Is there something fishy about fish oil?

To be sure, there's plenty of misinformation out there about fish oil. Take a look at the swill that passes for health information on Woman's Day: On Call with Dr. Sandy: Fish Oil and Mercury:



Reader Question: My doctor recommended that I take a fish oil supplement, but I'm concerned about mercury. Is there any way to tell which brands are lowest in mercury content?



On Call Response: When it comes to OTC supplements, the answer is no. Though most fish oil supplements sold by major brands are probably safe, there's really no way to tell what's in the bottle or how much mercury it might contain.




Perhaps Dr. Sandy should read the many independent analyses performed on nutritional supplement fish oil, including those at Consumer Lab and Consumer Report before she offers her blind criticisms.

Lovaza vs fish oil supplements?

Lovaza is the FDA-approved form of fish oil that is available only by prescription. It contains 842 mg of the omega-3 fatty acids, EPA and DHA, per capsule.

The FDA application for Lovaza is viewable here on the FDA website. Interestingly, while there is plenty of the usual regulatory gobbledy-gook about toxicology, dose escalation, and efficacy in the extensive documentation, there is little said about the issue of contamination.

In other words, critics of nutritional supplement fish oil harp on the possibility of contamination with mercury and pesticide residues, like dioxin and PCBs (polychlorinated biphenyls). Yet there is virtually nothing about these same issues in the FDA application for Lovaza.

Let's take a look at a sample over-the-counter fish oil product. Our friends at PharmaNutrients (a new Track Your Plaque partner for nutritional supplements) have a fish oil product called PharmaNutrients" Cardio. Here's an independent analysis of the Cardio product (per 1000 mg fish oil capsule):

EPA content: 566.1 mg
DHA content: 216.6 mg
(Total EPA + DHA 782.7 mg)

Cardio passed all tests for peroxides, PCBs, dioxin, furans, dioxin-like PCBs, and heavy metals (arsenic, cadmium, lead, mercury) using criteria at least 60% more stringent than European Commission (EC) standards (EC standard <2 picograms/gm for dioxins and furans, PharmaNutrients <1 picograms/gm; EC standard <10 picograms/gm for dioxin-like PCBs, PharmaNutrients <3 picograms/gm). PCBs levels in particular are less than 0.009 ppm, 90% below the industry-wide purity standard of 0.09 ppm. Likewise, mercury is >90% lower than European Commission standards.

In other words, this over-the-counter "pharmaceutical grade" fish oil has virtually nothing but omega-3 fatty acids.

Interestingly, the PharmaNutrients fish oil capsule also contains the third omega-3 fatty acid, docosapentaenoic acid (DPA), a neglected form that some authorities have proposed has superior cardiovascular protective properties over eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). If DPA is included in the analysis, PharmaNutrient's Cardio contains a total of 900 mg omega-3 fatty acids per capsule.

At some point, I'd like to see a head-to-head comparison not just on purity grounds, since I am convinced that high-quality products like Cardio can match or exceed the purity of prescription fish oil, but on efficacy in raising omega-3 blood levels, the omega-3 index. (The omega-3 index is a predictor of heart attack and sudden cardiac death--the higher, the better.) My prediction: High-quality fish oil supplements will match or exceed prescription fish oil.

More on blood sugar

Take any of the following foods:

One chicken breast
Quarter-pound ground beef
6 oz salmon steak
½ cup raw almonds
3 eggs scrambled in olive oil

How much is blood sugar increased by any item in the above list?

If you said virtually zero, you’re correct. Eat any of these foods, regardless of portion size, and blood sugar won’t change substantially. If you started with a blood sugar of, say, 90 mg/dl, 1-2 hours later it would be 90 mg/dl. It might go up or even down a few milligrams, but for all practical purposes it remains substantially unchanged.

How much is blood sugar increased by the foods in this list:

2 slices multigrain bread
1 whole wheat bagel
4 oz high-fiber breakfast cereal
2 whole grain pancakes, 2 oz maple syrup

The foods in this list are a different story from the first. Depending on your body weight, exercise habits, and other factors, a typical blood sugar response in an otherwise healthy non-diabetic person would be 120 mg/dl to 160 mg/dl. In someone with diabetes, it could easily exceed 200 mg/dl.

That isn’t good. Large blood sugar excursions to 140 mg/dl have been clearly associated with greater risk for heart attack, progression to diabetes, inflammatory responses, and other adverse health effects. In fact, blood sugars as low as 100 mg/dl after eating have been associated with increased cardiovascular risk.

Then why are the USDA, American Heart Association, the American Dietetic Association, and the American Diabetes Association telling us to eat more of the foods that shoot blood sugar up to such high levels? “Eat more healthy whole grains”?

To see how much the issue of exaggerated blood sugars after eating applies to you, a simple blood sugar check 1-2 hours after eating can show you. Either your doctor can have the test drawn or you can purchase your own inexpensive glucose meter (e.g., Walmart, Wagreens).

My prediction: You will be very surprised at blood sugar responses after common foods, including “healthy whole grains.” And, by the way, keeping blood sugar excursions to a minimum will facilitate weight loss.

Postprandial blood sugar: Almonds vs. whole wheat bread

Here's my postprandial (after-eating) blood glucose demonstration.



I tested raw almonds vs. 100% whole wheat bread, matched for calories. (Full nutritional composition below.)



Blood sugars:

Raw almonds

Start:

One-hour after eating:





2 slices 100% whole wheat bread

Start:

One-hour after eating:





100% whole wheat bread, 2 large slices

Water (g) 24.69

Energy (kcal) 158

Protein (g) 8.29

Fat, total (g) 2.14

Carbohydrate (g) 26.43

Sugars, total (g) 3.56

Fiber, total dietary (g) 4.4

Cholesterol (mg) 0

Saturated fatty acids, total (g) 0.478

Monounsaturated fatty acids, total (g) 1.022

Polyunsaturated fatty acids, total (g) 0.384





23 almonds, raw



Energy (kcal) 159

Protein (g) 5.86

Fat, total (g) 13.64

Carbohydrate (g) 5.98

Sugars, total (g) 1.07

Fiber, total dietary (g) 3.4

Cholesterol (mg) 0

Saturated fatty acids, total (g) 1.03

Monounsaturated fatty acids, total (g) 8.525

Polyunsaturated fatty acids, total (g) 3.331



To get low-carb right, you need to check blood sugars

Reducing your carbohydrate exposure, particularly to wheat, cornstarch, and sucrose (table sugar), helps with weight loss; reduction of triglycerides, small LDL, and c-reactive protein; increases HDL; reduces blood pressure. There should be no remaining doubt on these effects.

However, I am going to propose that you cannot truly get your low-carb diet right without checking blood sugars. Let me explain.

Carbohydrates are the dominant driver of blood sugar (glucose) after eating. But it's clear that we also obtain some wonderfully healthy nutrients from carbohydrate sources: Think anthocyanins from blueberries and pomegranates, vitamin C from citrus, and soluble fiber from beans. There are many good things in carbohydrate foods.

How do we weigh the need to reduce carbohydrates with their benefits?

Blood sugar after eating ("postprandial") is the best index of carbohydrate metabolism we have (not fasting blood sugar). It also provides an indirect gauge of small LDL. Checking your blood sugar (glucose) has become an easy and relatively inexpensive tool that just about anybody can incorporate into health habits. More often than not, it can also provide you with some unexpected insights about your response to diet.

If you’re not a diabetic, why bother checking blood sugar? New studies have documented the increased likelihood of cardiovascular events with increased postprandial blood sugars well below the ranges regarded as diabetic. A blood sugar level of 140 mg/dl after a meal carries 30-60% increased (relative) risk for heart attack and other events. The increase in risk begins at even lower levels, perhaps 110 mg/dl or lower after-eating.

We use a one-hour after eating blood sugar to gauge the effects of a meal. If, for instance, your dinner of baked chicken, asparagus brushed with olive oil, sauteed mushrooms, mashed potatoes, and a piece of Italian bread yields a one-hour blood sugar of 155 mg/dl, you know that something is wrong. (This is far more common than most people think.)

Doing this myself, I have been shocked at the times I've had an unexpectedly high blood sugar from seemingly "safe' foods, or when a store- or restaurant-bought meal had some concealed source of sugar or carbohydrate. (I recently had a restaurant meal of a turkey burger with cheese, mixed salad with balsamic vinegar dressing, along with a few bites of my wife's veggie omelet. Blood sugar one hour later: 127 mg/dl. I believe sugar added to the salad dressing was the culprit.)

You can now purchase your own blood glucose monitor at stores like Walmart and Walgreens for $10-20. You will also need to purchase the fingerstick lancets and test strips; the test strips are the most costly part of the picture, usually running $0.50 to $1.00 per test strip. But since people without diabetes check their blood sugar only occasionally, the cost of the test strips is, over time, modest. I've had several devices over the years, but my current favorite for ease-of-use is the LifeScan OneTouch UltraMini that cost me $18.99 at Walgreens.

Checking after-meal blood sugars is, in my view, a powerful means of managing diet when reducing carbohydrate exposure is your goal. It provides immediate feedback on the carbohydrate aspect of your diet, allowing you to adjust and tweak carbohydrate intake to your individual metabolism.

Food sources of vitamin K2: Reprint

For some reason, my December, 2007, Heart Scan Blog post, Food sources of vitamin K2, has been receiving a lot of traffic.

I therefore reprint the vitamin K2 post below.





Vitamin K2 is emerging as an exciting player in the control and possible regression of coronary atherosclerotic plaque. Only about 10% of dietary vitamin K intake is in the K2 form, the other 90% being the more common K1.

The ideal source of K2 is natto, the unpalatable, gooey, slimy mass of fermented soybeans that Japanese eat and has been held responsible for substantial decreases in osteoporosis and bone fractures of aging. Natto has an ammonia-like bouquet, in addition to its phlegmy consistency that makes it virtually inedible to anyone but native Japanese.

I say that the conversation on vitamin K2 is emerging because of a number of uncertainties: What form of vitamin K2 is best (so-called MK-4 vs. MK7 vs. MK-9, all of which vary in structure and duration of action in human blood)? What dose is required for bone benefits vs. other benefits outside of bone health? Why would humans have developed a need for a nutrient that is created through fermentation with only small quantities in meats and other non-fermented foods?

Much of the developing research on vit K2 is coming from the laboratories of Drs. Vermeer, Geleijnse, and Schurgers at the University of Maastricht in the Netherlands, along with several laboratories in Japan, the champions of K2.

MK-7 and MK-8,9,10 come from bacterial fermentation, whether in natto, cheese, or in your intestinal tract; MK-4 is naturally synthesized by animals from vitamin K1. While natto is the richest source of the MK-7 form, egg yolks and fermented cheeses are the richest sources of the MK-4 form.

Chicken contains about 8 mcg MK-4 per 3 1/2 oz serving; beef contains about 1 mcg. Egg yolks contain 31 mcg MK-4 per 3 1/2 oz serving (app. 6 raw yolks). Hard cheeses contain about 5 mcg MK-4 per 3 1/2 oz serving, about 70 mcg of MK-8,9; soft cheeses contain about 30% less. Natto contains about 1000 mcg of MK-7, 84 mcg MK-8, and no MK-4 per 3 1/2 oz serving.















Feta cheese

Thanks to the research efforts of the Dutch and Japanese groups, several phenomena surrounding vitamin K2 are clear, even well-established fact:

--Vitamin K2 supplementation (via frequent natto consumption or pharmaceutical doses of K2) substantially improves bone health. While K2 by itself exerts significant bone density/strength increasing properties in dozens of studies, when combined with other bone health-promoting agents (e.g., vitamin D3, prescription drugs like Fosamax and calcitonin), an exaggerated synergy of bone health-promoting effects develop.



--The MK-4 form of vitamin K2 is short-lived, lasting only 3-4 hours in the body. The MK-7 form, in contrast, the form in natto, lasts several days. MK-7 and MK-8-10 are extremely well absorbed, virtually complete.

--Bone health benefits have been shown for both the MK-7 and MK-4 forms.

--Coumadin (warfarin) blocks all forms of vitamin K.





Interestingly, farm-raised meats and eggs do not differ from factory farm-raised foods in K2 content. (But please do not regard this as an endorsement of factory farm foods.)

Another interesting fact: Since mammals synthesize a small quantity of Vit K2 forms from vitamin K1, then eating lots of green vegetables should provide substrate for some quantity of K2 conversion. However, work by Schurgers et al have shown that K1 absorption is poor, no more than 10%, but increases significantly when vegetables are eaten in the presence of oils. (Thus arguing that oils are meant to be part of the human diet. Does your olive oil or oil-based salad dressing represent fulfillment of some subconscious biologic imperative?)

If we believe the data of the Rotterdam Heart Study, then a threshold of 32.7 micrograms of K2 from cheese yields the reduction in cardiovascular events and aortic calcification.

It's all very, very interesting. My prediction is that abnormal (pathologic) calcium deposition will prove to be a basic process that parallels atherosclerotic plaque growth, and that manipulation of phenomena that impact on calcium depostion also impact on atherosclerotic plaque growth. Vitamins D3 and K2 provide potential potent means of at least partially normalizing these processes.

As the data matures, I am going to enjoy my gouda, Emmenthaler, Gruyere, and feta cheeses, along with a few egg yolks. I'm going to be certain to include healthy oils like olive and canola with my vegetables.


All images courtesy Wikipedia.

Copyright 2007 William Davis, MD

Family lessons

Lou was recovering from his 3rd bypass operation. This third go-round left him weaker, slower, less quick on the rebound. In fact, he was lucky to have survived.

At 71 years old, Lou went a good 15 years since his second bypass, another 10 years prior to his first bypass at age 46.

In the days immediately following Lou's bypass, I had a chance to talk to his son, who stayed at his Dad's bedside while Lou struggled through post-op recovery.

"Did your Dad tell you about why this has happened, what caused his heart disease?" I asked.

"Sort of. He just said I should get checked," Lou's son, Aaron, replied.

"Did he mention the lipoprotein(a) pattern he has?"

"No. He never mentioned anything like that. He just said to get checked."

That's how it gets played out more often than not: Mom or Dad has a heart attack, stents, or (3rd) bypass, the children are told to get checked. Getting "checked" assumes that the doctor knows what to check for.

In Lou's case, the reason why he was in the hospital getting his 3rd (and final) bypass was lipoprotein(a), along with genetically-determined small LDL particles, low HDL, a postprandial (after-eating) disorder, hypertension, and borderline diabetes, not to mention vitamin D deficiency, omega-3 fatty acid deficiency, and marginal thyroid function. (Lou, a retired city employee, had showed only marginal interest in correcting these patterns. While he accepted medications, he proved unwilling to engage in the diet and nutritional supplement strategies required to correct his patterns.)

So Lou's 3rd bypass operation provided a moment of reflection for Aaron to ask: "Could I share the fate of my Dad?" With Lou's combination of genetic patterns, there was at least a 75% likelihood that he did. Sadly, going to his doctor would likely yield little more than a cholesterol panel, a question about smoking, and a prescription for Lipitor.

Just getting "checked" would be, more than likely, a recipe for disaster for Aaron: heart disease in his 40s or 50s. That's why you need to take control over this sad state of affairs and ask--no, insist--that an effort be made to determine whether you might share your parents' fate.

Look like Jimmy Stewart


"This diet works great," Don declared. "But I think I've lost too much weight."

At 67 years old and 5 ft. 11 inches, Don began the program weighing 228 lbs (BMI 31.9). Because of high triglycerides, high blood sugar, high c-reactive protein, and excessive small LDL, I instructed Don to eliminate all wheat products from his diet, along with cornstarch and sweets. His intake of lean meats, eggs, vegetables, oils, raw nuts, etc. was unlimited.

Don now weighed 194 lbs, down 34 lbs over 6 months (BMI 27.1). Triglycerides, blood sugar, blood pressure, and well-being had improved dramatically; small LDL, however, had dropped only 30%--still room for improvement.

"My friends say I'm too skinny. They ask if I have cancer!"

I've heard this many times: Someone loses weight in a relatively short period of time and friends and family tell you you're too skinny. "It must be cancer. Nobody loses weight like that."

Unfortunately, many Americans have forgotten what normal looks like. Normal is certainly not a 190-lb, 5 ft 4 in woman, nor is it a 228 lb, 5 ft 11 inch man. But Americans have put on so much weight that the prevailing view of what constitutes "normal" weight has been revised upward. Normal is closer to what we see in old movies from the 1940s and '50s with people like Jimmy Stewart and Donna Reed. That's what we are supposed to look like.

So Don actually remains mildly overweight but is judged as "too skinny," or even cancer-ridden, by friends and family.

Ignore such comments. As you lose pounds and approach a truly desirable weight, realize that you are returning to the normal state, not the vision of "normal" now held by most Americans.

Getting vitamin D right

Vitamin D is, without a doubt, the most incredible "vitamin"/prohormone/neurosteroid I have ever encountered. Frankly, I don't know how we got anything accomplished in health pre-D.

Unfortunately, people I meet rarely take their vitamin D in a way that accomplishes full restoration of vitamin D blood levels. It really isn't that tough.

Here's a list of common tripping points with vitamin D:

"I take vitamin D: 1000 units a day."
This is probably the most common mistake I see: Taking a dose that is unlikely to yield a desirable blood level. (We use 60-70 ng/ml of 25-hydroxy vitamin D as our target.) Most men and women require 6000 units per day to achieve this level. There is substantial individual variation, however, with an occasional person needing much more, a rare person requiring as little as 1000 units.


"I bought some vitamin D on sale. They were white tablets."
Time and again, patients in my office who initially have had successful vitamin D replacement, despite being reminded that only oil-based forms should be taken, switch to tablets. While they initially showed a 25-hydroxy vitamin D blood level, for instance, of 67 ng/ml on 8000 units per day with an oil-based capsule, they switch to a tablet form and the next blood level is 25 ng/ml. In other words, tablets are very poorly or erratically absorbed.

I have had people use tablets successfully, however, by taking their vitamin D tablets with a teaspoon of oil, e.g., olive oil. Oil is necessary for full absorption.


"I'm going to Florida. I'll stop my vitamin D because I'm going to lay in the sun."
Wrong. 90% of adults over 40 years old have lost the majority of their ability to activate vitamin D in the skin. A typical response might be an increase in blood level from 25 to 35 ng/ml--a 10 ng increase with a dark brown tan.

There is an occasional person who, with sun exposure, increases blood levels substantially. This can occur in both fair-skinned and dark-skinned people, though I've never seen it happen in an African-American person. The occasional person who maintains the ability to convert vitamin D with sun exposure, or young people, should seasonally adjust their vitamin D dose, e.g., 6000 units winter, 3000 units summer, or some other regimen that maintains desirable blood levels. You can see that monitoring blood levels (we check levels every 6 months for the first 2 years) is crucial: You cannot know what your vitamin D needs are unless you assess 25-hydroxy vitamin D levels.


"I drink plenty of milk. I don't think I need to take vitamin D."
Oh, boy. This is so wrong on so many levels.

First of all, no adult should be drinking plenty of cow's milk. (A discussion for another day.) Second of all, cow's milk averages 70 units of vitamin D, often the D2 form (ergocalciferol), per 8 oz. Even if the FDA-mandated 100 units per day were present, an average adult dose of 6000 units would require 60 glasses of milk per day. Can you say "diarrhea"?

Likewise, other food sources of vitamin D, such as fish (300-400 units per serving) and egg yolks (20 units per yolk), are inadequate. This makes sense: Humans are not meant to obtain vitamin D from food, but from sun exposure over a large body surface area. And this is a phenomenon that is meant to occur only in the youthful, ensuring that nature takes its course and us older folks get old and make way for the young (i.e., unless we intervene by taking vitamin D supplements).


"My doctor said that my vitamin D blood level was fine. It was 32 ng/ml."

Let's face it: By necessity, your overworked primary care physician, who manages gout, hip arthritis, migraine headaches, stomach aches, prostate enlargement, H1N1, depression, etc., is an amateur at nearly everything, expert in nothing. Nobody can do it all and get it right. Likewise vitamin D. The uncertain primary care physician will simply follow the dictates of the laboratory form that specifies "30-100 ng/ml" as the "normal" or "reference range." Unfortunately, the laboratory often quotes population distributions of a lab measure, not an ideal or desirable level.

To illustrate the folly of population distributions of a measure, imagine you and I want to know what women weigh. We go to a local mall and weigh several thousand women. We tally up the results and find that women weigh 172 lbs +/- 25 lbs (the mean +/- 2 standard deviations). (That's true, by the way.) Is that desirable? Of course it isn't. Population average or population distribution does not necessarily mean ideal or desirable.


"My husband's doctor said he should take 4000 units per day. So I just take the same dose."
That would be fine if all adults required the same dose. However, individual needs can vary enormously. A dose that is grossly insufficient for one person may be excessive for another. Once again, vitamin D dose needs can be individualized by assessing 25-hydroxy vitamin levels in the blood.


"I don't need to take vitamin D. I already take fish oil."
I suspect this mistaken belief occurs either because people confuse fish oil with cod liver oil, which does contain some vitamin D. (Cod liver oil is not the best source of vitamin D, mostly because of the vitamin A content; also a discussion for another time), or because they've heard that eating fish provides vitamin D. However, fish oil capsules do not contain vitamin D unless it is added, in which case it should be prominently and explicitly stated on the label.


"I don't have to take vitamin D. It's summer."

For most people I know, if it's a bright, sunny July day, where are they likely to be? In an office, store, or home--NOT lying in the sun with a large body surface area exposed. Also, most people expose no more than 5-10% of surface area in public. I doubt you cut the grass in a bathing suit. Because of modern indoor lifestyles and fashion, the majority of adults need vitamin D supplementation year-round.


I advise everyone that gelcap vitamin D is preferable. Some, though not all, liquid drop forms have also worked. Take a dose that yields desirable blood levels. And blood levels of 25-hydroxy vitamin D are ideally checked every 6 months: in summer and in winter to provide feedback on how much sun activation of D you obtain.

If your doctor is unwilling or unable to perform vitamin D testing, fingerstick vitamin D test kits can be obtained from Track Your Plaque.

Jimmy Moore's thyroid adventure

My friend, Jimmy Moore of Living La Vida Low Carb, describes his thyroid experience here.

As Jimmy points out, he was looking for a way to jump-start a 50-lb weight loss. In my experience, low thyroid hormone levels ("hypothyroidism") are an exceptionally common cause for weight gain. Correcting even marginal hypothyroidism can facilitate weight loss, often resulting in 10 or more pounds of weight loss within the first month.

Unfortunately, Jimmy's thyroid hormone panel proved normal: TSH 1.3, thyroid hormones free T3 and free T4 in the mid- to upper-half of the reference range.

I say "unfortunately" because it is really an easy, inexpensive, and benign solution for losing weight. (I don't, of course, wish that Jimmy or anyone else develops a thyroid condition. But it really can provide gratifying weight loss results when thyroid function is low.) Jimmy might consider taking his oral temperature first thing in the morning as another means of assessing the adequacy of thyroid function.

Perhaps you will be luckier than Jimmy and have thyroid dysfunction that can be corrected and jump-start your weight loss program. Fingerstick thyroid test kits like the one Jimmy used are available here from Track Your Plaque.
Interview with Jimmy Moore of Livin' La Vida Low-Carb

Interview with Jimmy Moore of Livin' La Vida Low-Carb

Here's my podcast interview with Jimmy Moore, host of the Livin' La Vida Low-Carb Show. (If you want to fast forward to the interview, go to time marker 41:20 on the slidebar.)



In the podcast, I talk about how the Track Your Plaque program and its focus on lipoprotein testing, along with the need to reverse the incredible epidemic of diabetes and pre-diabetes, led to elimination of all wheat from the diet and the book, Wheat Belly.

Comments (11) -

  • Might-o'chondri-AL

    9/8/2011 1:03:32 AM |

    To Pedro  (posted here since Server blocked),
    Journal Biological Chemistry 2003,278:54-63  "A Type 1 Diabetes-related Protein from Wheat" that refers to globulin (a storage molecule of wheat) being antigenic for autoimmune problems was where I saw wheat genome estimated in 2002 to be 16.5 gigabase. I read that article when tried to track down Doc's reason to declare wheat implicated in Type 1 diabetes. Full article at www. jbc.org/content/278/1/54.full

    A 2010 reference to wheat genome is in journal Cytogenic and Genome Research, Vol. 129, No. 1-3, 2010 abstract's 1st sentence refers to wheat genome as 1C-17Gbp. English abstract at http://content.karger.com/
    produktedb/produkte.asp?doi=313072

    As I understand it 1 giga-base   =  109 base pairs, and mega-base =  106 base pairs; it's not a formula like that used to compare computer bytes of giga-bytes and mega-bytes.

    You might have research use for the Harvard Gene Index Project's Computational Biology & Functional Genomics Laboratory; if use link below look at top of page and see a category for "Gene Indices", click there to then choose from subjects "Plants", "Animal" or several other indices.
    http://compbio.dfci.harvard.edu/tgi

  • Might-o'chondri-AL

    9/8/2011 1:06:38 AM |

    To Pedro  (Server blocked elsewhere),
    Journal Biological Chemistry 2003,278:54-63  "A Type 1 Diabetes-related Protein from Wheat" that refers to globulin (a storage molecule of wheat) being antigenic for autoimmune problems was where I saw wheat genome estimated in 2002 to be 16.5 gigabase. I read that article when tried to track down Doc's reason to declare wheat implicated in Type 1 diabetes. Full article at www. jbc.org/content/278/1/54.full

  • otterotter

    9/8/2011 2:35:31 AM |

    Dr.Davis,

    Just listened to the podcast, that's fantastic !

    I have been diagnosed with TD2 last Sept, and since then being on the very low carb. Everything went well except my total cholesterol went out of control, and in January it was 400.

    What I don't understand is my Lp(a) is close to 0 ( less than 5.0 mg/dL as it was reported).

    Here is my latest direct measurements from SPECTRACELL LAB in Huston.

    VLDL Particels: 122 nmol/L (needs to be < 85)
    Total LDL Particles : 1271 nmol/L (needs to be < 900)
    Non-HDL Particles: 1394 nmol/L (needs to be < 1000)
    RLP(Remnant Lipoprotein) 205 nmol/L (needs to be < 150)
    Small Dense LDL III: 552 nmol/L (needs to be < 300, marked as very high risk right now)
    Small Dense LDL IV: 96 nmol/L (needs to be  7000)
    Large Buoyant HDL 2b: 2045 nmol/L (needs to be > 1500)

    Apo B-100: 127 mg/dL (needs to be < 80)
    Lp(a) : less than 5 mg/dL (needs to be < 30)
    C-Reactive Protein-hs : 0.2 mg/L (needs to be < 1)
    Insulin: less than 4.0 uIU/mL (needs to be < 35)
    Homocycteine: 12.3 umol/L (needs to be < 11)

    Total Cholesterol: 259 mg/dL
    LDL: 159 mg/dL
    HDL: 59 mg/dL
    Triglycerides: 118 mg/dL
    Non-HDL-Chol : 200 mg/dL


    I already removed the cheese and eggs from the diet, I suspect I am APOE 4.

    Any comments on my pattern ?

    thanks!

    otterotter

  • Might-o'chondri-AL

    9/8/2011 2:53:25 AM |

    To DCMarc  (server blocked where belongs),
    Benfotiamine, a synthetic thiamine used in diabetic neuropathy, increases enzyme trans-keto-lase inside a cell. The use in diabetics and neuro-degeneration may (?) require professional consideration in cancer cases. Trans-keto-lase spurs cells to go into aerobic glycolysis (aerobic here refers to cell performing glycolysis despite oxygen being around for performing normal mitochondrial oxidative phosphorylation) for processing cells glucose; this aerobic glycolysis is the  famous Warburg effect and experimentally administering trans-keto-lase augments cancer cell proliferation (likewise experimentally spiking up thiamin increases trans-keto-lase).

    Trans-keto-lase works for diabetics & in neuro-degeneration because  it pushes cell's glucose (via transcription once cAMP binds to it)  into the hexose mono-phosphate shunt ( of D-glucose-6p to D-glucono-lactone 6P to D-glycr-aldhehyde-3-phosphate) called the Pentose  Pathway (where hexose forms into pentose). This  process generates NADPH which boosts anti-oxidant glutathione ( & thioredoxin) production inside the cell. Also NADPH brings on the  activation of  the cell's endoplasmic reticulum's Unfolded Protein Response which helps the endoplasmic reticulum (ER) tolerate dangerous endoplasmic reticulum stress (ER stress is significant in diabetes and neuro-degeneration).

    ER stress, with protein folding complications, sees NADP+ accumulate and so augmenting trans-keto-lase pushes quicker output of NADPH to keep pace; this  triggers the Unfolded Protein Response to induce Cu,ZnSOD expression that then alleviates the ER stress (ie: helps ER tolerate demanding conditions).  This helps in that it  keeps the stressed ER  ( a state that coincides with more local super-oxide O--),  from seeding the dangerous (and largely un-neutralizable) hydroxyl radicals (hydroxyl radicals come about when super-oxide related hydrogen peroxide  provokes Fenton  & Haber/Weiss reactions reducing Cu++ or Fe+++ ). This is similarly how trans-keto-lase also benefits cancer cells ( rampant cancer cell growth demands protein folding that formally stresses the ER); the prevention against reactive oxygen species means cancer cells don't suffer apoptosis (cell death).

    Diabetics use of Befotiamine ( a dynamic fat soluble thiamine trans-keto-lase booster) will  help them similarly with their ER stress . In  their case the shift to using their regularly high glucose in the Pentose Pathway will mean quicker degradation of that glucose than if cells used mitochondrial oxidative phosphorylation. This also means the glycation (Doc warns against this from high glucose)  and thus tissue cells levels of advanced glycation end products (AGE) will be less; blunting the amount of AGE messing with monocytes and less endothelial dysfunction  amount to less inflammation, less diabetic oxidative stress and likewise less alteration of the vascular tissue such as atherosclerosis.

    Experimentally induced diabetes is often done by feeding a very high  fat diet. Much of the fat in a very high fat diet  acts to drive down the level of trans-keto-lase due to a transcription adaptationum within 8 weeks in rodents. For humans thiamine (B1) is often recommended to diabetics; cauliflower is a nice thiamine source to make into trans-keto-lase.

  • Might-o'chondri-AL

    9/8/2011 6:26:09 AM |

    To  B. Smith (Server won't post where belongs ),
    Glutamine, an amino acid, is used by cancer cells to keep apoptosis (cell death) from happening in several ways. One way is how glutamine keeps the cell nucleus from condensing and stops the capsase 3 & capsase 8 cascades from starting apoptosis. The other way is how there is an increase in the  anti-oxidant glutathione synthesis when glutamine elevates NADPH (see comment above for ER stress).

    Tumor Necrosis Factor alpha (TNF) works to destroy a cancer cell by running down that cell's mitochondrial glutathione level; this needs to be replenished with glutathione from that cell's cytosol. Once there is a 35% plunge in mitochondrial glutathione that  alters the mitochondrial membrane so that it stops bringing in glutathione to the mitochondria and starts leaking out cytochrome c into that cell's cytosol (which can jump start an apoptosis program). Cancer cells' rapid growth strains the normal oxidative stress limits of a cell, so cancer cells draw in lots of glutamine to boost the level of ready glutathione inside that cell; then the cytosol can continually shore up the mitochondrial glutathione levels to prevent one of the apoptosis scenarios from starting .

    A cancer cell at some point has to "transform" to progress and needs lots of DNA at that stage; glutamine is needed for synthesis of cellular RNA & DNA. The bio-synthesis of nucleotides utilizes glutamine; and having lots of de-oxy-ribo-nucleotides around favors DNA replication at that cancer's key "transformation" stage (ie: S-phase). The use of glutamine by a cancer cell for converting into energy to run on, like some normal cells do, is not why cancer cells take up so much glutamine.

  • Galina L.

    9/8/2011 4:25:13 PM |

    @ Might-o'chondri-AL
    Dear Might, do you mind to tell what do you think about that cancer research result?
    l http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3117136/?tool=pubmed

  • Peter Silverman

    9/8/2011 6:58:08 PM |

    My cardiologist said, "look, I don't know about nutrition.  If you want to talk about nutrion, go talk to a nutritionist"

  • Might-o'chondri-AL

    9/9/2011 12:32:19 AM |

    Hi GalinaL,
    Cancer undergoes several oncongenic processes wherein the so-called epithelilial pheno-type cell (epithelial cells are +/-85% of cancer substrate cells) gets it's cell nucleus histones acetylated, which creates what is called "stemness"  (the ability of that cell to renew itself with potency, like our stem cells). This leads to a phase called epithelial-mesenchymal transition (where the morphing cell can go either way, either back to benign epithelial pheno-type or onward to dangerous mesenchymal pheno-type). It is when the enzyme histone acetyl-transferase no longer keeps that epithelial histone acetylated ( a sort of  limbo) that the epithelial cell's genetic expression gets knocked down permitting the further shift into full mesenchymal pheno-type .

    What is important to realize about cancer cell's taking over a cell's nuclear DNA is that when the pheno-type goes from epithelial to mesenchymal the cancer cell's mesenchymal pheno-type somehow still retains the ability to perform the stem cell "stemness" of indefinite replication. Your cited authors point out that keotones boost tumor growth (+/-2.5 times) and lactate boosts tumor metastasis (+/- 10 times); and  also that their metabolic use raises a cell's Acetyl-CoA and this increases the acetylation of histones causing more gene expressio. And so authors report limiting ketones and lactate in cancer seem to be the "achilles heel" to cut off in order to stop cancer's "stemness" (ie: inherent potential); their extrapolation from this is interesting as a theory..

    There are other processes beyond histone modification which show oncongenesis is not lineal. When the cancer cell is still just an epithelial pheno-type cell unit micro RNA (miRNA) of the miRNA-200 family group is un-methylated; and thus holds the epithelial pheno-type steady, because un-methylated miRNA isn't reactive enough for messenger RNA (mRNA) transcription. A 2nd stage is seen once hyper-methylation  occurs, while at the same time less miRNA is put out; this morphs the cancer cell into the mesenchymal pheno-type and at that stage metastasis is possible. While an advanced 3rd stage comes about when miRNA resurges somewhat; this is what makes extensive metastasis of cancer cells that have migrated start happening. (Lineal thinking about cancer is a trap, since it is methylation that lets cancer cells get going but later de-methylation that let's them thrive and patient outcome worsen).

    Warburg effect is suggested, by cited study, to be almost a lineal concept; which they propose to re-define as desireable if it simply limits lactate and ketone production in a cell. This theory has it's own trap because in the Warburg effect +/-60% of the carbon from glucose undergoing aerobic glycolysis in cancer cells is actually being used by cancer cells as a carbon scaffolding for "de novo" fatty acid synthesis to feed into fatty acid oxidation. In other words the elevated amount of cancer cell's aerobic glycolysis (Warburg effect) is really fostering fatty acid oxidation; and fatty acid oxidation increases cancer resistance.

    The cancer cells uncouple the mitochondria oxidative phosphorylation of glucose so that the a lot of the processing of glucose doesn't go all the way to normal completion of ATP production; instead cancer cells use the initial steps that perform oxidation of glucose to cleave off the carbon atoms from that glucose to use. In other words it is the mitochondrial uncoupling protein up-regulated by that cancer cell's genetic  transcription which, down the line, forces that cell to continue to escalate Warburg's aerobic glycolysis in order to keep up with energy demands as carbon skeletons get used up.

    Metaformin's use in cancer treatment was suggested by study's authors to support their "reverse Warburg" theory : that it is by forcing Warburg's aerobic glycolysis to occur, due to Metaformin,  which accounts for cancer control seen. This seems too lineal an interpretation of the events; especially with regard to preceding paragraph's explanation of how Warburg relates to unpredictable carbon molecule usage. Metaformin reliably does inhibit the mitochondrial complex 1; and this will stymie glucose (and also glutamate, which cancer cells prodigiously take in ) from going on to produce ATP. I would suggest that this also stops the oxidizing of glucose molecules and thus sparse carbon skeletons are available to make into fatty acids for burning.

    In addition Metaformin inhibiting mitochondrial complex 1 will also reduce fatty acid oxidation; this is because  NADH oxidation at that complex needs to happen in fatty acid oxidation. NAD+ is a crucial rate limiter in  fatty acid oxidation , but unless NADH can subsequently be re-oxidized as a molecule in the mitochondrial complex 1 it can't keep on driving fatty acid oxidation by lending out NAD+.  Metaformin use in cancer is even more complicated, because if the cancer has p53 then when glucose supply is low it manages to actually use more fatty acids to run on and then use auto-phagy house cleaning to avoid apoptosis death. Whereas, if a cancer does not have much p53 then Metaformin seems to be more effective in treating cancer.

  • Dr. William Davis

    9/9/2011 2:25:55 AM |

    Yup, and the nutritionist hawks the usual "cut your fat, eat more whole grains" line.

    It's a comedy of misinformation with advice from agencies paid for by your tax dollars.

  • Dr. William Davis

    9/9/2011 2:29:21 AM |

    Hi, otter--

    Obviously, I can provide only limited advice in a blog post.

    But I agree: Apo E4 is a prime consideration. However, keep in mind that small LDL remains the most atherogenic (plaque-causing) of all your patterns and still deserves the primary focus. Also, if this blood sample was drawn with ongoing weight loss, this alone can provide substantial distortions.

  • Galina L.

    9/9/2011 2:48:25 AM |

    Wow! I don't know who else would dissect that article like you did! I really, really appreciate you decision to replay on my question. Looks like  Metaformin could be healthful in more than one way in treating cancer.

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