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The Cholesterol Times, Issue #009 -- Low Cholesterol, Violent Suicide, and the Policosanol Scam
May 27, 2006
|A Publication of Cholesterol-And-Health.com
Issue #009, May 28, 2006
After seven months off, it's great to be back writing another issue of The Cholesterol Times!
Since the last issue, hundreds of people have joined the newsletter. If you're one of them, welcome aboard!
In the meantime, I've written a massive refutation of the idea that moderate intakes of preformed vitamin A from animal foods contribute to osteoporosis for the Weston A. Price Foundation. This was published in the Spring edition of Wise Traditions, and as soon as it's up on the web site I'll let you know through this newsletter.
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--Chris Masterjohn, Editor
In This Issue
Cholesterol is the precursor to vitamin D, and dietary vitamin D is provided primarily by cholesterol-rich foods. This article describes this intimate connection between cholesterol and vitamin D, discusses the inferiority of the form of the vitamin found in irradiated plant and mushroom fats, discusses the almost entirely unstudied possibility that inhibiting cholesterol synthesis may lower vitamin D levels, and reports on the many new functions being discovered for this vitamin, as well as the findings that the current recommended intakes are far too low than needed for optimal health. For the chemically inquisitive, molecular structures are shown for vitamin D and related compounds.
Best of the 'Net
Low Brain Cholesterol Associated With Violent Suicide
Researchers have frequently observed a relationship between low blood cholesterol and suicide, with an even stronger relationship observed between low cholesterol and suicide committed by violent means or suicide committed by people with a history of violent behavior. Yet these studies have mostly been correlational, leaving the precise nature of this relationship to continue to elude scientists.
Researchers have hypothesized that low blood cholesterol reflects low brain cholesterol, but the relationship between blood cholesterol and brain cholesterol is poorly understood, and the relationship between brain cholesterol and suicide has until now not been studied.
A group of researchers published a study in the May, 2006 issue of the International Journal of Nueropsychopharmacology comparing the brain cholesterol levels of male suicide committers to those of age-matched victims of sudden death from causes not believed to be directly related to the brain.
Although there was no statistically significant difference in brain cholesterol content between suicide committers and controls, there was a large and highly significant difference in cholesterol content of specific areas of the frontal cortex related to suicidal behavior between the brains of those who committed suicide by violent means and those who committed suicide by non-violent means (as classified by Asberg et al., 1976). Lower cholesterol content of these areas was associated with violent suicide.
This study still leaves most of the questions about the relationship between low cholesterol, suicide and violent behavior unanswered, but it shows for the first time that in some -- but not all -- cases the consistent association found between low blood cholesterol and suicide does indeed reflect a lower cholesterol content in certain areas of the brain.
You can read my article on the importance of cholesterol to the brain here.
Policosanol Has No Effect on Cholesterol -- Is it a Cuban Scam?
A study published this month by German researchers in the Journal of the American Medical Association found that the popular alternative health supplement, policosanol, marketed as a cholesterol-lowering agent, had no effect on cholesterol levels in humans.
Many studies have shown that policosanol, a substance usually isolated from sugar cane wax that can also be obtained from wheat germ, rice bran, and beeswax, is as effective at lowering cholesterol in humans as are statin drugs. Yet nearly all of them have been conducted by Dalmer Laboratories, a Cuban firm established by the Center of Natural Products of the National Center for Scientific Research, La Habana Cuba, for the purpose of promoting policosanol.
One Russian study and one Argentinian study corroborated the Cuban research, while one study from the Netherlands found policosanol derived from wheat germ to have no effect on lipid levels. In contrast to many Cuban studies finding that policosanol lowers lipids in animals, a Canadian study found it to have no effect in hamsters.
The method by which policosanol supposedly lowers cholesterol is not known. Nevertheless, a recent meta-analysis found that a mean dose of just 12 mg per day of policosanol was associated with a mean reduction of 24%, including in trials that lasted less than 12 weeks. The meta-analysis included 30 studies, 29 from Cuba, and one from Argentina.
The researchers who published the JAMA study used policosanol produced in Cuba but tested it on German men and women aged 18 to 80, using five doses and a placebo for a duration of 12 weeks. Contrary to the many Cuban studies, the study found no satistically significant reduction in LDL, HDL, VLDL, total cholesterol, triglycerides, or lipoprotein (a).
In fact, only the mega-dose of 80 mg could achieve a statistically insignificant reduction in cholesterol levels that equalled that of the placebo, which was a pill that combined lactose and cellulose.
Why the difference? The study found that the diet of the subjects had no effect on the ability of policosanol to lower their lipid levels, and the duration of the study was similar to that of Cuban studies finding a large reduction in cholesterol. It's possible that the ethnic makeup of the populations were responsible for the differences, or something peculiar about the Cuban diet, but that wouldn't seem to explain why policosanol lowers the cholesterol of Cuban hamsters and not Canadian hamsters.
The fact that almost all of the published research on policosanol comes from a single Cuban firm that was established to market policosanol is... let's just say, suspicious.
But all of the policosanol studies miss the point. As reported in an earlier issue of the Cholesterol Times, a meta-analysis published last year found no relationship between a "lipid-lowering" agent's ability to reduce cholesterol and a lipid-lowering agent's ability to reduce heart disease mortality. Many methods that reduce cholesterol have no effect on mortality, and omega-3 fatty acids are more effective at lowering mortality than statins, even though they have no effect on cholesterol.
Additionally, high cholesterol levels, even LDL levels, have positive roles in preserving quality of life, especially in the elderly. Last year, for example, I reported on a study that found that high LDL levels protected against mobility limitation in the elderly.
When will researchers learn that cholesterol is not a disease, and that studies that look at a substance's ability to lower cholesterol, but do not look at that substance's ability to reduce mortality or increase the quality of life are completely useless?
Brain Cholesterol Levels Decline With Aging
A study published this month in Neuroscience Letters found that cholesterol synthesis in the hippocampus portion of the brain, but not the total amount of cholesterol, declines with aging.
The lipid content of the brain is over 12 times richer in cholesterol than that of the whole body. 70 percent of this cholesterol is associated with myelin, which forms the electrical insulation of nerve cells that allows proper transmission of electrical signals. Myelin function declines with age, which negatively impacts cognitive performance.
Lack of cholesterol supply in the hippocapus causes a failure of neurotransmission and the ability to form and break and reform connections between nerve cells as needed.
This study looked at the hippocampus portion of the brains of 20 autopsied humans, separated into two groups, one of ages 18 to 36, the other of ages 40 to 86.
The two groups did not differ in the total amount of cholesterol, but there was a significant difference in markers of cholesterol synthesis and an age-related decline in these markers, indicating that cholesterol is synthesized at a significantly higher rate in younger people than in older people.
The reason that the cholesterol level stayed the same appears to be that the brain compensated by lowering its degradation of cholesterol. Thus, the turnover of cholesterol is greatly reduced -- which could have negative effects on cognitive function -- probably fueled by the decrease in cholesterol synthesis.
Other studies have found a moderate decline in total brain cholesterol with aging.
Cholesterol is vital to the brain -- it is the limiting factor in synapse formation and quality (synapses are the connections between nerve cells) and its increased synthesis during sleep seems to be one of the reasons that sleep is good for our minds and brains. For more information on the role of cholesterol in the brain, see my article Learning, Your Memory, and Cholesterol.
Cholesterol Helps Facilitate Hydrogen Ion Flux Across the Cell Membrane
A recent study published in the Biochemical Journal by researchers Rebekah Gensure, Mark Zeidel, and Warren Hill has shown yet another role for cholesterol in the cell membrane: facilitating the flux of protons, or hydrogen ions (note that these two terms can be used interchangably), across the cell membrane.
This finding is particularly interesting because it seems to contradict the major theories about how protons travel across the cell membrane.
Cell membranes are somewhat permeable to water, but are virtually impermeable to charged ions because of the non-polar nature of the interior of the membrane. Yet for some reason, hydrogen ions, and possibly hydroxide ions, are capable of permeating the cell membrane somewhere between 100,000 and 1,000,000 times more easily than other similarly charged and structured ions.
There are three major theories about how protons travel through the cell membrane.
The first is that "water wires" are formed by single-file water molecules extending across the membrane, and that protons jump from one water molecule to the next, much like electrons jump from one atom to the next in a copper electrical wire.
The second is that there are random clusters of hydrogen-bonded water molecules that form, dissipate and reform within the cell membrane. When a proton attaches to one, it momentarily stabilizes the cluster, which lasts long enough to let the proton make its way through the cluster and jump to another until it finds itself on the opposite side of the membrane.
A third theory states that the conjugate bases of free fatty acids (a fatty acid missing a proton)or other weak bases in the membrane capture protons on one side of the membrane and easily slip through the inside of the membrane and deliver the proton to the other side.
Each of these theories predict that as membrane lipids become more compact, proton flux should decrease -- either because the compact lipids allow less room for and thus fewer water wires, because they allow less room for and thus fewer or smaller water clusters, or because they allow less room for and thus more constricted movement for free fatty acids and other weak bases that might transport protons.
Yet several observations seem to contradict this model. Cholesterol and a long-chain more-saturated-than-average phospholipid called sphingomyelin are found in large concentration in parts of the cell membrane called "lipid rafts" and in protective epithelial surfaces, where they function to grant the membrane greater compaction, either for protection, or to allow important proteins to stabilize and associate with one another. Yet a recent study showed that the high degree of compaction of the membranes of epithelial surfaces make them 18 times less permeable to water -- as we would expect -- but four times more permeable to hydrogen ions.
Gensure, Zeidel and Hill therefore set out to determine exactly what effect cholesterol and sphingomyelin have on the permeability of cell membranes to protons. They created artificial membranes that mimicked the composition of the lipid rafts of animal cells, made of phosphatidylcholine, sphingomyelin, and cholesterol, and varied the amount of sphingomyelin and cholesterol to see their effects.
As expected, cholesterol and sphingomyelin reduced the membrane's permeability to water by 70-90 percent. Yet, contrary to what we would expect from the major theories of proton flux, the same concentrations of cholesterol and sphingomyelin increased proton permeability about 4-fold to 5-fold.
Cholesterol had a more powerful effect than sphingomyelin.
The curious behavior of protons is quite different from water and other electrolytes, and isn't completely explained. Cholesterol and sphingomyelin caused the lipids to pack together in a dose-dependent manner -- the more cholesterol or sphingomyelin, the more they packed together. They also decreased water permeability in a dose-dependent manner. Likewise, the water permeability was associated with the lipid-packing in a dose-dependent manner.
Most other molecules to which the membrane is permeable are, like water, less able to diffuse through the membrane the more packed-together it becomes. But not protons.
Even more curious, the permeability of the membrane to all other molecules to which it is permeable is dependent on the concentration of the given molecule. The more there is on one side, the greater the degree to which it will flow through the membrane to the other side. With protons, not so.
No one knows quite why this is -- some have speculated that negative charges on the surface of the membrane can absorb protons and act as a sort of buffer against proton concentrations.
Likewise, no one yet knows why cholesterol fulfills its newfound function -- to facilitate increased proton flow, despite also facilitating the packing together of lipids in the membrane, which we'd expect to inhibit the flow of protons.
One possibility? The authors suggest that maybe it's not the quantity of water in the membrane, but the quality. Maybe the greater compaction causes the water wires -- or clusters -- in the membrane to become more ordered themselves, and thus facilitate proton transfer more easily.
After all, we can imagine that a mass of spread out frayed copper wire with no insulation would do us little good for running our electric tools and toys. We instead use thin and highly ordered wires wrapped tightly in a non-conductive wrapping so those electrons stay where they belong -- traveling straightly through the wire.
The study is just one more piece of evidence that cholesterol is in our bodies and in the bodies of every animal because it's supposed to be there.
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