Homocysteine and coronary plaque

If you’ve watched the news over the past year, you know that doubt has been cast over the idea that reducing homocysteine blood levels with high doses of B vitamins (B6, B12, and folic acid, or B9) results in reduced risk for heart attack.

Is the homocysteine concept dead? Shall we empty our bottles of costly B vitamins into the trash and move on?

I don’t think so. As detailed in one of our Track Your Plaque Special Reports from a few months ago, I think the homocysteine issue still deserves lots of respect and further investigation. After all, hundreds of clinical studies have connected higher homocysteine levels with greater risk for heart disease, stroke, and aneurysm. Numerous studies, for example, have repeatedly and consistently demonstrated a tripling of heart attack risk when homocysteine levels exceed 14 ?mol/l. Can we dismiss this association because several more recent studies—NORVIT, HOPE, and VISP—suggested that, when starting homocysteine levels are 12.5, that B vitamin supplementation does not reduce heart attack risk?

I think there’s lots more to know about the homocysteine connection. That said, I have never seen a patient who I thought had heart disease strictly because homocysteine was increased.

I believe that we can at least use homocysteine as an index of lifestyle: the higher the homocysteine, the poorer the diet, or the less effective the absorption of B vitamins (especially vitamins B12 and folic acid). Homocysteine levels of <9 micromol/l suggest both adequate intake and absorption of these B vitamins.

If homocysteine is tightly connected with risk for heart disease, yet supplementation of B vitamins fails to reduce risk, might there be another means of connection? Or, could both homocysteine and heart disease be connected in some way that has nothing to do with B vitamins?

Don’t close the book on homocysteine. Just because conventional experience fails to draw connection does not necessarily mean that none exists. If it’s any consolation, taking B vitamins has been correlated with better memory, concentration, and other health benefits, even if no reduction in heart disease develops.

Big heart scan scores drop

High heart scan scores of, say, greater than 1000 are more difficult to reduce than lower scores.

I learned this lesson early in the experience of trying to drop scores. In the first few years of trying to drop scores, I saw relatively modest scores of 20, 50, or 100 drop readily, even when the usual targets were not fully achieved, and even before the incorporation of some of the more exciting recent additions to the Track Your Plaque program, like vitamin D.

But big scores of 1000, 2000, or 3000 are a tougher nut to crack. In the first few years, what I usually saw was a slowing , or "deceleration," of growth from the expected rate of annual score increase of 30% that would continue for a year or two, followed by zero change. In the first year of effort, for example, a score increase of 18% was common. 10% was common in year two, then finally zero change in year three. Somehow, the more plaque you begin with, the more "momentum" in growth is present and the longer it takes to stop it. Kind of like stopping a compact car versus stopping a freight train.

But more recently, I'm seeing faster drops. Today, Charlie came to the office to discuss his second heart scan. 18 months earlier, Charlie's first scan showed a score of 3,112, high by anybody's standard.

His repeat score: 3,048. While the drop is relatively small on a percentage basis and may even fall within the expected rate of error for heart scans (which tends to be <2% at this high a score), I told Charlie that it still represented a huge success. Not only did he not increase his score by the expected 30% per year, he also brought a charging locomotive to a rapid stop.

Next year, Charlie is targeting a big drop. Given the tools he now has available, I'm optimistic that he will succeed.

Watch for the Track Your Plaque May, 2007 Newsletter in which we will detail Charlie's story further.

Does the American Heart Association diet reduce heart disease?

If you have a heart attack and land in the hospital where, invariably, you will have a heart procedure. Or, if you get a stent or coronary bypass operation, sometime before your discharge from the hospital, a well-meaning hospital staff dietitian will provide instruction in the American Heart Association (AHA) diet.

Does this diet reduce the risk of heart disease?

The answer depends on where you start. If you begin with a conventional American diet that is enormously influenced by convenience, food manufacturers like Nabisco, General Mills, Quaker Oats, ADM, and Cargill, or food distributors like McDonald’s, Pizza Hut, and Taco Bell, then the American Heart Association diet is indeed an improvement. But just a small one. If LDL cholesterol is the yardstick, the average reduction in LDL is between 10 and 15 mg/dl. This is the same amount of change you’d experience by adding 1 tablespoon of oat bran to your diet. Hardly worth boasting about. HDL, triglycerides, blood glucose, and body weight do not change.

The diet could be substantially better. After all, it’s become common knowledge that other diets, such as the so-called Mediterranean diet, the South Beach Diet, and similar broad projects result in far greater changes than the AHA diet dispensed by your hospital and cardiologist. These diets more effectively reduce LDL, raise HDL, reduce triglycerides, reduce C-reactive protein, reduce blood pressure. Diets like South Beach also yield substantial weight loss and reversal of diabetic tendencies, with the magnitude of benefit dependent on the amount of weight lost.

Why this stubborn adherence to the outdated concepts articulated in the AHA diet? Cardiologists would argue that insufficient data has been generated to permit widespread application of these diets. They also differ on whether they really work. Of course, the majority remain ignorant and dismiss them as fad diets.

A little digging into the financial disclosures of the AHA suggests another, more malignant influence: who is paying the bills? Until recently, drug manufacturers were major contributors to the AHA. However, more recently AHA administrators have become sensitive to the public perception that they might be nothing more than a voice box for the drug industry. They have since limited contributions from the drug companies to 8% of annual charitable revenues.

The drug manufacturers have been replaced by the food industry. In addition to food manufacturers that make the cereals on your grocery shelf, it includes the multi-national conglomerates that produce unimaginable revenues and carry enormous political clout, like ADM and Cargill. Ever wonder how it is that Honey Nut Cheerios received a “Heart Healthy” endorsement from the AHA?

The AHA diet does not provide the answers we’re looking for, not even close. It is a perversion from an organization that has its strings pulled by industry. The answers to health will not come from the AHA, AMA, the American College of Cardiology, the American Hospital Association, and it won’t come from your doctor. It won’t come from a titillating report on the evening news or Good Morning America. It will come from collective and expanding wisdom placed directly into the hands of the public. It will be untainted by the temptation of drug industry dollars. It will not be dirtied by million dollar contributions, or the multi-million dollar behind-closed-doors lobbying of the food manufacturers. It will come from the truth relayed to the healthcare-consuming public. I hope you recognize it when you see it.

If you want a healthy diet for your heart, throw away the pamphlets from the AHA unless you are partial to bread, breakfast cereals, corn, and the supporters of their misguided nutritional advice.

Vitamin K2 and coronary plaque

The vitamin K2 story, though still preliminary, is becoming increasingly interesting from the perspective of CT heart score reduction.

The origin of this concept came from some unexpected observations. One, the observation that osteoporosis (lack of bone calcium that leads to fractures) arises from deficiency of vitamin K2. Two, deficiency of K2 leads to unrestrained calcium deposition in animal models, leading to heart attack in just weeks.

Vitamin K2 has been largely ignored for years, since the more widely understood K1 is rarely deficient. K1 deficiency can occur from prolonged antibiotic use, or from severe malnutrition. But deficiency in otherwise well people is very uncommon. Vitamin K2, however, may be a different story. Deficiency may be common.

The Rotterdam Heart Study of cheese-eating Dutch showed that greater K2 intakes resulted in a halving of heart attacks. Cheese (traditional varieties, not Velveeta or other make-believe cheese products) is a modest source of K2, as is the Japanese native food, natto. (If you've ever seen natto, I dare you to eat it. I have a pretty strong stomach and curiousity for food, but natto is the one thing I could not eat--it is truly horrible.)

The weight of evidence suggests that vitamin K2 supplementation may prove to be a useful addition to your coronary plaque control program. Clearly, more data are needed, particulary therapeutic obserations, i.e., observing people who take dose X of a K2 prepartion and tracking some feedback measure, e.g., bone density, CT heart scan score, "events" like heart attack, etc.

Nonetheless, the K2 story is clearly worth reading about, perhaps even considering supplementation. Please watch for the Special Report on the www.cureality.com website in the coming days.

Exercise and blood pressure

The media has gotten a hold of a case report from the University of Maryland describing a 51-year old physician who, despite being a long distance runner, had a high heart scan score.

An example of the report can be found at

Heart Disease In A Marathon Runner: Is Too Much Exercise A Bad Thing?

http://www.sciencedaily.com/releases/2007/03/070315091100.htm in Science Daily.



"The mystery was all the more intriguing because his resting blood pressure and fasting cholesterol levels, the usual measures of cardiovascular health, were in the normal range."


When this man was put on a treadmill for a stress test, his blood pressure skyrocketed from a normal 118/78 to 230/78--extremely high, even for exercise. The physicians reporting the case raised the question of whether long-distance running represents a risk for heart disease and if the high blood pressure with exercise is a contributor or cause of the high heart scan score.

These are phenomena we are very familiar with. We have stressed the importance of exercise blood pressure as a trigger for coronary plaque for years. While 230/78 is clearly too high, we find that any blood pressure over 170/80 with exercise adds to the fire and can trigger plaque growth.

However, I think it is absurd to suggest that marathon running itself is a trigger of coronary plaque. I think it is far more likely that the person described in the report had lipoprotein(a), a potent trigger for both exercise-induced hypertension and high CT heart scan scores in seemingly well people. He likely also suffered from a deficiency of vitamin D deficiency, another contributor. There's no need to indict exercise.

If you are in the Track Your Plaque program, you know that stress tests are of questionable helpfulness for the detection of hidden heart disease. But they are useful for assessment of blood pressure responses during exercise. If BP exceeds 170/80 at 10 mets (a measure of exercise effort achieved by walking 3.4 mph at a 14% grade for 3 minutes), then blood pressure may be a contributor to your heart scan score.

"Fish oil is stupid"

"Fish oil is a waste of time and money. It's stupid. Just stop it."

So a patient of mine was advised by another physician when he complained that he occasionally experienced a fishy aftertaste.

This attitude perplexes me. After all the confirmatory data that support the enormous health benefits of omega-3 fatty acid supplementation, including the 11,000 participant GISSI-Prevenzione Trial, you'd think this attitude would be history. What's a little fish aftertaste when heart attack risk is slashed 28%?

Perhaps the tendency to pooh-pooh fish oil is because it's available as a nutritional supplement. This shouldn't make fish oil appear inconsequential. Far from it.

If you witness the extraordinary power for fish oil to reduce triglycerides, you will be immediately convinced of its effectiveness. The ability of omega-3 fatty acids from fish to eliminate intermediate-density lipoprotein (IDL), the persistent abnormal lipoprotein which signals an inability to clear dietary fats from the blood, can also convince you. More than 90% of people with excessive IDL have it completely eliminated by 4000-6000 mg of fish oil (providing 1200-1800 mg EPA + DHA) per day.

The fact that fish oil is available as a prescription "medication," as well as an over-the-counter supplement, causes some physicians to dismiss the power of the supplemental form. This is nonsense. The over-the-counter form is every bit as effective as the prescription form.

The makers of prescription Omacor also make the claim that their preparation is safer and purer. That may be true, but I'd like to see independent verification from the FDA, USDA, or an unbiased organization like Consumer Reports before I accept their marketing as fact--particularly at $120 to $240 per month! If Omacor proves to contain substantially less mercury and pesticide residues, then that will need to be factored in. (Please note that both Consumer Reports and Consumer Labs measured no substantial mercury or pesticide residues in their analyses of 16 and 41 brands, respectively.)

I try to persuade my colleagues that the idea of taking supplements is a wonderful trend that allows people to express ownership of their own health. What people need is guidance, not salesmanship for a more expensive version, nor dismissal of nutritional preparations that actually possess considerable benefits.

More Vitamin D and HDL

I’m seeing more and more of it and I am convinced that there is a relationship: significant boosts in HDL cholesterol from vitamin D supplementation.

To my knowledge this remains an undescribed and uncharacterized phenomenon. There have been several observers over the last two decades who have noticed that total cholesterol shows a seasonal fluctuation: cholesterol goes up in fall and winter, down in spring and summer; year in, year out. This phenomenon was unexplained but makes perfect sense if you factor in vitamin D fluctuations from sun exposure.

I have come across no other substantiating evidence about fluctuations of HDL. But I am convinced that I am seeing it. Replace vitamin D to a blood level of 50 ng/ml, and HDL goes up if it is low to begin with. If HDL is high to begin with, say, 63 mg/dl, it doesn’t seem to change.

But, say, starting HDL is 36 mg/dl. You take niacin, 1000 mg; reduce high-glycemic index foods like breakfast cereals, breads, cookies, bagels, and other processed carbohydrate foods; exercise four days a week; add a glass of red wine a day; even add 2 oz of dark chocolate. You shed 15 lbs towards your ideal weight. After 6 months, HDL: 46 mg/dl. Better but hardly great.

Add vitamin D at a dose of, say, 4000-6000 units per day (oil-based gelcap, of course!), and re-check HDL two or three months later: 65 mg/dl.

I’ve seen it happen over and over. It doens't occur in everybody but occurs with such frequency that it’s hard to ignore or attribute to something else. What I’m not clear about is whether this effect only occurs in the presence of the other strategies we use to raise HDL, a “facilitating” effect, or whether this is an independent benefit of HDL that would occur regardless of whatever else you do. Time will help clarify.

We are tracking our experience to see if it holds up, how, and to what degree on a more formal basis. Until then, a rising HDL is yet another reason—-among many!-—to be absolutely certain your 25-OH-vitamin D3 level is at 50 ng/ml or greater.

How high is an ideal vitamin D blood level? If 50 ng is good, is 60 or 70 ng even better? Probably not, but there are no data. We have to wait and see. Unlike a drug that enjoys plentiful “dose-response” data, there are no such observations for vitamin D into this higher, though still “physiologic,” range.

Thin ice

How long can an industry built on ignorance and deception continue its practices in the new Information Age?

I don’t think it can for long. I talk to hospital administrators who believe that their source of competition is the hospital across town, battling for the same patients. I speak to my colleagues, the cardiologists, who believe that the current model is sustainable—take every willing body to the catheterization laboratory or operating room for heart procedures, the revenue-generating engine of income and expanding heart programs.

I speak to primary care physicians, who are dumbfounded and perplexed and have no idea which way things are going. They are trapped in a peculiar position: most have signed contracts and are employees of the hospital. They are legally bound to support the cardiologists who take anybody possible to the catheterization laboratory or direct patients to other profit-making procedures.

Much of this system depends on the willingness of the participant, meaning you and the health care seeking public. What happens when the truth comes out and disseminates widely through the thinking populace? What happens to hospitals and physicians and the vast structures they’ve built when the bottom drops out for 50% of their “market?

The proverbial cow manure will hit the fan. Upheavals in the medical industry will rival the changes that the automobile or telephone brought early in the last century. Cardiologists, immense hospital heart programs, and the vast economic infrastructure they spawned will go the way of stage coach manufacturers and the telegraph.

What form will the broad exposure of detailed information in health take? I’m not sure, but it will certainly come. The collaborative efforts that created the Linux operating system and have challenged the monopoly of Microsoft Windows, or the emergence of the extraordinary Wikipedia as a repository of human knowledge that dwarfs the venerated Encylopedia Brittanica, will eventually overtake the American medical system, the heart disease industry in particular.

If you base your future on the welfare of your local hospital or the manufacturers of stents, operating room equipment for heart bypass, or similar industries, watch out. The ice is thin. And as the spring warms the air around you, it gets thinner.

The Track Your Plaque program is our first step in broadcasting the message of self-empowerment in heart health care and an attempt to wrestle control away from the profit-seeking forces that dominate. As we grow, we not only hope to broadcast the message more widely, but expand the message to other areas of health. I predict that the collaborative, let’s-all-pitch-in-and-help spirit of the Information Age, “version 2.0,” will spark the change.

Vitamin D and cancer

Although this is a Blog about heart scans and heart disease, I came across a helpful video from Dr. Joseph Mercola about vitamin D and cancer that's worth viewing. Though I do not agree with many of Dr. Mercola's on-the-edge views, he does come up with some good thoughts and, in this instance, a useful educational tool about vitamin D.

You can view his video (which he claims crashed his server, due to the excessive demand for downloads) by cutting and pasting the address into your URL bar (above):

http://v.mercola.com/blogs/public_blog/How-to-Reduce-Your-Risk-of-Cancer-By-50--8790.aspx

Also, for my many patients who I've directed to look in my Blog for Dr. Reinhold Vieth's webcast presentation on vitamin D, here's the address:

http://tinyurl.com/f93vl

Perhaps I carry on too much about vitamin D. But I've come to respect this "nutrient" as among the most powerful strategies I've seen for dramatically improving control over coronary plaque growth as well as other aspects of health, as Drs. Mercola and Vieth eloquently detail.

Lipoprotein(a), menopause, and andropause

Lipoprotein(a) is a curious lipoprotein. Not only is it a genetic pattern with numerous variations, it is also one that shows a predictable age-dependent rise.

Women in particular are prone to this effect, men to a lesser degree. As we age, many hormones recede, particularly growth hormone, testosterone, the estrogens (estradiol, estriol, estrone), progesterone, and DHEA, among others. This is not a disease but the process of senescence, or aging.

When we're young, estrogens, testosterone, and DHEA all exert suppressive effects to keep lipoprotein(a), Lp(a), at bay. But as a woman proceeds through her pre-menopausal and menopausal years, and as a male passes through his fourth decade, there is an accelerated decline of these hormones. As a result, Lp(a) crawls out of its cave and starts to sniff around.

Typically, a woman might have a Lp(a) of 75 nmol/l (approximately 30 mg/dl) at age 38. Ten years later, at age 48, her Lp(a) might be 125 nmol/l (app. 50 mg/dl), all due to the decline of estrogens and DHEA. A parallel situation develops in males due to the drop in testosterone. For this reason, it may be necessary to re-check Lp(a) once after the fourth decade of life if you've had a level checked in your younger years.

This opens up some interesting therapeutic possibilities. If receding hormones are responsible for unleashing Lp(a), hormones can be replenished to reduce it. In males, this is relatively straightforward: supplement human testosterone and Lp(a) drops about 25%.

In women, however, it's a bit murkier, thanks to the negative experince reported using horse estrogens (AKA Premarin) in the HERS Trial and Women's Health Initiative. You'll recall that women who take horse estrogens and progestins (synthetic progesterone) do not experience less heart attack and develop a slightly increased risk of endometrial and breast cancer. There was, however, a poorly-publicized sub-study that showed that women with Lp(a) experience up to 50% fewer heart attacks on the horse/synthetic combination.

Wouldn't it be nice to have a large trial examining the safety/advisability of human estrogens and progesterone? To my knowledge, no such confident study in a significant number of women exists, since there's so little money to be made with human hormonal preparations.

For these reasons, we use lots of DHEA, generally at doses of 25 to 50 mg per day. It makes most people feel good, boosts energy modestly, increases muscle, and reduces Lp(a) up to 18% in women, a lesser quantity in men.
Mocha Walnut Brownies

Mocha Walnut Brownies

Richer than a cookie, heavier than a muffin, brownies are ordinarily an indulgence that leaves you ashamed of your lack of restraint. Have one . .  . or two or three, and you will surely pack on a pound of belly fat.

But these mocha walnut brownies, as with other recipes I provide, will not pack on the pounds. With no wheat to trigger appetite, nor any readily-digestible carbohydrate to generate blood sugar highs and lows, you can have a nice brownie or two or three and nothing bad happens: You don’t send blood sugar sky-high, don’t trigger formation of small LDL particles and triglycerides, you don’t trigger appetite, you don’t gain a pound of belly fat. You simply have your brownie(s) and enjoy them.

Serve these brownies plain or topped with cream cheese, natural peanut or almond butter, or dipped in coffee.


Ingredients:
8 ounces unsweetened baking chocolate (100% chocolate)
4 tablespoons coconut oil or butter, melted
2 large eggs, separated
½ cup coconut milk (or sour cream)
2 teaspoons vanilla extract
2 cups ground almonds
2 tablespoons coconut flour
1 cup chopped walnuts
¼ cup unsweetened cocoa powder
2 teaspoons instant espresso
Sweetener equivalent to 1 cup sugar or to taste (e.g., liquid stevia, Truvía, erythritol)


Preheat oven to 350º F.

Melt chocolate using double boiler method or in 15-second increments in microwave. Stir in melted coconut oil or butter.

In small bowl, beat egg whites until frothy. Add egg whites, egg yolks, coconut milk, and vanilla extract to chocolate mixture and mix thoroughly by hand.

In separate bowl, combine ground almonds, coconut flour, walnuts, cocoa powder, espresso, and sweetener. Mix thoroughly.

Add dry mix to chocolate mix and mix together thoroughly. If dough is too stiff, add additional coconut milk, one tablespoon at a time.

Place mixture in 9-inch baking pan and bake for 25 -30 minutes or until toothpick withdraws dry.

Comments (11) -

  • Stephanie KL

    1/2/2012 5:54:10 PM |

    Does your pan need greasing prior to adding the batter?

  • Jennifer

    1/2/2012 8:16:40 PM |

    They look great, and I'll bet they are darned tasty, but you are also serving yourself a load of PUFAs with these and then you want to top them with more yet.  One brownie, maybe.  Two or three, no way I'd eat that much PUFA, even if it's coming from nuts and not corn or soy oils.    I don't mean to come across as a twit about this stuff, but if you are a "person in a certain metabolic state", like me,  then you have to really look close at these kinds of things.

  • Might-o'chondri-AL

    1/3/2012 11:45:22 PM |

    For Laura (continuation from previous Dec. 2011 thread "Are you hungry"),
    Assume very  low carb & paleo styled dieters are going with high dietary fat to complement reasonably high protein yet some feel weight loss is not enough. Dietary fat is more than a molecule glob we just act on and has signaling properties for our cells. We synthesize distinct fat molecules inside us from different dietary fats by splitting some apart & elongating into new forms.

    Palmitic acid ( palmitate) is what I suggest as involved in stalled weight loss for low carb & paleo dieters since admonishments to eat more fat don't isolate the types of fatty acids metabolic signal cascades. De-novo lipogenesis from carbs forms palmitic fatty acid but some may benefit from restricting other palmitate sources.  68% of the fat "burned" is usually palmitic acid.

    A mitochondria inside a cell has 2 mitochondrial membranes and to "burn"  most fat (like palmitate) inside that mitochondria  2  molecules are involved. A carnitine based enzyme (carnitine palmitoyl transferase, CPT) can only shunt  fatty acid like palmitate into place for "burning" when there is a free unbound CoA (co-enzyme A) to work with.

    A high fat diet frequently ties up +/- 90% of cellular mitochondrial CoA with fatty acid acyls (as acyl CoA). Coconut oil is only 7-10% palmitic acid and some of the coconut oil's other fatty acids do not need carnitine (CPT) to get into place for "burning" inside a mitochondria. In other words coconut oil fatty acids get "burned" promptly and it doesn't tie up much CoA, which leaves more " free" CoA for other fatty acids to use in order to get into place for "burning". This is part of how coconut oil boosts fatty acid oxidation.

    High protein intake (over time, not as a single meal response) influences the mitochondria;  but let me specify first how it affects skeletal muscle mitochondria. In the inner mitochondrial membrane there is uncoupling protein 3 (UCP3) that is upregulated from a high protein diet. The U.N.'s WHO sets minimum daily protein requirement at 0.85 gr protein/kg. body weight & thus 1.7  - 2.0 gr protein/kg. body weight is a practical description of  high protein  (note: chronic kidney disease and some medical conditions are decidedly not suitable for high protein intake).

    Skeletal muscle UCP3 doesn't work to lower a mitochondria's membrane potential and as such doesn't make that cell use more oxygen. UCP3 causes a type of "uncoupling" whereby it "spills" some protons from the mitochondria's electron transport chain of ATP energy production and results in fatty acid anions (ie: fatty acid hydrolyzed be mitochondria UCP3 splits off a proton). Then that fatty acid anion can fit being shuttled back out from inside that mitochondria to ease the mitochondrial fatty acid burden.

    The effect here, from high protein increasing UCP3 expression, is to "free" up a CoA for each fatty acid shunted out and this then gives that mitochondria more "free" CoA that can then be put to  work with a carnitine enzyme (CPT) to put some of the backed up fatty acid load into position for "burning" to make ATP energy. This is part of how high protein diets increase fatty acid oxidation in skeletal muscle.

    Now, back to palmitate as a dietary fat; consider these food choices where 150 gr. liquid non-fat Kefir = 18 mg. palmitic acid vs 150 gr. liquid regular milk = 1,500 mg & then also compare 150 gr. of cooked garbanzo ( basis of hummus) = 300 mg. palmitic acid vs 150 gr. beef jerky (an example for solid meat protein) = 1,800 mg. palmitic acid. Since when one is trying to lose weight often the desired fat tissue signalling lipo-kines are not doing what normally would .

    Dieters adipose tissue often begin with altered lipo-kine expression and demonstrate multiple gene expression peculiarities that persist even when they have already lost a good bit of weight. Palmitate is implicated, for example, when low circulating adiponectin levels are problematic.

    Aside from the negative effects of the palmitate derivative ceramide (not detailed here) there is the risk that high palmitate interacts with the local inflammatory cells' TLR4 (toll like receptor) engaging NFkB (nuclear factor) causing that cell's enzyme NADPH oxidase to generate excessive reactive oxygen super-oxide molecules. One unknown is whether an individual is vulnerable to any side effect(s) or if  local tissue responds "normally" to elevated levels of palmitate by using the super-oxide spun off as a signaling molecule for a proper metabolic response.

    One concern is that some people with elevated palmitate might get increased endoplasmic reticulum (ER) stress ( ER inside cell is where proteins must fold properly). Doc's readers know we vary in ApoE genetics; and some ApoE isoform % heritage is one reason high palmitate makes them more prone to induced ER stress in certain tissue cells.

    Hunter-gatherer & pastoral people respond to high fat diet with sleekness because high saturated fat over time (not a meal) causes the mitochondrial membrane (paradoxically) to actually become higher in % of polyunsaturated fatty acid (PUFA) content than a low saturated fat intake does. Anyway the result is a more flexible mitochondrial membrane for responding.

    Their proclivity toward high fat fuel "burning" (hunters prefer the fattest parts & herders get lots of milk fat) initially makes that mitochondria put out  lots of super-oxide which becomes a hydroxyl radical that snatches an atom of hydrogen from a PUFA  in that phospho-lipid mitochondrial membrane. Then that metabolite becomes a carbon cored fatty acyl free radical which the cellular oxygen makes into a per-oxyl, which becomes a substrate for spinning off molecules called alkenals (ex: 4-hydroxy-nonenal).

    In the liver (and some tissues) a different type of UCP in the mitochondrial membrane "normally" responds to the alkenal signal  & then UCP 2 "uncouples" to varying degrees of severity so that protons shunting through the electron transport chain (ETC) "spill" protons. In this case the result of upregulating UCP2 in the liver due to a high fat diet is to make the ETC lose efficiency (due to "spill" lessening proton force ) and  that mitochondria must use more oxygen working more to churn out the correct amount of ATP downstream. If one's genetics somehow stymie the increase in UCP2 in any one of the tissue groups with UCP2 function in that inner mitochondrial membrane then high fat intake itself doesn't necessarily trigger this beneficial adaptative response.

    The "normal" side effect from this in the liver cell is reduced mitochondrial  membrane potential from the UCP2, but increased "burning" of fat there; so the hunter (or pastoral) stays sleek because this set up tends to make one lose weight and also keep liver metabolic rate up as they age.  Meanwhile UCP2 alters the dynamic so that less ROS is generated at the mitochondrial staging complex 1; it is a type of self regulatory feedback arrangement where the signal is in reaction to high fat intake. I suspect epigenetic insults to UCP2 may also confound the efforts of some dieters.

    To complete the picture it is relevant  that a high protein diet also upregulates UCP2 acting in key mitochondria; although skeletal muscle UCP2 is not as strongly influenced by high protein diet and it has more response with UCP 3 (skeletal muscle has more of it to begin with) . Our ancestors were feast or famine prone and caloric restriction is another factor which increases both UCP 2 & UCP 3 levels. Thus agriculturists which didn't/don't over consume usually stay slim despite carb based diets & more carb driven de-novo lipo-genesis of palmitate ( with Doc's supplements my labs are good seemingly eating  120+ gr. carbs daily).

    If I were stalling on  low carb/paleo-ish diet I would consider adding in olive oil because the oleic acid counter-acts the action of  palmitate (ex: eat hummus made with olive oil).  Cutting back on palmitate intake conceivably could be off-set by experimenting with more coconut oil (not to be confused with palm oil)  and/or adding in more select nuts/seeds for fat. I would also break ranks with theory and try a protein spell without animal/fowl fat by substituting casein (ex. fat free kefir/yogurt quark) & fish (while keeping up fish oil) & moderate daily portion of hummus to keep protein high (assuming no health contra-indication).

    Excessive (moderation is an individual variable) intake of alpha linolenic acid (ALA) actually decreases the amount of circulating DHA long chain PUFA synthesized and makes less available to incorporate into the cellular membranes. The role of DHA in cell membranes is beneficial for metabolic signaling ; membranes are not just casings of a uniform bagging. So replacing dietary palimitic acid fat with almonds (no ALA, 9% saturated) or sesame tahini (no ALA, 13% saturated), as opposed to loading up on flax (57% ALA, 9% saturated) or walnut (7% ALA, 16% saturated ) or canola (10% ALA, 6% saturated)  for fat may help contribute to other fatty acid signal cascades that might bump one past a weight stall even if already taking maximum fish oil.

  • Dr. William Davis

    1/4/2012 1:40:30 AM |

    Depends on your pan, Stephanie.

    I usually do not and it comes out just fine. If you are uncertain, coconut oil works best.

  • lola

    1/5/2012 4:54:42 AM |

    WOW - I am going to have to read this multiple times to absorb.. ha - but thanks... interesting

  • Ronnie

    1/6/2012 12:31:26 AM |

    I know low carb is the way to go for all genotypes, including Apoe 3/4 people.  But I've read that LOW fat is also necessary to lower heart disease risk for these 3/4's, not moderate fat.  Do you agree?

  • the internet

    1/9/2012 5:01:47 PM |

    ronnie, you cant go low fat and low carb simultaneously

    a diet that was 80% protein would kill you

  • Judd

    1/16/2012 10:34:02 PM |

    Hi,

    Just made these brownies.  Seems like the recipe could use less flour in order for it to be not so firm and dry.  Or increase the amount of coconut milk in the recipe.  I had to use a whole can of coconut milk and some water and regular milk as well to make the consistency to where I could spoon it into a pan.  Tastes and smells great so far...Thx

    Judd
    AZ

  • Judd

    2/9/2012 3:08:24 PM |

    Can''t get these to come out right.  Too dry even with half the amount of flour.  As soon as I add the egg chocolate mixture to the dry, it just all drys up.  Any bakers or ideas out there??

    Thanks, Judd

  • Dr. William Davis

    2/12/2012 2:56:45 PM |

    Try adding more liquid, e.g., sour cream or coconut milk, until you get a moldable dough consistency.

  • Eric C

    2/14/2012 1:58:19 AM |

    Dr. Davis,
    I''d like to add to the PUFA (aka: nuts) restriction argument here. When I initially started low-carb, I ate a lot of nuts. But nuts have a few problems:

    1. Copper
    2. PUFA
    3. Phytosterols

    There are more problems. But increasing copper & PUFA levels in the body causes big problems in the long-term since these two react so readily. After a year or two of eating maybe 50-100g of various nuts per day, my congenital bicuspid aortic valve developed a murmur and mild heart enlargement due to my aortic valve becoming moderately-severely stenosed. The cardiologist I visited thought I would need surgery and/or "wouldn''t make it past 40" without surgery. But I changed my diet. After increasing my grass-fed butter (saturated fat), beef tallow, etc. (low omega-6) fats and restricting PUFA to a bare-minimum (in addition to a few other things, though), the murmur is actually going away. It''s almost gone. I''m only 30, though. I can''t believe it. I was in serious condition just by eating 50-100g of various nuts per day... (odd since most studies show "benefit" on HDL/LDL). But now I''m realizing that despite an improvement in ratio of HDL/LDL, nuts increase lp(a) and oxidized LDL in the long-run like no other.

    PUFA''s are dangerous in excess. I avoid them like the plague now.

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