DHA: the crucial omega-3 - Davis

DHA: the crucial omega-3  

Of the two omega-3 fatty acids that are best explored, EPA and DHA, it is likely DHA that exerts the most blood pressure- and heart rate-reducing effects. Here are the data of Mori et al in which 4000 mg of olive oil, purified EPA only, or purified DHA only were administered over 6 weeks:


□ indicates baseline SBP; ▪, postintervention SBP; ○, baseline DBP; •, postintervention DBP; ⋄, baseline HR; and ♦, postintervention HR.

In this group of 56 overweight men with normal starting blood pressures, only DHA reduced systolic BP by 5.8 mmHg, diastolic by 3.3 mmHg.

While each omega-3 fatty acid has important effects, it may be DHA that has an outsized benefit. So how can you get more DHA? Well, this observation from Schuchardt et al is important:

DHA in the triglyceride and phospholipid forms are 3-fold better absorbed, as compared to the ethyl ester form (compared by area-under-the-curve). In other words, fish oil that has been reconstituted to the naturally-occurring triglyceride form (i.e., the form found in fresh fish) provides 3-fold greater blood levels of DHA than the more common ethyl ester form found in most capsules. (The phospholipid form of DHA found in krill is also well-absorbed, but occurs in such small quantities that it is not a practical means of obtaining omega-3 fatty acids, putting aside the astaxanthin issue.)

So if the superior health effects of DHA are desired in a form that is absorbed, the ideal way to do this is either to eat fish or to supplement fish oil in the triglyceride, not ethyl ester, form. The most common and popular forms of fish oil sold are ethyl esters, including Sam’s Club Triple-Strength, Costco, Nature Made, Nature’s Bounty, as well as prescription Lovaza. (That’s right: prescription fish oil, from this and several other perspectives, is an inferior product.)

What sources of triglyceride fish oil with greater DHA content/absorption are available to us? My favorites are, in this order:

Ascenta NutraSea
CEO and founder, Marc St. Onge, is a friend. Having visited his production facility in Nova Scotia, I was impressed with the meticulous methods of preparation. At every step of the way, every effort was made to limit any potential oxidation, including packaging in a vacuum environment. The Ascenta line of triglyceride fish oils are also richer in DHA content. Their NutraSea High DHA liquid, for instance, contains 500 mg EPA and 1000 mg DHA per teaspoon, a 1:2 EPA:DHA ratio, rather than the more typical 3:2 EPA:DHA ratio of ethyl ester forms.

Pharmax (now Seroyal) also has a fine product with a 1.4:1 EPA:DHA ratio.

Nordic Naturals has a fine liquid triglyceride product, though it is 2:1 EPA:DHA.

By Dr. William Davis
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Read the complete article here.

Niacin significantly reduces oxidative stress

Am J Med Sci. 2013 Mar;345(3):195-9. doi: 10.1097/MAJ.0b013e3182548c28.

Niacin administration significantly reduces oxidative stress in patients with hypercholesterolemia and low levels of high-density lipoprotein cholesterol.

Hamoud S, Kaplan M, Meilin E, Hassan A, Torgovicky R, Cohen R, Hayek T.

Source

Internal Medicine E Department (SH, AH, TH) and Lipid Research Laboratory (SH, EM, TH), Technion Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences, Rambam Medical Center, Haifa, Israel; Clinical Biochemistry Laboratory (MK), Technion Faculty of Medicine, Rambam Medical Center, Haifa, Israel; and Medical Department (RT, RC), Merck, Sharp and Dohme, Hod Hasharon, Israel.

Abstract

ABSTRACT:: Oxidative stress has been implicated in the pathogenesis of cardiovascular disorders, including atherosclerosis. In pharmacological doses, niacin (vitamin B3) was proven to reduce total cholesterol, triglyceride, very-low-density lipoprotein, and low-density lipoprotein levels, and to increase high-density lipoprotein (HDL) levels. The aim of this study was to evaluate the effect of niacin treatment in patients with low levels of HDL cholesterol
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Read complete article here.

Look AHEAD halted: Lifestyle management fails to reduce hard CV outcomes in diabetics - O'Riordan

Look AHEAD halted: Lifestyle management fails to reduce hard CV outcomes in diabetics

October 19, 2012 Michael O'Riordan

 

Los Angeles, CA - The Action for Health Diabetes (Look AHEAD) study, a trial comparing an intensive lifestyle-intervention program aimed at achieving and maintaining weight loss and fitness in patients with type 2 diabetes, has been stopped for futility.

 

A large cardiovascular-outcomes study funded by the National Institutes of Health that included 5145 adults with diabetes and a body mass index >25 kg/m², Look AHEAD failed to show a difference in the rate of nonfatal MI, nonfatal stroke, death, or hospitalization for angina among patients randomized to an intensive lifestyle intervention and those randomized to a control arm consisting of education alone.

 

Despite significant reductions in weight and improvements in physical-fitness levels among patients with diabetes, investigators concluded that the intervention arm, which included individual sessions with a nutritionist and/or personal trainer, as well as group sessions and refresher courses, failed to provide any benefit in terms of cardiovascular outcomes.

 

Dr Anne Peters (University of Southern California, Los Angeles), one of the study investigators, said in an interview that the trial was successful on one level—namely, that patients lost weight and improved their fitness. Data published at four years showed that the intensive intervention led to weight loss of up to 10% in the first year and that patients maintained a 6.5% reduction in body weight in the following three years. Over an 11-year follow-up period, the patients reported a 5% reduction in body weight from baseline, said Peters.

 

In addition, early data showed that treadmill fitness levels, hemoglobin A_1c levels, systolic and diastolic blood pressure, HDL-cholesterol levels, and triglyceride levels were all significantly improved among patients in the lifestyle-intervention arm when compared with the control group. The only cardiovascular risk factor that remained unchanged with treatment was LDL-cholesterol levels.

 

Despite the lack of cardiovascular benefit observed in Look AHEAD, Peters stressed that diabetic patients should not stop exercising or begin eating anything they wish.

 

"We do know that weight loss and exercise can prevent diabetes," said Peters. "I am a big advocate of prevention, both early prevention of obesity altogether, as well as prevention of diabetes in individuals who have become overweight. Lifestyle changes can help prevent diabetes. Once you have diabetes, I think weight loss and exercise can have benefits, but they are not going to reduce the risk for the primary outcome that we set for Look AHEAD, which was a risk for macrovascular events or death."

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Read the full article here.

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Here is the official stated purpose of the Look AHEAD trial.

The primary objective of Look AHEAD is to examine, in overweight volunteers with type 2 diabetes, the long-term effects of an intensive lifestyle intervention program designed to achieve and maintain weight loss by decreased caloric intake and increased physical activity. This program will be compared to a control condition involving a program of diabetes support and education.

The primary hypothesis is that the incidence rate of the first post-randomization occurrence of a composite outcome, which includes

• cardiovascular death (including fatal myocardial infarction and stroke),
• non-fatal myocardial infarction,
• hospitalized angina, and
• non-fatal stroke,

over a planned follow-up period of up to 13.5 years will be reduced among participants assigned to the Lifestyle Intervention compared to those assigned to the control condition, Diabetes Support and Education.

 

Look AHEAD will also test for reductions in the incidence of three secondary composite outcomes and examine the effect of the intervention on cardiovascular disease risk factors, diabetes control and complications, general health, and quality of life, and psychological outcomes. The cost and cost-effectiveness of the Lifestyle Intervention relative to Diabetes Support and Education will be assessed.

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from https://www.lookaheadtrial.org/public/home.cfm

A comment by Dr. Jack Kruse had this to say about the trial...

Jack Kruse said...

You said, you could not find all cause mortality data for the stop. Not surprising to some of us. The trial was stopped because their hypothesis was being demolished. You and I both know it. But this post further supports my concerns with RCT and so called evidence based medicine. The modern health care complex trump this brand of medicine. I loathe it. There is nothing more dangerous to modern humans than evidence based medicine and we all remain unaware of those pitfalls. Peter has touched on just that here.

I wrote very recently in my Brain Gut 14 blog this: The manner in which we ask questions is deeply flawed in medicine. Here is where the major causative factor lies in medicine that too few are talking about in research literature. You need to know it. Positive findings, whether they are good or bad for our biology, are twice as likely to be published as negative findings.

This dramatically skews the meaning of what the evidence is really showing us in medicine. It is at the core why people do not get better with evidence based practices and remain a medical annuity for the system. This is a cancer at the core evidence-based medicine today. When you become aware of what you do not know, it becomes easier to get to optimal. They key is for you to avoid those pitfalls before you access the healthcare system. Unfortunately, physicians are paid on this data and that is why it appears to many people that doctors just don’t get it. Many of us do get it, but if we step out of line we get punished by the system. That is how I feel about this Look Ahead nonsense. I am more cynical than Peter. I think the trial was ended because a current growth industry in healthcare might have been placed in peril if the trial continued.

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from HyperLipid.

5 reasons not to worry about your cholesterol numbers

5 reasons not to worry about your cholesterol numbers

I do a lot of public speaking. As you might suspect, regardless of the specific topic I’m presenting the dietary recommendations I make are always essentially the same: high-fat, nutrient-dense and low in toxins. Since omega-6 vegetable oils are toxins, when I say high fat I’m talking about saturated and monounsaturated fat. You know this.

But a lot of people I speak to don’t. They fully steeped in 50 years of mainstream propaganda perpetuating the idea that saturated fats cause heart disease – primarily by raising blood cholesterol. So, inevitably, when I stand up in front of a group of people and tell them all to eat lots of saturated fat, I get a question that goes something like this:

But won’t that raise my cholesterol? And won’t high cholesterol give me a heart attack?

I haven’t yet perfected an answer that can dismantle a half century of cultural brainwashing about fat and cholesterol in less than 3 minutes. But I’m working on it.

In the meantime, I usually explain some variation of the following:

Point #1: Eating saturated fat doesn’t raise cholesterol levels in the blood

There’s no convincing evidence that eating saturated fat raises blood cholesterol. Stephan Guyenet spanked that old yarn to the curb in this recent blog post. In short, of all of the studies examining the relationship between saturated fat intake and serum cholesterol, only one found a clear relationship between the two and even that association was weak. The rest found no association at all.

Point #2: Eating cholesterol doesn’t (usually) raise cholesterol levels in the blood

Nor is there evidence that eating cholesterol in the diet raises cholesterol levels in your blood. A recent review of the scientific literature published in Current Opinion in Clinical Nutrition and Metabolic Care clearly indicates that egg consumption has no discernible impact on blood cholesterol levels in 70% of the population. In the other 30% of the population (termed “hyperresponders”), eggs do increase both circulating LDL and HDL cholesterol.

An increase of HDL is a good thing. And as it turns out, so is a boost of the type of LDL that eating saturated fat and cholesterol increases. We now know there are two different types of LDL: small, dense LDL, and large, buoyant LDL. Small, dense LDL is a significant risk factor for heart disease because it’s more likely to oxidize and cause inflammation. Large, buoyant LDL is not a risk factor for heart disease. And guess what? Eating eggs not only increases the benign large, buoyant LDL, but it also decreases the harmful small, dense LDL by 20%. I’ve written more about this here and here, and you can also watch some videos on this topic here.

Point #3: Even if eating saturated fat and cholesterol did raise cholesterol levels in your blood, it wouldn’t matter because “high cholesterol” isn’t a strong risk factor for heart disease.

This is the one that really spins people out. Even if they follow me on the first two points, their eyes tend to glaze over when I mention this one. As Mark Twain used to say:

The history of our race, and each individual’s experience, are sown thick with evidence that a truth is not hard to kill and that a lie told well is immortal.

Nowhere is that more true than with the lie that high cholesterol causes heart disease. It’s so deeply ingrained in our collective consciousness that it’s become an almost unassailable article of faith. That’s why people are so surprised to learn that there’s very little evidence to support the idea.

This point is the current bottleneck in my “3-minute” explanation, because it takes a while to explain why it’s not true. I’ve written about it extensively here, here and here. For the purposes of this brief article, we’ll have to leave it at this: both total and LDL cholesterol – which are the numbers your doctor, the media and everyone else seems to be concerned with – are only weakly associated with heart disease.

If “high cholesterol” were the cause of heart disease, you’d expect it to be a risk factor in:

1. All populations around the world.
2. In both men and women.
3. In people of all ages.

And you’d also expect that lowering cholesterol should prevent heart disease.
Makes sense, right?

Unfortunately for the lipophobes, the cholesterol hypothesis fails on all fronts.

1. High cholesterol is not a risk factor in all populations. The French have among the highest cholesterol levels in the world, and among the lowest rates of heart disease of any industrialized nation. The Austrians and other European nations are similar.
2. Women on average have 300% lower rates of heart disease than men, despite higher average cholesterol levels.
3. The rate of heart disease in 65 year-old men is 10 times that of 45-year old men. Yet high cholesterol is not a risk factor in men over 65. (In fact, men over 65 with low cholesterol (<150 mg/dL) are twice as likely to die from heart disease as those with normal or even "high" cholesterol.)

Finally, more than 40 trials have been performed to see if lowering cholesterol prevents heart disease. In some trials more people got heart disease, in others fewer. But when all the results were taken together, just as many people died in the treatment groups (those who took cholesterol-lowering drugs) as the control groups (those who did not).

Point #4: If you want to worry about your cholesterol numbers, forget about total cholesterol and LDL and pay attention to the ratio of triglycerides to HDL.

In general I’m not a fan of people worrying about their lipid panel numbers at all. Like Dr. Kurt Harris, I think this compulsive testing and re-testing of lipids that has become common in the Paleo community not only isn’t necessary, but may even be harmful. There’s still a lot we don’t know about how these numbers change on a day-to-day basis. What’s more, it’s not always easy to distinguish between cause and effect. Researchers made the mistake of assuming high cholesterol was the cause of heart disease, when in reality it’s much more likely that high cholesterol is a consequence of it.

But for crying out loud, if you’re going to get your lipds tested at least pay attention to the right numbers. And the most important number on a conventional lipid panel is the relationship between triglycerides and HDL. (Divide triglyercids by HDL to get it.) If that number is less than 2, this suggests you have mostly large, buoyant LDL – which is not a risk factor for heart disease. If that number is higher than 3, it suggests you have mostly small, dense LDL – which most certainly is a risk factor for heart disease.

Point #5: Eat good food and don’t worry about the numbers.

But in the end, even that ratio doesn’t matter so much. Why? Because the treatment is always the same! If your TG:HDL ratio is high (bad), what should you do? Eat a high-fat (saturated, of course) diet. This will reduce your triglycerides and small, dense LDL, and increase your HDL. Triple win. And if your TG:HDL ratio is low (good), what should you do? The exact same thing: eat a high-fat diet.

Conversely, replacing saturated fat with carbs, as we’ve been told to do for 50 years to protect ourselves from heart disease, actually contributes to it in three ways: it increases triglycerides and small, dense LDL, and decreases HDL.

Finally, I often get emails from people who’ve switched to a high-fat / Paleo-type diet expressing concern that their LDL and total cholesterol levels have gone up. My response usually has three parts: 1) don’t worry about it, because high total and LDL cholesterol do not cause heart disease; 2) the increase is usually temporary, and may be the result of the body curing itself of fatty liver (a good thing!); 3) don’t worry about it. Doesn’t hurt to remind them.

**Note: if your total cholesterol levels are very high (i.e. above 300 mg/dL), this may be an indicator of a metabolic abnormality or inflammatory process that needs to be addressed. Cholesterol is a repair substance in the body, and persistent elevations beyond a certain threshold may point to an underlying problem that hasn’t been identified.

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Read the complete article here.

Fish oil: The natural triglyceride form is better

Posted on February 2, 2011 by Dr. William Davis

If you have a choice, the triglyceride form of fish oil is preferable. The triglyceride form, i.e., 3 omega-3 fatty acids on a glycerol “backbone,” is the form found in the body of fish that protects them from cold temperatures (i.e., they remain liquid at low ambient temperatures).
Most fish oils on the market are the ethyl ester form. This means that the omega-3 fatty acids have been removed from the glycerol backbone; the fatty acids are then reacted with ethanol to form the ethyl ester.

If the form is not specified on your fish oil bottle, it is likely ethyl ester, since the triglyceride form is more costly to process and most manufacturers therefore boast about it. Also, prescription Lovaza–nearly 20 times more costly than the most expensive fish oil triglyceride liquid on a milligram for milligram basis–is the ethyl ester form. That’s not even factoring in reduced absorption of ethyl esters compared to triglyceride forms. Remember: FDA approval is not necessarily a stamp of superiority. It just means somebody had the money and ambition to pursue FDA approval. Period.
Taking any kind of fish oil, provided it is not overly oxidized (and thereby yields a smelly fish odor), is better than taking none at all. All fish oil will reduce triglycerides, accelerate clearance of postprandial (after-eating) lipoprotein byproducts of a meal (via activation of lipoprotein lipase), enhance endothelial responsiveness, reduce small LDL particles, and provide a physical stabilizing effect on atherosclerotic plaque.

But if you desire enhanced absorption and potentially lower dose to achieve equivalent RBC omega-3 levels, then triglyceride forms are better.

Here are cut-and-pasted abstracts of two of the studies comparing forms of fish oil.

Bioavailability of marine n-3 fatty acid formulations.

Dyerberg J, Madsen P, Moller JM et al.

Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Copenhagen, Denmark.

Abstract

The use of marine n-3 polyunsaturated fatty acids (n-3 PUFA) as supplements has prompted the development of concentrated formulations to overcome compliance problems. The present study compares three concentrated preparations – ethyl esters, free fatty acids and re-esterified triglycerides – with placebo oil in a double-blinded design, and with fish body oil and cod liver oil in single-blinded arms. Seventy-two volunteers were given approximately 3.3g of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) daily for 2 weeks. Increases in absolute amounts of EPA and DHA in fasting serum triglycerides, cholesterol esters and phospholipids were examined. Bioavailability of EPA+DHA from re-esterified triglycerides was superior (124%) compared with natural fish oil, whereas the bioavailability from ethyl esters was inferior (73%). Free fatty acid bioavailability (91%) did not differ significantly from natural triglycerides. The stereochemistry of fatty acid in acylglycerols did not influence the bioavailability of EPA and DHA.

(Full text of the Dyerberg et al study made available at the Nordic Naturals website here.)

Eur J Clin Nutr 2010 Nov 10.

Enhanced increase of omega-3 index in response to long-term n-3 fatty acid supplementation from triacylglycerides versus ethyl esters.

Neubronner J, Schuchardt JP, Kressel G et al.

Institute of Food Science and Human Nutrition, Leibniz Universität Hannover, Am Kleinen Felde 30, Hannover, Germany.

Abstract

There is a debate currently about whether different chemical forms of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are absorbed in an identical way. The objective of this study was to investigate the response of the omega-3 index, the percentage of EPA+DHA in red blood cell membranes, to supplementation with two different omega-3 fatty acid (n-3 FA) formulations in humans. The study was conducted as a double-blinded placebo-controlled trial. A total of 150 volunteers was randomly assigned to one of the three groups: (1) fish oil concentrate with EPA+DHA (1.01?g+0.67?g) given as reesterified triacylglycerides (rTAG group); (2) corn oil (placebo group) or (3) fish oil concentrate with EPA+DHA (1.01?g+0.67?g) given as ethyl ester (EE group). Volunteers consumed four gelatine-coated soft capsules daily over a period of six months. The omega-3 index was determined at baseline (t(0)) after three months (t(3)) and at the end of the intervention period (t(6)). The omega-3 index increased significantly in both groups treated with n-3 FAs from baseline to t(3) and t(6) (P < 0.001). The omega-3 index increased to a greater extent in the rTAG group than in the EE group (t(3): 186 versus 161% (P < 0.001); t(6): 197 versus 171% (P < 0.01)). Conclusion: A six-month supplementation of identical doses of EPA+DHA led to a faster and higher increase in the omega-3 index when consumed as triacylglycerides than when consumed as ethyl esters.

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Read the full article here.

Should We Be Concerned About Cholesterols?

Robert K. Su, MD  interviewed with Dr. Uffe Ravnvskov, on the Carbohydrates Can Kill Podcast show. Dr. Ravnvskov is an internist/nephrologists who has done lots of research in the roles of cholesterol in our health. He shared with us the reasons why treating cholesterol is unnecessary and harmful.

Read the full article here

Epic Saturated Fat Experiment

Read the full article here.
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Thursday, August 11, 2011

Epic Saturated Fat Experiment

The Effects of 15 days of 100 Grams of Saturated Fat Per Day on Cholesterol Levels in a healthy adult male.

By: Bryan Stell: BS West Chester University PA Exercise Science/Nutrition

Objective: It is widely believed that saturated fat in the diet increases blood cholesterol levels, promotes poor health as well as the progression of heart disease and atherosclerosis. The goal of this experiment is to compare pre and post bloodwork following 15 days of ~100g/saturated fat consumption per day to determine if there is any merit in this widely held belief.

Introduction: Saturated fat and cholesterol have long been avoided in the diet due to their believed link to heart disease and atherosclerosis. When saturated fat crosses the lips, some ignorant fool may shout " OMG, Yer gonna have a heart attack!" Or, "that bacon is clogging your arteries." For some 50 years food marketers and pharmaceutical companies have perpetuated these ideas, even though science is demonstrating that total cholesterol is an awful predictor of coronary heart disease (CHD) and that total LDL cholesterol or "bad" cholesterol is not much better. Furthermore, the entire case against saturated fat is inextricably linked to the idea that high cholesterol causes heart disease and that saturated fat in the diet increases blood cholesterol levels.

The USDA's 2010 dietary guidelines continue with the vilification of saturated fats by recommending they make up no more than 7% of one's daily caloric intake. This is down from a previously recommended upper limit of 10%. Instead they recommend replacing saturated fats with more mono-unsaturated and poly-unsaturated fats as well as carbohydrates. *Even though polyunsaturated fats (vegetable oils) lower HDL (good cholesterol), cause inflammation, and perhaps cancer (14). Furthermore, the governments recommendation for replacing saturated fats with a higher carbohydrate intake can exacerbate the atherogenic dyslipidemia associated with insulin resistance and obesity, increased triglycerides, small LDL particles (the "bad-bad" cholesterol) and reduced HDL ((the "good" cholesterol)16), especially if the carbohydrates are the refined variety.

 It hasn't always been this way. Saturated fats where once a staple of a healthy diet. Our paleolithic ancestors prized animal fat and would preferentially consume it over leaner animal tissue(1). Our great grandfathers and their grandfathers would enjoy cholesterol rich foods such as eggs and bacon daily without thinking twice about their arteries clogging.

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Results: Positive or Anti-atherogenic results:

Total LDL dropped from 111 to 106 mg/dl.

IDL dropped from 17 to 6 mg/dl.

HDL increased from 60 to 76 mg/dl.

HDL2 increased from 17 to 24 mg/dl.

HDL3 increased from 43 to 52 mg/dl.

Total VLDL decreased from 22 to 18 mg/dl.

VLDL3 decreased from 13 to 11 mg/dl mg/dl.

Triglycerides decreased from 100 to 66 mg/dl.

Non-HDL cholesterol decreased from 133 to 124 mg/dl.

Remnant lipoproteins IDL+VLD3 decreased from 30 to 19mg/dl.

Testosterone increased from 586 to 841 ng/dl.

Results: Negative or potentially atherogenic:

Total Cholesterol increased from 192 to 200 mg/dl.

Lipoprotein A increased from 6 to 8 mg/dl.

In summary, the ONLY negative blood marker found could be lipoprotein A, which is one of the "bad-bad" LDL cholesterols increased from 6-8 mg/dl. Total cholesterol did increase by 8 mg/dl but the overall picture of total cholesterol was by all accounts greatly improved. Most significantly, Testosterone increased ~70%, from 586-841 and triglycerides decreased 34%, dropping from 100 to 66. HDL also increased ~27%, from 60 to 76.

Trigylcerides to HDL ("the good cholesterol") ratio has statistically shown to be one of the most potent predictors of heart disease (17, 18), and also all cause mortality (19). A Harvard study found that people with the highest ratio of triglycerides to HDL had 16x the risk of heart attack as those with the lowest ratio. Furthermore, high triglycerides alone increased the risk by 3x. Triglycerides/HDL was found to be a better predictor of heart disease than HDL/LDL and certainly total cholesterol. So in terms of the triglyceride to HDL ratio:

• 2 or less is considered ideal
• 2-4 is at risk
• 4-6 high risk
• 6+ plan a funeral

Our subjects Triglyceride/HDL ratio pre-bacon rich diet was (100/60) or 1.6 which is considered ideal. Post SFA and cholesterol rich diet intervention his ratio improved to 66/76 or .87 which is better than ideal.

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 Read the full article here.

Tip the scales towards plaque reversal

Tip the scales towards plaque reversalThere’s no one easy formula to achieve coronary plaque reversal: no single pill, supplement, food that guarantees that you drop your heart scan score.

But there are indeed factors which can work in favor or against the likelihood that you
gain control over your coronary plaque
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Does everyone who tries to reverse coronary heart disease and reduce their heart scan score succeed? No, not everyone. There are indeed people who fail and see their heart scan score increase. There are usually identifiable and correctable reasons for this to happen. Occasionally, even someone who does everything right still sees their score increase. Thankfully, this is unusual.

There are a number of basic requirements that everybody needs to follow if you hope to gain control over your coronary plaque. There are also less common factors that need to be corrected only by some people. There are also factors that make it more difficult to drop your score.

What makes plaque reversal more likely?

Among the most important facets of the Track Your Plaque program are the recommended targets for conventional lipids: LDL 60 mg/dl, HDL 60 mg/dl, and triglycerides 60 mg/dl: 60-60-60. We call this the Track Your Plaque “Rule of 60”. (Refer to the Special Reports on each of these factors to see how we accomplish this. There’s no quick and dirty pill or supplement that immediately achieves these numbers, but there are indeed effective ways.)

The metabolic syndrome must be eliminated. This usually means weight loss, exercise, and reduction of high-glycemic index foods sufficient to achieve normal blood pressure (preferably 130/80 or less), normal blood sugar (≤100 mg/dl), a C-reactive protein <1.0 g/l. This is also good for your long-term health. The metabolic syndrome is a pre-diabetic condition. You can’t remain pre-diabetic for a lifetime. Unless corrective action is taken, you will convert to a full diabetic. You need to put a stop to this for lots of reasons, including gaining control over coronary plaque .

Lower scores are easier to control than higher scores. A level of 200 or less seems to represent a fairly distinct cut-off between easier and tougher. Having a higher heart scan score of, say 500, doesn’t means it’s impossible, but it will be somewhat tougher and may require a longer period. We’ve seen really high scores in the thousands take 2 to 3 years, for instance.

Taking fish oil. It’s truly shocking how few people take fish oil, even when they’ve suffered a heart attack. It’s simple, virtually harmless, and inexpensive. Yet the benefits are enormous. Fish oil is a crucial requirement for controlling coronary plaque.

Reaching a blood 25-OH-vitamin D3 level of 50 ng/ml. Though our appreciation for this fact is recent, it’s among the most exciting developments in coronary plaque reversal. In fact, we would rank vitamin D as among the most important heart health discoveries of the last 40 years, along with CT heart scanning and fish oil.

Having an optimistic attitude that allows you to see the bright side of problems, overcome difficulties, and engage in healthy relationships with family and friends. Optimists have an easier time in life and they seem to reduce their heart scan scores much more readily.

What makes plaque reversal tougher?

There are some obvious factors that make it less likely that you will drop your heart scan score: cigarette smoking; an unrestricted diet rich in donuts, fried chicken, spare ribs, and cookies; diabetes; uncontrolled high blood pressure; kidney disease. Chances are that, if these factors are uncorrected, you will simply not drop your heart scan score. It is much more likely that your score will increase, sometimes substantially, year after year. Eventually, heart attack or a major heart procedure (actually a lifetime series of procedures) will catch up to you.

More recently, we have seen several well-established diabetics drop their score, sometimes as much as 30%. However, it still remains more difficult if diabetes is part of the picture, as compared to a non-diabetic.

Pre-diabetes represents an intermediate between full-blown diabetes and non-diabetes. However, from a plaque reversal viewpoint, it does make it substantially tougher to drop your score.

Having lipoprotein(a), or Lp(a), also makes it more difficult. We have had more success in halting the increase in heart scan scores (i.e., holding the score steady without increase or decrease) in people with Lp(a), less success in dropping scores. Though our track record with Lp(a) is getting better and better, it still remains a tough nut to crack. With Lp(a), it is clear that you’ve got to work harder to succeed.

Higher scores are tougher to drop than lower scores. Someone with a starting score of, say, 1800, will have to try harder and for a longer period than someone starting with a score of 70. This holds true even if they share the same set of lipoprotein causes. The person with the higher score may even require 2 or 3 years before they see the score stop increasing or decrease, while the person with the lower starting score may drop their score in the first year. People with scores of <100 can even occasionally see zero again. This is not possible (with present-day knowledge) with high scores.

We’ve recently begun to appreciate that a pessimistic attitude may play an important role in your program. People who are angry, critical, see the bad in everything, are isolated and lack social involvement, have a much more difficult time reducing their scores.

Coronary plaque in the balance

In the Track Your Plaque program, we try to help you achieve as many advantages as possible to gain control over coronary plaque. While not perfect, the Track Your Plaque approach is, without question, the most effective program available anywhere.

Obviously, we can do nothing about our genetics, but we can identify and correct as many factors as possible. In this way, we tilt the scales heavily in favor of dropping your heart scan score.

Copyright 2007, Track Your Plaque, LLC
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Krauss is in the HOUSE: 'Low-fat Message Was a MISTAKE'

"Everybody I know in the field -- e v e r y b o d y -- recognized that a simple low-fat message was a mistake," says Dr. Krauss, as interviewed in the latest Men's Health magazine, see below. Why is Men's Health interviewing Krauss?! What is this revolutionary MH reporter saying? Don't. S-W-A-L-L-O-W . . . ! ? ? *haa!!* Men's Health, Your Unstoppable Heart: Before you swallow what your doctor prescribes, we suggest you read this article By: Paul Scott CHOLESTEROL IS A NATURAL SUBSTANCE your body produces for a variety of uses. It is carried through the body in three containers -- LDL, HDL, and VLDL -- that deliver it to cells along with triglycerides. The average man reasons that the cholesterol in his scrambled eggs must surely end up in his arteries somehow, and this makes him do things like order egg-white omelets for breakfast. There is indeed a link between the cholesterol you eat and the cholesterol in your arteries. It's just not the "eat more, have more" worry that's been drummed into you for years. In fact, your body's production and uptake of cholesterol is highly regulated; eat a six-egg omelet and your body simply produces less cholesterol because of the dietary onslaught. "There is a very weak connection between the LDL cholesterol we measure and dietary cholesterol," Dr. Krauss says. "I spend a lot of time talking to reporters and trying to explain that dietary cholesterol is not the same as blood cholesterol." He adds that the 200 milligrams of cholesterol most people eat every day is NOTHING compared with the 800 milligrams their bodies produce [my EMPHASIS]. But you don't have to take his word for it. "It is now acknowledged that the original studies purporting to show a linear relation between cholesterol intake and coronary heart disease may have contained fundamental study design flaws," wrote the author of a recent review in the International Journal of Clinical Practice. [ HERE . Jones PJ citing Hu et al] The author suggests to lower small dense LDL, the actual heart disease culprit Targeting the Killer LDL Small changes, fewer small particles "Small, dense particles of LDL are much more inflammatory than larger particles," says Paul Ziajka, M.D., Ph.D., a clinical lipidologist with the Southeast Lipid Association. Here's how to snuff the little devils. Crack an egg Down an omelet every morning and you may lower your small-particle count, University of Connecticut researchers recently found. People who ate three whole eggs a day for 12 weeks dropped their small-LDL levels by an average of 18 percent. Choose your meds wisely A class of drugs known as fibrates, which includes Tricor, specifically targets small, dense LDL, says Dr. Ziajka. The effect is significant only when your triglycerides are also elevated, he says. [Note: no statin mentioned...*haa*; actually low carb, sat fats and fish oil omega-3 work far FAR better than fibrates, PPAR drugs] Pop some niacin "Most drugs shift particle size after the cholesterol is made," Dr. Ziajka says. "Niacin causes the liver to produce larger particles." Try a no-flush variety (Dr. Ziajka recommends Slo-Niacin) starting with 500 milligrams a day and building to 2,000. There are side effects, so talk to your doctor first. [Note: no-flush doesn't work; slo-niacin is a lower-flush type of niacin] Lighten your load Deflating your spare tire may reduce your small, dense LDL cholesterol, say scientists at Children's Hospital Oakland Research Institute. The majority of overweight men who were pattern B (mostly small LDL) switched to pattern A (mostly large LDL) after they lost an average of 19 pounds. Have a glass That nightly beer does more than relax you -- it may also lower your small, dense LDL, a recent Journal of Clinical Endocrinology Metabolism study found. Men who drank 7 to 13 alcoholic drinks a week had 20 percent fewer small-LDL particles than men who didn't drink at all. [Note: beer aint paleo] Previous animal pharm: Men's Health interview with Mozzafarian MD on benefits of dietary saturated fats Read more about Krauss et al's newest research that redeems the role of saturated fats at my fave peeps and playgrounds: Tourgeman, holymoly ur so funny Nephropal Seth Roberts my Berkeley bud... Animal Fat Peter Hyperlipid Stephan WholeHealthSource Don Primal Wisdom Chris Masterjohn Daily Lipid Dr. Mike Eades THANKGODFORYOURSANENESS

Is Your Bottled Water Killing You? By William Davis, MD

Health Benefits of Magnesium Replacement What can you expect from supplementing magnesium to optimal levels? Research over the past 20 years suggests that magnesium supplementation will accomplish several critically important goals: Magnesium improves insulin sensitivity. Magnesium helps correct impaired insulin sensitivity, the fundamental defect that characterizes pre-diabetes and metabolic syndrome. An intracellular enzyme called tyrosine kinase requires magnesium to allow insulin to exert its blood-sugar-lowering effects. In several studies, daily oral magnesium supplementation substantially improved insulin sensitivity by 10% and reduced blood sugar by 37%.21-23 Magnesium helps correct abnormal lipoprotein patterns. Improved insulin sensitivity from magnesium replacement can markedly reduce triglyceride levels.23 Reduced triglyceride availability, in turn, reduces triglyceride-rich particles, such as very low-density lipoprotein (VLDL) and small low-density lipoprotein (small LDL), both of which are powerful contributors to heart disease.24 Magnesium supplementation can also raise levels of beneficial high-density lipoprotein (HDL).24 Magnesium suppresses abnormal heart rhythms. Magnesium has gained a foothold in hospital care following coronary bypass surgery, when the abnormal heart rhythm known as atrial fibrillation commonly occurs. Magnesium may help suppress this rhythm outside of the hospital as well,25 suggesting a preventive role in averting abnormal heart rhythms. Magnesium reduces blood pressure. Magnesium regulates blood pressure by modulating vascular tone. Magnesium works in ways similar to the prescription hypertension drugs known as calcium-channel antagonists (such as diltiazem and nifedipine), which block calcium channels that trigger constriction of the arteries. Magnesium stimulates the production of prostacyclins and nitric oxide, which are potent artery-relaxing agents.26 Magnesium exerts a modest effect of reducing blood pressure, reflecting its whole-body artery-relaxing properties.27 Magnesium can block migraine headaches. Magnesium has been explored as a means to prevent or relieve migraine headaches. People suffering migraine headaches tend to have lower magnesium levels.28 A study from the State University of New York showed that intravenous magnesium relieved headache symptoms in 15 minutes in 80% of recipients.29 Other studies have since corroborated magnesium’s beneficial effect on migraine headaches, including a trial in children, in which oral supplementation with magnesium oxide reduced the frequency and severity of migraine.30 Magnesium may improve exercise performance. Extensive research in athletes has found that intensive exercise triggers magnesium loss through urinary excretion and perspiration. When magnesium is low, supplementation enhances exercise performance by reducing lactate blood levels (indicating brief, strength-based anaerobic muscle activity), decreasing oxygen requirements, and increasing muscle strength.31,32 Magnesium may benefit many other conditions. Other conditions in which magnesium is believed to exert positive effects include fibromyalgia,33 asthma (acute episodes have been treated successfully with both intravenous and aerosolized magnesium),34 prevention of osteoporosis,35 and premenstrual syndrome.36 Can you correct metabolic syndrome and its complications—such as insulin resistance and high blood pressure—without replacing magnesium? Of course you can, just as you can operate your car without changing the oil. However, magnesium deficiency will catch up with you, and consuming this basic supplement will help you to more easily achieve your health goals. Strategies for Optimizing Your Magnesium Intake According to the US Department of Health and Human Services, nearly all of us fail to achieve even the modest magnesium RDAs of 420 mg for adult males and 320 mg for adult females. Most American adults ingest about 270 mg of magnesium a day, well below the RDA and enough to generate a substantial cumulative deficiency over months and years.37 The magnesium RDA refers to elemental magnesium, defined as the amount of magnesium regardless of its source or form. Magnesium is generally available as various “salts” (not to be confused with table salt), and the amount of elemental magnesium contained in each varies depending on the salt. For example, the amount of magnesium in magnesium oxide is 60%; in magnesium carbonate, 45%; in magnesium citrate, 16%; and in magnesium chloride, 12%.38 Thus, magnesium oxide supplements tend to contain more elemental magnesium per pill than do magnesium citrate supplements. Magnesium salts differ in absorption. Magnesium oxide, though inexpensive and widely available, is thought to be relatively less absorbed than the citrate and chloride forms.39-41 You can also increase your magnesium intake by choosing foods rich in magnesium, which are listed in the table below.42 Foods rich in magnesium (magnesium content in mg) Almonds (1 oz; 24 nuts) 78 Oatmeal (1 cup, cooked) 56 Artichokes (1 cup) 101 Pumpkin seeds (1 oz; 142 seeds) 151 Barley (1 cup, raw) 158 Rice, brown (1 cup, cooked) 84 Beans, black (1 cup, cooked) 120 Soybeans (1 cup, cooked) 148 Beans, lima (1 cup, cooked) 101 Spinach (1 cup, cooked) 163 Brazil nuts (1 oz; 6-8 nuts) 107 Trail mix (1 cup) 235 Halibut (1/2 filet) 170 Walnuts (1 oz; 14 halves) 45 Filberts, hazelnuts (1 oz) 46 Wheat flour, whole grain (1 cup) 166 Oat bran (1 cup, raw) 221 Source: USDA National Nutrient database for Standard Reference, Release17 Dietary Sources of Magnesium Nuts, pumpkin seeds, spinach, and oat bran are particularly rich and healthy sources of magnesium. Another strategy for boosting magnesium intake is to supplement your diet with the soluble fiber known as inulin. Like other soluble fibers, inulin may exert modest cholesterol- and triglyceride-reducing effects. However, it also enhances magnesium absorption in the intestine.43 Inulin can be taken as a supplement, and is contained in some foods (for example, the Stonyfield Farms brand of yogurt). Inulin can help increase satiety (the sense of fullness you get with eating), resulting in decreased calorie intake throughout the day.44 Inulin thus holds promise in supporting efforts to lose weight.45 One more important way to optimize your magnesium intake is to choose water that is rich in magnesium. Unfortunately, in the US, this is easier said than done. The FDA regulates bottled water and mandates that the only additives permitted are fluoride and antimicrobials to deter bacterial growth. Magnesium cannot therefore be added to water labeled spring water or mineral water. Magnesium Content of Mineral Waters The following waters contain far more than the usual amounts of magnesium. Some, like Apollinaris and Pellegrino, are widely available in American grocery stores, while others are found only in upscale groceries or through websites of the water producers. Mineral Water Magnesium Content Original Fountain of Youth Mineral Water (Florida) 609 mg/L Apollinaris (Germany) (410 mg/L of sodium) 130 mg/L Adobe Springs (California and other western states) 110 mg/L Badoit (France) 85 mg/L Colfax (Iowa) 91 mg/L Deep Rock (Colorado) 60 mg/L Evian 24 mg/L Gerolsteiner (Germany) 108 mg/L Noah’s California Spring Water 110 mg/L Pellegrino Sparkling Mineral Water (Italy) (43.6 mg/L of sodium) 55.9 mg/L Manitou Mineral Water (Colorado) 43 mg/L Rosbacher 93 mg/L St. Gero 109.4 mg/L Both Apollinaris and Pellegrino contain more sodium than most other waters, and therefore should be avoided by those who are limiting their sodium intake due to existing hypertension, fluid retention, or kidney disease. Magnesium-rich mineral waters are not easy to find, but they are out there. By FDA definition, mineral waters must contain at least 250 parts per million (ppm) of total dissolved solids. Not all mineral water contains significant quantities of magnesium. For example, Napa Valley’s Calistoga Springs, labeled as “mineral water,” contains 0.61–0.96 mg/L of magnesium, or virtually none. Magnesium Dosage Guidelines The recommended dietary allowance (RDA) for magnesium is 420 mg a day for adult men and 320 mg a day for adult women.46 Most people fail to achieve the RDA, which may lead to magnesium deficiency.37 The most common adverse reaction from the use of magnesium supplements is diarrhea. Other gastrointestinal symptoms include nausea and abdominal cramping. Diarrhea and other gastrointestinal symptoms are less likely to occur if magnesium supplements are taken with food.46 Magnesium supplements are contraindicated in those with kidney failure. Those with myasthenia gravis (an autoimmune disorder that results in progressive skeletal muscle weakness) should avoid magnesium supplements.46 To determine the amount of magnesium contained in bottled water labeled “mineral water” but not listed above, go to the bottler’s website to determine the water’s composition. With the exception of Florida’s Original Fountain of Youth Mineral Water, drinking an entire liter of many so-called mineral waters provides only a modest amount of magnesium. Thus, for instance, if you are currently ingesting around 250 mg a day of magnesium from your diet, drinking a liter of Gerolsteiner a day (supplying 108 mg/L of magnesium) will increase your magnesium consumption only to about 350 mg per day. However, by adding a magnesium supplement that provides as little as 100 mg of elemental magnesium, you will have more than achieved the RDA for an adult male. Since many mineral waters are expensive (around $2-3 per liter), magnesium supplements are a far less costly way to optimize your magnesium intake. Conclusion The intensification of municipal water treatment has resulted in a growing epidemic of magnesium deficiency, with most Americans failing even to achieve the modest levels set by the government-recommended RDA. Most of us have daily deficiencies in magnesium intake of only 70-200 mg a day. The consequences of magnesium deficiency can be dramatic, including poor insulin response, migraine headaches, high blood pressure, and abnormal and even dangerous heart rhythms. Fortunately, there are plenty of healthy choices—foods rich in magnesium, low-cost magnesium supplements, and waters rich in magnesium—that can you help reach or exceed the magnesium RDA and attain the numerous health benefits conferred by optimal magnesium intake. Dr. William Davis is an author and cardiologist practicing in Milwaukee, WI. He is founder of the Track Your Plaque program, a heart disease prevention and reversal program that shows how CT heart scans can be used to track and control coronary plaque. He can be reached at www.TrackYourPlaque.com. The Basics of Water and Water Purification While the Environmental Protection Agency regulates the quality of tap water, the Food and Drug Administration (FDA) is responsible for regulating bottled water. In 1995, the FDA issued its most recent regulations classifying various waters: Artesian well water is water that naturally flows upward from an underground aquifer to a well, without the need for pumping. Mineral water is water from an underground source that contains at least 250 parts per million (ppm) of dissolved solids consisting of minerals and trace elements. Mineral content of 250-500 ppm is often called “low mineral content” or “light mineral water,” while content of 1500 ppm or greater is “high mineral content.” (In Europe, spring waters with dissolved solids equal to or less than 500 mg/L are considered “mineral with low mineral content” or simply “mineral water.”) Minerals and trace elements cannot be added artificially to water labeled as mineral. Spring water, like artesian well water, comes from an underground source but flows naturally to the earth’s surface. It cannot come from a public or municipal source. Spring water must be collected directly at the spring or through a borehole tapping the underground source. Mineral content is less than 250 ppm and cannot be added after collection. Well water is water from a hole bored or drilled into the ground, which taps into an aquifer and is drawn to the surface using a pump. Many homes in the US that do not have access to municipal water use well water. To make matters even more complicated, any water—regardless of the source—can be treated or filtered. This is usually done to modify its taste or to remove undesirable ingredients. Methods of treatment are defined as: Distillation. Water is vaporized and collected, leaving behind any solid residues, including minerals. Distilled water contains no minerals whatsoever. Reverse osmosis. In this common water-purifying process, water is forced through membranes to remove minerals in the water. Deionization. Also called demineralization or ion exchange, this process uses synthetic resins to remove ions and minerals from water. This is very effective at removing ionized impurities, but does not remove organic, bacterial, pathogenic, or particulate matter efficiently. Deionized water contains no magnesium. Absolute 1 micron filtration. Water is passed through filters that remove particles larger than 1 micron in size, including Cryptosporidium, a parasite that causes intestinal infestation. This process does not affect the water’s mineral content. Ozonation. Many bottled water companies use this process instead of chlorine to rid water of bacteria. Ozonation does not affect the mineral content of water. Many bottled waters are simply tap water processed using one or more of the above processes of distillation, reverse osmosis, deionization, or filtration. This leaves the water virtually devoid of both nutrients and contaminants. Of the 700 or so brands of bottled water available in the US, 80% are processed water. Many experts say that treated water like this is virtually identical to that produced by home water purifiers. The appeal of these waters is therefore a reduction in impurities like lead and pesticide residues, or better taste—but not enhanced mineral content. Bottled processed waters contain little or no magnesium. It should also be noted that unlike tap water, purified waters and water purifiers reduce or eliminate the fluoride that is added by many municipal treatment facilities to promote dental health. Although the FDA permits producers to add it back to purified water, few actually do. Waters derived from natural sources like artesian well water, well water, mineral water, and spring water are generally slightly richer in mineral content than are processed and tap waters. However, the difference is small. Nearly all American bottled waters obtained from natural sources—whether artesian, well, spring, or mineral waters—contain less than 6 ppm of magnesium, a trivial amount.

References

1. Available at: http://www.historyofwaterfilters.com/. Accessed November 14, 2006. 2. Azoulay A, Garzon P, Eisenberg MJ. Comparison of the mineral content of tap water and bottled waters. J Gen Intern Med. 2001 Mar;16(3):168-75. 3. Available at: http://lpi.oregonstate.edu/infocenter/minerals/magnesium/index.html. Accessed November 14, 2006. 4. Touyz RM. Magnesium in clinical medicine. Front Biosci. 2004 May 1;9:1278-93. 5. Liebscher DH, Liebscher DE. About the misdiagnosis of magnesium deficiency. J Am Coll Nutr. 2004 Dec;23(6):730S-1S. 6. Durlach J, Bac P, Durlach V, et al. Magnesium status and ageing: an update. Magnes Res. 1998 Mar;11(1):25-42. 7. Eisenberg MJ. Magnesium deficiency and sudden death. Am Heart J. 1992 Aug;124(2):544-9. 8. Dacey MJ. Hypomagnesemic disorders. Crit Care Clin. 2001 Jan;17(1):155-73, viii. 9. Eisenberg MJ. Magnesium deficiency and cardiac arrhythmias. NY State J Med. 1986 Mar;86(3):133-6. 10. Purvis JR, Movahed A. Magnesium disorders and cardiovascular diseases. Clin Cardiol. 1992 Aug;15(8):556-68. 11. Smetana R, Stuhlinger HG, Kiss K, Glogar DH. Intravenous magnesium sulphate in acute myocardial infarction—is the answer “MAGIC”? Magnes Res. 2003 Mar;16(1):65-9. 12. Kousa A, Havulinna AS, Moltchanova E, et al. Calcium:magnesium ratio in local groundwater and incidence of acute myocardial infarction among males in rural Finland. Environ Health Perspect. 2006 May;114(5):730-4. 13. Anderson TW, Le Riche WH, MacKay JS. Sudden death and ischemic heart disease. Correlation with hardness of local water supply. N Engl J Med. 1969 Apr 10;280(15):805-7. 14. Available at:http://www.nsf.org/international/press_release.asp?p_id=12041. Accessed November 14, 2006. 15. Laires MJ, Monteiro CP, Bicho M. Role of cellular magnesium in health and human disease. Front Biosci. 2004 Jan 1;9:262-76. 16. Berkelhammer C, Bear RA. A clinical approach to common electrolyte problems: 4. Hypomagnesemia. Can Med Assoc J. 1985 Feb 15;132(4):360-8. 17. Roffe C, Sills S, Crome P, Jones P. Randomised, cross-over, placebo controlled trial of magnesium citrate in the treatment of chronic persistent leg cramps. Med Sci Monit. 2002 May;8(5):CR326-30. 18. Bilbey DL, Prabhakaran VM. Muscle cramps and magnesium deficiency: case reports. Can Fam Physician. 1996 Jul;42:1348-51. 19. Bussone G. Pathophysiology of migraine. Neurol Sci. 2004 Oct;25 Suppl 3S239-41. 20. He K, Liu K, Daviglus ML, et al. Magnesium intake and incidence of metabolic syndrome among young adults. Circulation. 2006 Apr 4;113(13):1675-82. 21. Guerrero-Romero F, Tamez-Perez HE, Gonzalez-Gonzalez G et al. Oral magnesium supplementation improves insulin sensitivity in non-diabetic subjects with insulin resistance. A double-blind placebo-controlled randomized trial. Diabetes Metab. 2004 Jun;30(3):253-8. 22. Rodriguez-Moran M and Guerrero-Romero F. Oral magnesium supplementation improves insulin sensitivity and metabolic control in type 2 diabetic subjects: a randomized double-blind controlled trial. Diabetes Care. 2003 Apr;26(4):1147-52. 23. Yokota K, Kato M, Lister F, et al. Clinical efficacy of magnesium supplementation in patients with type 2 diabetes. J Am Coll Nutr. 2004 Oct;23(5):506S-9S. 24. Rasmussen HS, Aurup P, Goldstein K, et al. Influence of magnesium substitution therapy on blood lipid composition in patients with ischemic heart disease. A double-blind, placebo controlled study. Arch Intern Med. 1989 May;149(5):1050-3. 25. Piotrowski AA, Kalus JS. Magnesium for the treatment and prevention of atrial tachyarrhythmias. Pharmacotherapy. 2004 Jul;24(7):879-95. 26. Sontia B, Touyz RM. Role of magnesium in hypertension. Arch Biochem Biophys. 2006 May 24. 27. Jee SH, Miller ER, III, Guallar E, et al. The effect of magnesium supplementation on blood pressure: a meta-analysis of randomized clinical trials. Am J Hypertens. 2002 Aug;15(8):691-6. 28. Gallai V, Sarchielli P, Morucci P, Abbritti G. Magnesium content of mononuclear blood cells in migraine patients. Headache. 1994 Mar;34(3):160-5. 29. Mauskop A, Altura BT, Cracco RQ, Altura BM. Intravenous magnesium sulfate rapidly alleviates headaches of various types. Headache. 1996 Mar;36(3):154-60. 30. Wang F, Van Den Eeden SK, Ackerson LM, et al. Oral magnesium oxide prophylaxis of frequent migrainous headache in children: a randomized, double-blind, placebo-controlled trial. Headache. 2003 Jun;43(6):601-10. 31. Lukaski HC. Magnesium, zinc, and chromium nutrition and athletic performance. Can J Appl Physiol. 2001;26 SupplS13-S22. 32. Cinar V, Nizamlioglu M, Mogulkoc R. The effect of magnesium supplementation on lactate levels of sportsmen and sedanter. Acta Physiol Hung. 2006 Jun;93(2-3):137-44. 33. Sarac AJ, Gur A. Complementary and alternative medical therapies in fibromyalgia. Curr Pharm Des. 2006;12(1):47-57. 34. Blitz M, Blitz S, Hughes R, et al. Aerosolized magnesium sulfate for acute asthma: a systematic review. Chest. 2005 Jul;128(1):337-44. 35. Rude RK, Gruber HE. Magnesium deficiency and osteoporosis: animal and human observations. J Nutr Biochem. 2004 Dec;15(12):710-6. 36. Rapkin A. A review of treatment of premenstrual syndrome and premenstrual dysphoric disorder. Psychoneuroendocrinology. 2003 Aug;28 Suppl 3:39-53. 37. Ervin RB, Wang CY, Wright JD, Kennedy-Stephenson J. Dietary intake of selected minerals for the United States population: 1999-2000. Adv Data. 2004 Apr 27;(341):1-5. 38. Available at: http://ods.od.nih.gov/factsheets/magnesium.asp#h6. Accessed November 15, 2006. 39. Firoz M, Graber M. Bioavailability of US commercial magnesium preparations. Magnes Res. 2001 Dec;14(4):257-62. 40. Coudray C, Rambeau M, Feillet-Coudray C, et al. Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach. Magnes Res. 2005 Dec;18(4):215-23. 41. Walker AF, Marakis G, Christie S, Byng M. Mg citrate found more bioavailable than other Mg preparations in a randomised, double-blind study. Magnes Res. 2003 Sep;16(3):183-91. 42. Available at: http://www.nal.usda.gov/fnic/foodcomp/Data/SR14/wtrank/sr14w304.pdf. Accessed November 15, 2006. 43. Roberfroid MB. Introducing inulin-type fructans. Br J Nutr. 2005 Apr; 93 Suppl 1S13-S25. 44. Archer BJ, Johnson SK, Devereux HM, Baxter AL. Effect of fat replacement by inulin or lupin-kernel fibre on sausage patty acceptability, post-meal perceptions of satiety and food intake in men. Br J Nutr. 2004 Apr;91(4):591-9. 45. Hoeger WW, Harris C, Long EM, Hopkins DR. Four-week supplementation with a natural dietary compound produces favorable changes in body composition. Adv Ther. 1998 Sep-Oct;15(5):305-14. 46. Available at: http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/mag_0167.shtml. Accessed November 16, 2006.

Dr John Briffa on ezetimibe (Zetia)

More bad news for the makers (and takers) of cholesterol-reducing drug ezetimibe (Zetia) http://www.drbriffa.com

Posted By Dr John Briffa On November 16, 2009

Previously, I have written about the drug combination of simvastatin and ezetimibe (sold as Vytorin in the US). Both of these drugs reduce cholesterol, but through different mechanisms. Taken together, these drugs do do a good job of reducing cholesterol levels And we all know that the lower we get the cholesterol levels down the better, right? Well, actually, results show that Vytorin [1] did not work to halt the progression of the ‘plaques’ that gum up arteries and can precipitate heart attacks and strokes.

And then another thing is that giving people simvastatin and ezetimibe is associated with an increased risk of [2] death due to cancer. This finding was inexplicably waved away by scientists as a [3] chance finding (even though the statistics showed that the finding was very unlikely to be due to chance).

Anyway, this week sees more bad news for the manufacturers of Vytorin and also those who take it. The New England Journal of Medicine has just published a study in which individuals on a statin were additionally treated with ezetimibe or niacin (vitamin B3) over 14 months [1]. All of the individuals in the trial had either been diagnosed with heart disease or were deemed to be at high risk of this condition.

The researchers measured a number of parameters including:

LDL-cholesterol (a form of cholesterol said to be associated with a higher risk of cardiovascular disease)

HDL-cholesterol (a form of cholesterol said to be associated with a lower risk of cardiovascular disease)

Triglyceride levels (a form of blood fat said to be associated with higher risk of cardiovascular disease)

Carotid artery intima thickness (the thickness of the wall of the major blood vessel supplying blood to the head – increased thickness is generally taken as a sign of worsening cardiovascular disease risk)

In the group taking a statin and ezetimibe, LDL, HDL and triglyceride levels went down.

In the group taking a statin and niacin, LDL and triglyceride levels went down, and HDL levels went up.

On paper, at this point, the group taking the niacin and statin fared better. However, more important than these results were those relating to the carotid artery intima thickness. Guess what? The group taking the niacin did better than the group taking ezetimibe on this score too.

One other outcome the researchers kept tabs on was ‘major cardiovascular events’ such as heart attacks and strokes. Here again, the niacin group fared better – 1 per cent of them had such an event compared to 5 per cent in the group taking ezetimibe.

The New York Times reports [4] here that Dr Peter Kim, the president of Merck Research Laboratories (makers of ezetimibe) claimed that the study was limited because it did not compare the groups of patients taking a statin and a second drug to a placebo group. He also claims that a drug’s ability to improve artery-wall thickness has not been proved to automatically correlate with a reduction in heart attacks. Moreover he stated that ezetimibe lowers bad cholesterol and lowering bad cholesterol is a “known good”.

Ezetimibe has been licenced on the basis of its ability to reduce LDL-cholesterol – something that is referred to as a ‘surrogate marker’. So, Merck it seems that Merck is happy for its drug to be sold and promoted on the basis of one surrogate marker (reduced cholesterol), but none-too-keen for its drug to be criticised on the basis of another surrogate measure (carotid artery intima thickness).

Dr Kim also describes a reduction in bad (LDL) cholesterol as a “known good”. However, the new England Journal of Medicine study found that lower levels of LDL cholesterol were actually associated with an increase in carotid artery intima thickness. And never mind this, do we really think that just because something reduces LDL cholesterol levels, that has to be a good thing. I mean, if arsenic and cyanide were found to reduce LDL cholesterol levels, would that mean we should all be taking arsenic and cyanide every day?

The New York Times article also quotes Dr James Stein, professor at the University of Wisconsin medical school, who points out that as far as ezetimibe is concerned, “there is not a shred of evidence that it does anything good for blood vessels or heart disease.”

References:

1. Taylor AJ, et al. Extended-Release Niacin or Ezetimibe and Carotid Intima–Media Thickness NEJM 15th November 2009 [epub ahead of print]


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Article printed from Dr Briffa’s Blog: http://www.drbriffa.com

URL to article: http://www.drbriffa.com/blog/2009/11/16/more-bad-news-for-the-makers-and-takers-of-cholesterol-reducing-drug-ezetimibe-zetia/

URLs in this post:
[1] did not work: http://www.drbriffa.com/blog/2008/01/28/trial-results-forced-out-of-drug-company-support-the-concept
-that-cholesterol-may-not-cause-cardiovascular-disease/

[2] death due to cancer: http://www.drbriffa.com/blog/2008/07/23/cholesterol-lowering-combination-found-to-have-limited-benef
it-again-and-now-is-linked-with-increased-risk-of-cancer/

[3] chance finding: http://www.drbriffa.com/blog/2008/09/03/is-it-right-for-scientists-to-put-the-links-between-choleste
rol-reducing-medication-and-cancer-down-to-chance/

[4] here: http://www.nytimes.com/2009/11/16/health/research/16heart.html