Wednesday, January 27, 2010

When the Brain Is Hungry For Cholesterol

by Chris Masterjohn

Those of you who have spent much time perusing my web site know that cholesterol is the limiting factor for the formation of synapses, connections between neurons that form the basis of learning and memory. In fact, one of the reasons we learn better when we get enough sleep is because the brain ramps up its production of cholesterol when we're getting our shut-eye.

Scientists have long thought that cholesterol in the plasma never enters the brain in significant amounts because its transport is blocked by the blood-brain barrier. In general, the brain produces its own cholesterol and, when that cholesterol's time is up the brain converts it to 24-hydroxy-cholesterol and sends it out with the trash.

An article in
February's issue of Current Opinion in Lipidology, however, reviews two recent studies published last year showing that when the brain fails to make enough of its own cholesterol, it does in fact take it from the bloodstream.

In one study, researchers inactivated the gene for squalene synthase, the first enzyme committed to
cholesterol synthesis, from the cells in the ventricular zone of the brains of mice. Progenitor cells in this region began producing new blood vessels that allowed them to acquire cholesterol from the bloodstream or from the neural tube.

In the other study, researchers inactivated a cholesterol transporter in glial cells. Glial cells support neurons in a variety of ways — one of them is to produce secretions rich in the
cholesterol necessary for synapse formation. The brains of these mice partly made up for the resulting cholesterol deficiency by taking up more cholesterol esters from HDL particles in the bloodstream.

This concept, that when cholesterol made in the brain proves insufficient to meet the brain's needs the brain can compensate by taking cholesterol from the blood, goes a long way in explaining why all of the mental problems suffered by Smith-Lemli-Opitz Syndrome (SLOS) patients improve with dietary cholesterol. In fact, the FDA has even approved a pharmaceutical-grade cholesterol supplement to improve the retardation, hyperactivity, irritability, poor attention span, and tendency toward aggressive and self-injuring behavior seen in these children. 

These findings are truly remarkable, because they open up the possibility that cholesterol in the bloodstream may support the brain in much less extreme cases of cholesterol deficiency and in many other undiscovered ways.

Read more about the author, Chris Masterjohn, PhD, here.

Monday, January 25, 2010

What to Eat? Check Your Blood Sugar

by Chris Masterjohn

Dr. William Davis is a practicing cardiologist in Milwaukee, Wisconsin. He publishes interesting thoughts and practical advice on his Heart Scan Blog. Recently, he suggested measuring your blood sugar one hour after meals in order to determine what foods are best for you. Meals that result in a blood sugar under 110 mg/dL one hour after eating are best. You can read the full blog here.

This makes a lot of sense to me, because there is great variation between individuals in the glycemic index of different foods. It could also indentify foods that put your body under stress.

I went to a seminar last year given by someone who had done research contributing to the development of a glycemic index (GI) database, and she concluded that the interindividual variation was so great that the index is almost useless. 

The GI compares the rise in blood glucose after eating a food to the rise in blood glucose after consuming pure glucose. Generally, the GI is expressed as some percentage less than 100 because the body takes more time to break starches down into glucose or convert amino acids to glucose than it does to simply transport glucose from the intestines into the blood. However, in one case the researcher presented on, an individual had a much stronger rise in blood glucose after consuming white bread than after consuming glucose! Clearly, this person was not just breaking the bread down into glucose but also releasing stress hormones into his blood that would further rise his glucose levels by breaking down stored glycogen and converting his own protein into sugar. He may have been unaware of his adverse reaction to white bread, but it may have been doing damage to his body all along.

The $20 investment in a blood sugar monitor that Dr. Davis recommends may thus prove a useful investment for helping to determine your ideal diet.

Read more about the author, Chris Masterjohn, PhD, here.

Friday, January 22, 2010

The Importance of Humility in Science -- A Philosophical Musing For the Weekend

by Chris Masterjohn

Socrates once said, "All I know is that I know nothing." Centuries later, St. Paul, the great expounder of Christian theology, ethics, and mysticism, said that "any man who says he knows something does not yet know as he ought."

A very wise faculty member and department head of a science program I once spoke with told me that the more we learn as scientists the more we learn how little we know, and that he tells all his PhD students when they graduate to never brag about what they know but to go out into the world bragging about how little they know.
This type of humility is essential to science. Not simply to avoid the arrogance that often comes with knowledge, but because our understanding of the world around us often is, in fact, much more limited than we realize or want to believe.

In quantum mechanics, Werner Heisenberg (1901-1976) offered the Heisenberg Uncertainty Principle. Heisenberg showed that we cannot simultaneously determine an electron's position and momentum. The more we study the position, the less able we are to determine the momentum; the more we study the momentum, the less able we are to determine the position.

There is a similar principle that exists in nutrition. The greater the certainty with which we can determine cause and effect, the less certain we can be that our knowledge pertains to the real world. The more certain we are that our knowledge pertains to the real world, the lesser the certainty with which we can determine cause and effect.

Consider for a moment the "gold standard" of evidence for nutritional and medical treatments: the randomized controlled trial. It takes place, at least in part, in a laboratory or hospital setting. The subjects know they are being studied. They know they are receiving some type of treatment or placebo. They are getting their blood drawn. If we really want to understand cause and effect, the subjects may have to be placed in a metabolic ward, where their exercise and food intake is strictly controlled.

If the treatments really need placebos, this alone is a profound admission that every aspect of the study has a psychological impact with physiological consequences. Are the patients thinking the same things? Feeling the same way? Doing the same fun things, the same boring things? No. They may be bothered by blood drawings; they may be hopeful about treatments. They may be analyzing how they eat and exercise more closely. They may be conforming their behavior to the expectations of physicians and scientists.

Is the nutritional or medical treatment that proves effective within this type of setting effective in the real world? Is the one proven ineffective under this model without any effect in the real world? We simply don't know, and can't prove it one way or the other.

If we wish to study with great precision the detailed mechanisms of cause and effect, we turn to studying cells isolated in a petri dish, or we react molecules with molecules in a test tube. We thus establish with great certainty the laws of biochemical reactions but must then begin asking, to what extent does a test tube approximate the living environments within which such biochemicals ordinarily find themselves? To what extent does bathing a cell in a compound approximate the effect of eating it? Do immortalized, usually cancerous, cells behave the same way in a petri dish as normal, healthy cells behave as part of human tissue?
Consider, on the other hand, the observational study. Scientists observe free-living people doing what they would ordinarily do. In some cases the people may be enrolled in a study while in other cases they may not even know they are being studied. In these cases, we can be highly confident that the truths we obtain are applicable to the real world because it is that real world we are studying. Yet at the same time we lose our ability to determine cause and effect. 

When all of the different types of evidence agree with each other, we may become more confident that we have discovered a universal truth. But there is always a degree of uncertainty underlying the knowledge we obtain in the field, and the more closely we study a phenomenon, the more we risk distorting it.

The job of the scientist is, of course, to develop models of studying phenomena that produce the least distortion of the real phenomenon. But the scientist also must exercise a healthy dose of humility, and admit that her or his knowledge is but a drop in the ocean of truth.

Read more about the author, Chris Masterjohn, PhD, here.

Thursday, January 21, 2010

The Journal of the American Medical Association Finally Questions Whether the FDA Should be Approving Useless No-Evidence Cholesterol-Lowering Drugs

by Chris Masterjohn

After the Coronary Primary Prevention Trial, fittingly published in 1984, showed that cholestyramine, a drug that lowers cholesterol by causing its conversion to bile acids, could reduce the risk of heart attacks, cholesterol was widely villainized as a killer. From then on, the decades-old campaign of the American Heart Association against eggs and butter was vindicated in the press and the FDA began considering any drug that could effectively reduce cholesterol levels in the blood to be a preventer of heart attacks.

In truth, however, the evidence suggests that cholestyramine, while increasing the risk of dying from other diseases, lowers the risk of heart attacks not by lowering "cholesterol" but by clearing LDL from the bloodstream more quickly and thus reducing its interactions with free radicals that can oxidize, nitrate, and glycate it. Thus, the liver takes up healthy LDL and the immune system does not need to come and clean up the mess made by the toxic, damaged LDL. When the immune system has to come clean up such a mess, it forms arterial plaques.

For more information, see
"High Cholesterol and Heart Disease — Myth or Truth?"

Nevertheless, the medical community has gone gung-ho not over reducing damage to LDL particles, but over lowering levels of LDL-associated cholesterol.

Thus when ezetimibe was released, a drug that suppresses absorption of dietary cholesterol, the FDA did not ask whether ezetimibe reduces oxidation, nitration, or glycation of LDL, nor did it ask whether ezetimibe can be proven to prevent heart attacks. Instead, it simply approved the drug as prevention for heart disease based on the sole evidence that it lowers cholesterol.

recent study in the New England Journal of Medicine, however, strongly suggested that ezetimibe does nothing to prevent heart disease. It compared the use of a statin plus ezetimibe to the use of a statin plus the B vitamin niacin. While the ezetimibe combination was 70% more effective at lowering cholesterol than the niacin combination, the level of atherosclerosis diminished in the niacin group and actually increased in the eztimibe group.

This came on the heels of two studies (SEAS and ENHANCE) published in 2008 showing that combining a statin with ezetimibe instead of a placebo had no effect on atherosclerosis or heart attacks, despite lowering LDL-cholesterol.

Mike Mitka, senior staff writer for the Journal of the American Medical Association (JAMA), finally
asked some critical questions in this month's issue of JAMA:

Should the FDA be approving drugs (especially those that represent new classes of medications) that satisfy established surrogate markers without demanding immediate postmarketing studies to prove clinical effectiveness? Why are physicians continuing to prescribe a drug whose clinical effectiveness has yet to be shown? And why are not more patients receiving niacin, with its proven effectiveness as an adjunct therapy to statins?
Merck makes $4 billion per year from the 9 million people taking ezetimibe alone or an ezetimibe/statin combination.

The FDA approved the drug in 2002. In 2005, the first large outcome trial began. Its results will be available in 2015. If its results are anything like the three smaller trials that have been published recently, physicians may stop prescribing it. In the mean time, Merck will make a whole lot of money.

At least writers in the top medical journals are beginning to ask the tough questions. It's a start.

Read more about the author, Chris Masterjohn, PhD, here.

Tuesday, January 19, 2010

When Glucose Makes a Mess

by Chris Masterjohn

In my Cholesterol Podcast on the Livin' La Vida Low-Carb Show with Jimmy Moore, I offered the view that atherosclerosis and many other degenerative diseases can be seen as a process of oxidative damage wherein polyunsaturated fatty acids (PUFAs) get damaged by toxins, heavy metals, and byproducts of normal metabolism, break into pieces, and then continue to damage other molecules. I suggested thinking of this as breaking a glass on the floor — the glass breaks into shards, and then becomes dangerous. Step on the shards, and your foot will bleed. Likewise, when proteins, DNA, and other important molecules come into contact with "the pieces of broken PUFAs" they get seriously hurt.

PUFAs are not the only molecules subject to this type of damage. "Oxidative stress" is very similar to and very related to "nitrative stress" and "carbonyl stress." "Carbonyl stress" involves the breakdown products of sugars.

Monday, January 18, 2010

Weston Price's Activator X -- Cure for Cancer?

by Chris Masterjohn

Those of you reading The Daily Lipid from my web site, Cholesterol-And-Health.Com might also be interested in reading my other blog on the Weston A. Price Foundation's web site, Mother Nature Obeyed. The title is taken from the conclusion with which Price ended his epic work Nutrition and Physical Degeneration: "Life in all its fullness is mother nature obeyed."

You can read the first post here:

Cure For Cancer: Activator X May Be the Missing Link

My posts to The Daily Lipid will be brief but frequent; I'll be posting to the "MNO Blog" about once every two weeks, with a more comprehensive view on a given topic. I hope you enjoy the first post — more will be on the way!

Read more about the author, Chris Masterjohn, PhD, here.

Friday, January 15, 2010

Saturated Fat Is Not Associated With CVD, Evidence of Publication Bias

by Chris Masterjohn

A recent meta-analysis in the American Journal of Clinical Nutrition pooled together data from 21 unique studies that included almost 350,000 people, about 11,000 of whom developed cardiovascular disease (CVD), tracked for an average of 14 years, and concluded that there is no relationship between the intake of saturated fat and the incidence of heart disease or stroke. In fact, the "risk ratio" for the development of CVD as intake of saturated fat increased was 1.0, meaning that people who ate more saturated fat were no more or less likely to develop CVD.

The authors also used a funnel plot to show that smaller studies more prone to error were more likely to show an association between saturated fat intake and CVD than were larger studies less prone to error. 

In the picture below, each square or diamond represents a study. If it is to the right of the vertical line down the middle, it reported an increase of CVD risk with increased intake of saturated fat. If it is to the left of the vertical line, it reported a decrease in risk. The studies plotted towards the top were larger and the studies plotted toward the bottom were smaller.

If there is no publication bias, we would expect the studies to be distributed symmetrically around the average result of the total pooled data (in this case, a risk ratio of 1.0, meaning no effect). Publication bias tends to affect smaller studies — everyone wants to know the results of large, expensive, extensively publicized studies, but small studies will often go unpublished or ignored if they have negative results. In the picture, you can see that the smaller studies were greatly skewed towards finding an increase in CVD risk with increased intake of saturated fat, while the larger studies were more likely to find no effect. 

This does not prove, but suggests, that many small studies went unpublished or otherwise lost down the memory hole if they found no association or a negative association between intake of saturated fat and risk of CVD.

All in all, however, we must remember that correlation never demonstrates causation. As I will be discussing in the upcoming sequel to my
PUFA Report, the controlled intervention trials substituting polyunsaturated fats for saturated fats suggested that replacing foods like butter with foods like vegetable oil would increase the risk of cancer and possibly even hasten the development of atherosclerosis.

It will be interesting to see how extensively the media publicizes this analysis — or will it be ignored?

Read more about the author, Chris Masterjohn, PhD, here

Thursday, January 14, 2010

The Federal Reserve and the War on Health Freedom

by Chris Masterjohn

I made some important changes to my article, "The Federal Reserve and the War on Health Freedom."

The Federal Reserve is a privately owned but partially government-controlled institution with the exclusive legal right to create money — an act called "counterfeiting" when anyone else does it and that would qualify anyone else for a prison sentence. In the original version of my article, however, I stated that the Fed "profits" from this activity. In actuality, it turns most of these profits back to the government. I have since revised that section to more accurately describe what happens — the creation of money transfers real wealth from the people who earned it to banks and politically favored corporations.

The new text of
that section follows below.

Federal Reserve Inflation — Stealing From the Poor and Middle Class

Centuries ago, gold smiths began holding gold for people and giving them receipts of ownership so they could come back at any time and retrieve the gold. They found, however, that they could make far more profit if they gave out receipts for gold that did not exist. Only a few people at any given time would come back to redeem their receipts for gold, so no one would notice.

Any rational person would call this fraud. But this is what our banks do today, and we call it "fractional reserve banking." Only today our banks are holding reserves of cash instead of gold and lending out more digital money than they have. The Federal Reserve, for its part, simply creates electronic money credits on a computer. The money comes out of nowhere as if by magic, and leaks into the economy.

How does that affect you and me? Simple. The more dollars there are chasing the same number of goods and services, the less and less our dollar is worth.

So if we have less wealth, where does the wealth go? After all, money is not wealth; it just purchases wealth. So where does the actual wealth — goods and services and control over productive capital — go?

The wealth simply gets shifted from the people who earned it to certain politically favored industries.

While the Federal Reserve is able to generate digital money out of thin air, it is required to turn most of the profit back to the government. For example, Fortune reported that the Fed made $52 billion in profits in 2009 but returned $46 billion back to the government, using $4.6 billion to shore up its own capital and paying out only $1.4 billion as dividends to its private owners. So the Federal Reserve itself does not significantly profit from the system.

The first to rake in large profits are the banks, because when the Federal Reserve pumps newly created money into their accounts, they are allowed to create ten-fold more. Moreover, by acting as a "lender of last resort," the Fed stabilizes the entire institution of fractional-reserve banking. Ordinarily, it would not be safe for banks to lend out ten times more money than they have, but if the Fed can be counted on to prop up the system, banks can make huge profits without the natural risk such fraudulent business would otherwise entail.

The other major profiteers are the corporations favored by the government and the Federal Reserve who get to use the money first. If Congress borrows money from the Federal Reserve to pay for the cholesterol-lowering statin drugs included in the prescription drug plan passed a few years ago, then those pharmaceutical companies get to spend the money first while it still has all its present value. Then, as the money slowly trickles through the economy eventually making its way into your paycheck, it loses its value.

So wealth is transferred from people who earn it to banks, corporations with government contracts, and corporations that conduct transactions directly with the Federal Reserve.

Read more about the author, Chris Masterjohn, PhD, here.

Wednesday, January 13, 2010

Cholesterol Podcast -- Chris Masterjohn on the Livin La Vida Low-Carb Show with Jimmy Moore

by Chris Masterjohn

If you missed this on December 14, you can still listen now!

Chris Masterjohn on the Health Benefits of Cholesterol — Espisode 314

Read more about the author, Chris Masterjohn, PhD, here

Corn Oil, Not "High-Fat," Causes Inflammation

by Chris Masterjohn

According to a recent article on the Science Daily site, "High Fat Diet Increases Inflammation in the Mouse Colon," a November 2009 study published by researchers from Rockefeller University showed that a diet "high in fat and low in fiber, vitamin D and calcium" triggered an inflammatory process that could lead to cancer in the colons of laboratory mice. The article quoted Peter Holt, one of the authors of the paper, as saying that the study lent support to the hypothesis that "red meat, processed meat and alochol can increase risk of colorectal cancer."

One would think that a study designed to test the hypothesis that fat from red meat could trigger inflammation or cancer would use the type of fat found in red meat — a roughly even mix of saturated and monounsaturated fats. However, the fat used in
the study came entirely from corn oil. Corn oil is 56% polyunsaturated fatty acids (PUFAs), 98% of which are omega-6 fatty acids, mostly linoleic acid. By contrast, red meat is less than 3% polyunsaturated fatty acids.

As I've written about in my article,
"High Cholesterol and Heart Disease — Myth or Truth?" and in my "PUFA Report Part I: How Essential Are the Essential Fatty Acids?" polyunsaturated fats are uniquely vulnerable to oxidative stress, a condition where molecules rip electrons apart from other molecules, often breaking them into pieces or sticking to them and destroying their functionality.

Mice, unlike humans, can synthesize their own vitamin C. After six months on the high-PUFA corn oil diet, mice had increased levels of vitamin C, which probably protected them from some of the effects of oxidative stress. The master antioxidant of the cell, glutathione, is made from three amino acids, the most important of which is cysteine. After six months on the high-PUFA diet, the mice had higher proportions of their glutathione in the oxidized state and major depletions in the amino acid cysteine and its precursor methionine.

The medical and nutritional establishments in this country used to recommend corn oil but quietly withdrew this recommendation after the LA Veterans Administration Hospital Study showed that replacing butter with polyunsaturated vegetable oils over the course of a long-term double-blind study increased the risk of cancer. Apparently elements of these establishments have no problems continuing to perform studies with corn oil while blaming the effects on "red meat, processed meat and alcohol."

But such is the difference between PR and science.

Read more about the author, Chris Masterjohn, here.