or so. I hated to waste them, so I decided to use them to test my triglyceride and BG responses to two different diets: low carb and low fat.

The first day I followed a low-fat diet. For breakfast I ate a lot of carbohydrate, including 1 oz of spaghetti cooked al dente and ¾ cup of white rice. For the rest of the day I ate less carbohydrate but continued to eat low fat.

The second day I followed a low-carb diet. For breakfast I ate a lot of fat, including a sausage, mushrooms fried in butter, 2 slices of bacon, and ¼ cup of the creamy topping of whole-milk yogurt. For the rest of the day I ate less fat, especially less saturated fat, but continued to eat low carb.

Both days I measured both BG and triglyceride levels every hour until I went to bed. On the low-carb day I had 3 meals. On the low-fat day, I was constantly hungry, had 4 meals, and kept snacking.

You can see the results in Figure 1. On the low-fat diet, after a “healthy” low-fat breakfast of low-glycemic pasta with low-fat sauce, my BG levels shot up to over 200 mg/dL and took more than 6 hours to come down. My triglycerides, however, remained low, and at first I thought perhaps the low-fat diet might be better overall. However, after about 6 hours, the triglyceride levels started to increase steadily, and by the next morning, they were higher than they had been the day before.
On the low-carb diet, my BG levels stayed low all day. However, after meals, the triglyceride levels skyrocketed. After meals they came down, and by the next morning they were lower than they had been the day before.

As I interpret these results, the high triglyceride levels after eating the high-fat meals represent chylomicrons, the lipoproteins that transport fat from your meals to the cells of your body. The high triglyceride levels the morning after eating the low-fat meals represent very low density lipoprotein, which takes the cholesterol your liver synthesizes when your intake of dietary cholesterol is low and distributes it to cells that need it, or again, to the fat for storage.

There are several interesting factors to consider here. First, when you have a lipid test done at the lab, it’s usually done fasting, which means first thing in the morning after not eating for 8 to 12 hours. It tells you nothing about what your triglyceride levels were all day.

Second, the low-carb diet resulted in lower fasting triglyceride levels, but much higher postprandial triglyceride levels. Which are more dangerous? I’m afraid I don’t know. You should also note that the high-fat, low-carb breakfast was extremely high in fat, including saturated fat. I don’t normally eat that much fat but wanted to test extremes.

Third, although the low-fat diet didn’t produce the very high postprandial triglyceride levels that the high-fat diet did, it produced extremely high BG levels that persisted for 6 hours. Some people think that it’s oxidized and glycated lipids that are the dangerous ones, so high BG levels and normal triglyceride levels might be more dangerous than very high triglyceride levels and normal BG levels. Note that high BG levels also contribute to oxidation rates.

Fourth, this shows the results of an experiment with a sample size of one. My physiology might not be typical. If you want to know how your own body’s lipids respond to different types of diets, you should get a lipid meter and test yourself. Unfortunately, your insurance is unlikely to want to pay for this, so it will be an expensive experiment.

The main point of this is that the results of different diets are complex. We have to eat. And what we eat can affect many different systems in our bodies. Finding the ideal diet that matches our own physiology and results in the best lipid levels as well as BG levels is a real challenge.



This was a lot of effort for one person. Thanks to Gretchen for sharing her interesting experience.

Gretchen makes a crucial point: Some of the effects of diet changes evolve over time, much as triglyceride levels changed substantially for her on the day following her experiment. Wouldn't it be interesting to see how postprandial patterns develop over time if levels were observed sequentially, day after day?

The stark contrast in blood sugars is impressive--Low-carb clearly has the advantage here. Are there manipulations in diet composition in low-carb meals that we can make to blunt the early (3-6 hour) postprandial lipoprotein (triglyceride) peak? That's a topic we will consider in future.

More of Gretchen's thoughts can be found at:

http://wildlyfluctuating.blogspot.com
http://www.healthcentral.com/diabetes/c/5068

After-eating effects: Carbohydrates vs. fats

In the ongoing debate over whether it's fat or carbohydrate restriction that leads to weight loss and health, here's another study from the Oxford group examining the postprandial (after-eating) effects of a low-fat vs. low-carbohydrate diet. (Roberts R et al, 2008; full-text here.)

High-carbohydrate was defined as 15% protein; 10% fat; 75% carbohydrate (by calories), with starch:sugar 70:30.

High-fat was defined as 15% protein; 40% fat; 45% carbohydrate, with starch:sugar 70:30. (Yes, I know. By our standards, the "high-fat" diet was moderate-fat, moderate-carbohydrate--too high in carbohydrates.)

Blood was drawn over 6 hours following the test meal.




Roberts R et al. Am J Clin Nutr 2008

The upper left graph is the one of interest. Note that, after the high-carbohydrate diet (solid circles), triglyceride levels are twice that occurring after the high-fat diet (open circles). Triglycerides are a surrogate for chylomicron and VLDL postprandial lipoproteins; thus, after the high-carbohydrate diet, postprandial particles are present at much higher levels than after the high-fat diet. (It would have been interesting to have seen a true low-carbohydrate diet for comparison.) Also note that, not only are triglyceride levels higher after high-carbohydrate intake, but they remain sustained at the 6-hour mark, unlike the sharper decline after high-fat.

It's counterintuitive: Postprandial lipoproteins, you'd think, would be plentiful after ingesting a large quantity of fat, since fat must be absorbed via chylomicrons into the bloodstream. But it's carbohydrates (and obesity, a huge effect; more on that in future) that figure most prominently in determining the pattern and magnitude of postprandial triglycerides and lipoproteins. Much of this effect develops by way of de novo lipogenesis, the generation of new lipoproteins like VLDL after carbohydrate ingestion.

We also see this in our Track Your Plaque experience. Rather than formal postprandial meal-testing, we use intermediate-density lipoprotein (IDL) as our surrogate for postprandial measures. A low-carbohydrate diet reduces IDL dramatically, as do omega-3 fatty acids from fish oil.
Handy dandy carb index

Handy dandy carb index

There are a number of ways to gauge your dietary carbohydrate exposure and its physiologic consequences.

One of my favorite ways is to do fingerstick blood sugars for a one-hour postprandial glucose. I like this because it provides real-time feedback on the glucose consequences of your last meal. This can pinpoint problem areas in your diet.

Another way is to measure small LDL particles. Because small LDL particles are created through a cascade that begins with carbohydrate consumption, measuring them provides an index of both carbohydrate exposure and sensitivity. Drawback: Getting access to the test.

For many people, the most practical and widely available gauge of carbohydrate intake and sensitivity is your hemoglobin A1c, or HbA1c.

HbA1c reflects the previous 60 to 90 days blood sugar fluctuations, since hemoglobin is irreversibly glycated by blood glucose. (Glycation is also the phenomenon responsible for formation of cataracts from glycation of lens proteins, kidney disease, arthritis from glycation of cartilage proteins, atherosclerosis from LDL glycation and components of the arterial wall, and many other conditions.)

HbA1c of a primitive hunter-gatherer foraging for leaves, roots, berries, and hunting for elk, ibex, wild boar, reptiles, and fish: 4.5% or less.

HbA1c of an average American: 5.2% (In the population I see, however, it is typically 5.6%, with many 6.0% and higher.)

HbA1c of diabetics: 6.5% or greater.

Don't be falsely reassured by not having a HbA1c that meets "official" criteria for diabetes. A HbA1c of 5.8%, for example, means that many of the complications suffered by diabetics--kidney disease, heightened risk for atherosclerosis, osteoarthritis, cataracts--are experienced at nearly the same rate as diabetics.

With our wheat-free, cornstarch-free, sugar-free diet, we have been aiming to reduce HbA1c to 4.8% or less, much as if you spent your days tracking wild boar.

Comments (21) -

  • Anonymous

    3/25/2011 3:19:26 AM |

    Dr. Davis,

    Can someone have a good HbA1c but still have an undesirable amount of small particle LDL? ..Like perhaps someone with FHC that has their LDL particles floating around longer in the bloodstream and hence exposed longer to oxidants.

    Thank you.

    John M.

  • Tyler

    3/25/2011 3:51:56 AM |

    I love your blog but I have to clarify on this point. Check out the post by chris kresser: http://chriskresser.com/blog/why-hemoglobin-a1c-is-not-a-reliable-marker/

    a1c is not reliable for many people because of the variation in RBC life length. healthy people's red blood cells may live as over 4 months whereas diabetic's live only as 60 days. This results in vast discrepancies.

    For example my fasting BG averages 77 and postprandial peak is 85-90, but my hemoglobin A1c is 5.7

    This doesn't make sense unless you account for differences in RBC lifetime.

  • Kris @ Health Blog

    3/25/2011 11:45:32 AM |

    I'm wondering what your opinion is of glycation and aging.

    I've been reading that a major part of the aging process might be caused by glycation of proteins in the body, mostly caused by elevated blood sugar.

    Do you believe that practically, one could expect a longer life expectancy to correlate with lower blood sugar levels?

  • Larry

    3/25/2011 12:09:46 PM |

    The other day on the tv show, "The Doctors", they profiled a young woman concerned about her FBG.
    She said that Diabetes ran in her family.
    They did a bloodtest and announced that her FBG was 111.
    The scary part was when they told her that reading was okay.
    With that FBG, one can assume that everytime she eats, her post-prandial FBG is heading into dangerous territory.
    But they told her not to worry.
    She was right about her concern...as Diabetes will continue to run in her family.
    Especially with that advice.

  • Jonathan

    3/25/2011 2:44:03 PM |

    I found Walmart carries a Bayer at home A1c test kit that gives results in 5 minutes.  It came with two test cartridges so I was able to take one when I started lowcarb and another one 4 months later to see how much it came down.  (I came down from 8.3 to 5.2 in 4 months)

  • revelo

    3/25/2011 4:45:55 PM |

    What is HbA1c for those long-lived okinawans with their rice-based diet, or those long-lived cretans with their wheat-based diet?

    Wouldn't a lean healthy body (especially if there is occasional fasting) eventually clean up glycated and otherwise damaged proteins?

  • Might-o'chondri-AL

    3/25/2011 6:22:18 PM |

    Glycation picks on the amino acid valine "wing" on the molecule of haemoglobin's B-chain portion. Aldehydes, both glucose aldehydes and non-glucose ones can become bound to that valine.

    This can occur several ways. Glucose oxidation yields a byproduct, called gly-oxal; this is what most people monitor. In the glyco-lytic pathway called Embden-Meyerhof triose-phosphate drives gly-oxal into the molecule methyl-glyoxal (MG).

    Type 1 diabetics have circulating methyl-glyoxal (MG) levels that are +/- 6 times greater normal. MG is a glycation end product.

    Tyler's comment links to a discussion of fructosamine monitoring. This is from a non-enzyme driven reaction, called Amadori, where fructo-selysine and the fructos-amine 3 kinase cascade generates 3 De-oxy-glucos-ane (3DG); another glycation end product.

    Enzymatic glycation occurs in pathological states. Macrophage activity spins off  the enzyme myelo-peroxidase; this generates hypo-chlorite. Hypo-chlorite pulls in the amino acid serine and then together they cause the formation of certain advanced glycation end-products; namely glyco-aldehyde and glycer-aldehyde.

    Yet another non-enzyme chain of events can generate advanced glycation end products. This is when the molecule per-oxy-nitrite (ONOO-)gets stalled inside the cell and it induces the formation of gly-oxal/gluco-sone/aldehyde molecules that can contribute to glycation.

    ONOO- normally is part of healthy cell signaling. When a metabolic processes is under sustained "stress" it (ONOO-) can't shift the cell function over to what it (the cell) needs to do (in order to adapt and cope). Instead of briefly signalling, signing off and going away ONOO-
    lingers in the cell; a situation that may also be related to ageing.

  • Anonymous

    3/25/2011 7:10:22 PM |

    I wonder if Dr. Davis can comment on situations where carb intake is reasonable and the patient has a decent HBA1c, yet still has higher than normal triglycerides and small LDL?

    My own HBA1c has been in the 4.5-4.6 range, yet my trigs hover around 140-150, and I still have more small LDL than I'd like.

    If restricting carbs doesn't work, D levels normalized, etc. what else could be the cause of higher than optimal triglycerides?

    I know people with HBA1cs in the 5.4+ range, eat many more carbs than I do, yet still have lower trig numbers.

  • Might-o'chondri-AL

    3/25/2011 8:58:10 PM |

    Hi Revelo,
    Vitis vinifera leaf inhibits advanced glycation end product (AGE) formation. That is what many cultures, like Crete, eat wrapped around their cereal grain; we call it Grape Leaves in English (ex: stuffed grape leaves, a.k.a. Dolma in Greek).

    Japan researchers (2009?) took 1 kilogram of dried grape leaves in 20 liters of water and stirred it for 3 hours at 80*Celcius. They administered the decoction in various dosages and found it can reduce the AGE of 3DG (3 de-oxy-gluco-sone) and also a marker of AGE in kidney disease, pentosidine, down to 1/5th the level from that study's AGE control levels.

    The same study experimented with Anthemis nobilis using the same extraction technique detailed above. They propose the active ingredient responsible for the AGE inhibition is the compound called chamaemoliside.

    Chamomile is the name of this plant in English; I suspect it is drunk as a tea in Crete. In the range of AGE inhibitors that they tested Chamomile was better acting than any other; grape leaves efficacy came in second.

    Plants studied that inhibit AGE forming, in no particular order of effectiveness may interest you. These are: Crataegus oxyacantha (English = Hawthorn berry), Houttuynia cordata (English = Chameleon plant) and Astragalus membranaceous (English = Astragalus). Chameleon plant is a regular condiment used in Vietnamese and some south-east asian food; it smells kind of "fishy".

  • revelo

    3/25/2011 9:02:19 PM |

    According to Steven Gundry MD, it is MEAT which is the primary cause of AGE's. (He doesn't cite any references for this in his "Diet Evolution" book.) He recommends Atkin's style low-carb/high-protein to lose weight, then low-fat (15% of calories from fat) as the maintenance diet. He is not too keen on grains, tubers or fruit, but rather emphasizes green vegetables.

  • Tyler

    3/25/2011 9:50:41 PM |

    Thanks for the nice explanations Might-o'chondri-AL

  • Might-o'chondri-AL

    3/25/2011 10:46:23 PM |

    Diabetic nephro-pathy (ie: kidney complication), and kidney disease have elevated AGE. These are monitored as pento-sidine, gly-oxal, methyl-gly-oxal and 3 de-oxy-gluco-sane; which the body tries to excrete as carbonyly compounds.

    Carbonyl compounds are hard to get through the kidney filters and cause an increase in uric uremia, which can be toxic. Too many carbonyls can cause, the so called, "carbonyl stress" of diabetic nephro-pathy.

    Diabetic patients' kidneys eventually can't excrete enough sodium (Na); and that contributes to the high blood pressure (hyper-tension) diabetics tend to suffer from.

    Ketones merit mentioning too. One of the markers for AGE in the kidneys is N-carb-oxy-ethl-lysine; which may (or may not) be a side effect of ketones. Type 1 diabetics do show elevated ketone levels incidently.

    I am not able to offer any perspective on ketogenic diets and AGE however. However, vitamin C is known to decrease ketone bodies. (In the previous post, "Battery acid ...", more
    diabetic responses to vitamin C appears among the comments.)

  • Anonymous

    3/26/2011 4:46:17 AM |

    I've been eating low-carb (basically paleo) for the last 4-5 mo and just got my lipid panel results.  They sky-rocketed.

    Cholesterol 300
      
    Triglyceride 150  
        
    HDL          33
        
    LDL             237


    Every number got worse.  The part that really sucks, is that the diet makes me feel great and nearly all my body fat is gone.  I'm 37, 5'11, 180 lbs and probably about 9% body fat.  Now I'm wondering what kind of trade-off I'm making.  Any thoughts, doc?

  • Peter

    3/26/2011 12:55:22 PM |

    Testing different foods one hour after meals, it seems like a good rule of thumb for me is that each ounce of carbs raises my blood sugar about 10 mg,and that the kind of carb doesn't matter nearly as much as the quantity.

  • Might-o'chondri-AL

    3/26/2011 6:31:09 PM |

    Paradoxical low carb yet relatively high HbA1c & higher carb but relatively lower HbA1c is reported by Annon. Doc assuredly deals with cases like these and has to resolve their enigma one by one.  

    The gene HFE (human hemochromatosis protein, nicknamed High Fe  where iron = Fe)can have a variation (reference code = HFE rs1800562). This variation is seen in +/- 5% of Caucasians, but is not found in East Asian nor African genes.

    More hemoglobin is in circulation for those having this HFE genetic variation. In this case, the same amount of blood sugar that can contribute to glycation of hemoglobin has more hemoglobin surfaces to glycate. Think of it as the glycation has to spread itself thin; the dilution of it's effect makes the % of Hb1Ac less (ie: lower Hb1Ac % measured in the blood sample).

    On the other hand, genetic variation rs855791 of the gene TMPRSS6 (trans-membrane protease, serine 6)is implicated in anemia. In these individuals Hb1Ac readings range higher; there is less hemoglobin relative to the glycation potential in their blood stream. Think of it as the relatively low proportion of hemoglobin which has to bear all the glycation burden
    (ie: Hb1Ac % is higher in their blood sample).

    Anemic (hemolytic) tendency is also driven by variation of gene HK1 (hexo-kinase 1). This enzyme modulates how glucose inside the cell goes through  it's processing pathways.

    This gene (HK1) codes for the unique iso-form of erythrocytes; erythrocyte configuration can figure in to low hemoglobin. In other words it is also a factor in high Hb1Ac readings; glycation potential in the blood over burdens the limited amount of hemoglobin around.

  • Dr. William Davis

    3/26/2011 6:34:23 PM |

    In response to several questions about the potential disconnect between small LDL/triglycerides and HbA1c: Yes, there are people in which one measure is more resistant. It varies based on the mix of underlying genetic predispositions, so it's hard to generalize.


    Might-o'-chondri-AL--

    Great discussion. Thanks, as always. You bring an incredibly sophisticated perspective!

  • Dr. William Davis

    3/26/2011 6:35:48 PM |

    Jonathan--

    Spectacular! And within an unusually brief timeline for HbA1c.


    Revelo--

    Might-o'chondri-AL is referring to endogenous glycation. You are citing a discussion about exogenous glycation, two separate phenomena.

  • Might-o'chondri-AL

    3/27/2011 1:31:59 AM |

    Might Jenny's observation and Nigel's study reference be reconciled somewhat ? I'll tag on my disclaimer of being unqualified to judge low carb or specific diets; since I've never struggled with weight or diabetes, and am not a doctor.

    The study Nigel linked was done with all Kuwaiti subjects. In that country co-sanguinity in marriage is practised by +/- 54.3 % of Kuwaitis. And 1 in 5 are reported to be diabetic.

    The data is very admirable; my suggestion is that the data trend may not exactly transfer to a modern Caucasian population; which is essentially interbred from migration and war (rape). This may be why Jenny sees a +/- 6 month plateau among her respondents and the co-sanguine Kuwaitis saw changes continue for a year +.

    Genetic poly-morphisms influence fasting glucose (GCK, G6PC2 and MTNR1B), are implicated in Hb1Ac, triglyceride levels, HDL levels & so on. That said, I personally would try the low carb approach if I was diabetic.

  • Might-o'chondri-AL

    3/27/2011 1:32:47 AM |

    oops posted this in wrong thread

  • Anonymous

    3/27/2011 3:12:44 AM |

    Re: Anonymous with Cholesterol 300,  Triglycerides 150,  HDL 33 ...

    Suggest you try a technique many dieabetics find helpful to understand food consumption influence on their blood sugar profile,"eating to your meter".
    For a few days, record your blood sugar level immediately before eating a "normal" meal, and then after the meal get 1-hour and 2-hour post-meal blood sugar readings. Separate meals by at least 4 hours. Concentrate on monitoring your main meals and ignore snacking for the first go around. Better however, if you can actually avoid all snaking during period of the testing. Also you will want to add to your journal the foods, ammount consumed, and time it was consumed. If post-meal blood sugar values are high, then to determine a pattern folllowing a meal do a series of hourly post-meal readings until you reach 85 mg/dL or so. As a graph, these results should be helpful to you. Expect that the results will be revealing to you with unexpected high blood sugar values even after following a paleo diet. And if so, it does mean that paleo is not for you, only that you need to more discriminating in what and how much you actually consume.

    I would be interested in hearing about your findings. By the way, you did not mention the blood glucose or HbA1c results of your recent lab tests.

    My regards and good luck ... spo

    BTW: practice good technique with the finger sticks. Do a quick but good hand wash using soap and a warm water rinse prior to a stick. Dry hands well. Dont squeeze hard at the site to encourage blood flow. The original stick should be sufficent to raise a drop of blood for the test strip. Using alcohol swabs and changing out lancets is not necessry when only working on youtself. Keep the test strip vial tightly closed other then when removing the current test strip. If you encounter an "extreme" value, retest for confirmation but clean hands again prior to the retest. My experiences regarding unexpected readings seems to usually invovle hand and finger contamination of some form.

    Finally, on Amazon.com I am able to purchase unexpired test strips in 50 strip lots for my old AcuCheK Confort Curve meter for less than $0.16 or so a strip and often with free shipping. You just have to broswe around a bit.

  • Jonathan

    3/30/2011 2:47:32 PM |

    @ Anonymous with 300 TC
    I would say it could possibly be your liver cleaning itself out (it could have been getting fatty).  The higher Trig might be a sign you are getting too many carbs from somewhere (at least till your sugar stores empty some and insulin sensitivity goes back up) but it could be the liver cleaning out as well.  I think HyperLipid posted something about this once.

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