General fitness, health and nutrition · Public discussion

Re The Cholesterol Paradox

Started by Nick · · Last activity · 5 posts · 1,071 views

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General fitness, health and nutrition
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4 December 2003
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  1. Seems like all of you are missing the point. The scientific evidence is overwhelming that only
    damaged/oxidized cholesterol is the problem. Remember that atherosclerosis occurs inside the cells -
    the commonly-held notion that "gunky" cholesterol gets "stuck" to artery walls is beyond ludicrous.
    It is basic biochemistry (free radical damage/disruption), that then goes into physiology (i.e., the
    inflammatory process), and it is clear that the authors of this study don't know this!!!! Thank
    goodness some scientists do, but the arrogance of those who don't is quite frightening. Here's just
    one well-written example of the evidence:

    Reducing Free Radicals - A Dietary Revolution By Dr Steven Gieseg Published in New Zealand Science
    Monthy, (1999) July, 6-8. Over the past few years, free radicals have been implicated in many
    different diseases. Every health supplement seems to include some protection against them - but what
    are they and more importantly, what do they do? A free radical is a chemical with a very reactive
    chemical bond. The chemical bonds which hold atoms together to make molecules contain pairs of
    electrons. For example there are two electrons in each of the bonds holding the hydrogens to the
    oxygen in the water molecule. The two electrons stabilise the bond between the atoms. However, some
    molecules, especially those containing oxygen, can easily gain only one of a pair of these bonding
    electrons. In a sense we have a molecule with a free chemical bond. Essentially a free radical is a
    molecule containing unpaired electrons. An unpaired electron makes the molecule very reactive. The
    molecule will "steal" an electron from other molecules in order to gain a pair for its' lone
    electron. The structure of the molecule that loses the electron is subsequently changed and can
    often become a free radical itself. The most reactive free radical molecule known is the hydroxyl
    radical. It can be made by X-rays or gamma rays splitting water molecules. The hydroxyl radical,
    written HO· to show the lone electron, is so reactive that it only takes one billionth of a second
    to react with a neighbouring molecules, usually by stealing hydrogen atoms from other molecules. The
    hydroxyl radical regains the lost electron in this manner and forms a water molecule
    (H2O). To regain its' electron pair, the hydroxyl radical has changed another molecule by removing a
    hydrogen electron from it. This causes further reactions leading to a major chemical change in
    the molecule. If the molecule the hydroxyl radical steals the hydrogen from is a piece of DNA,
    a genetic mutation may occur resulting in a cancer gene being switched on. Superoxide
    Thankfully exposure to gamma rays is not an everyday event for most of us. Superoxide rather
    than the hydroxyl radical is the most commonly encountered free radical in biology. Superoxide
    is an oxygen molecule with an extra unpaired electron and is usually written as O2.-.
    Superoxide is formed in the body either deliberately by white blood cells to kill invading
    bacteria and viruses, or as a leakage of energy when cells burn food molecules. In both
    situations it appears the superoxide formed can cause changes to the biological molecules of
    our bodies, which results in various types of damage. Some of this damage can appear as
    clinical diseases. Superoxide from White Blood Cells A major source of superoxide is the
    specialised white blood cells called macrophages and neutrophils. An enzyme, (NADPH oxidase) is
    found on the surfaces of these cells. This enzyme is activated when the macrophages and
    neutrophils encounter a foreign invading molecule like a bacteria. The enzyme adds an electron
    to the oxygen molecules around it creating superoxide. Superoxide is not very reactive even
    though it is a radical. It usually reacts with itself to form hydrogen peroxide. Hydrogen
    peroxide is often referred to as a reactive oxygen species (ROS) and is toxic to many bacteria.
    It destroys the bacteria by oxidising various metabolic control molecules (possibly thiol
    groups) and generates further radicals within the bacteria by reacting with copper and iron.
    The neutrophils can enhance the destructive power of hydrogen peroxide by reacting it with the
    salt in our body using an enzyme called myeloperoxidase. This enzyme is an amazing green colour
    in the test tube but most people are familiar with it as the green phlegm in their handkerchief
    during a bad head cold. This enzyme converts the hydrogen peroxide to hypochlorite, also known
    as chlorine bleach. Chlorine bleach is a potent and lethal killer of bacteria. Unfortunately it
    also kills anything else it encounters such as your healthy cells. When unleashed on a cell it
    destroys the enzymes and protein structures by adding chlorine atoms to them. This causes cell
    metabolism to grind to a halt and the cell dies. Hypochlorite production, at the wrong time,
    wrong place or in excess has been implicated in a number of diseases including those of the
    lungs and possibly the heart. Superoxide as an energy leakage. We like to think of our body as
    a perfect machine but it is not. Five percent of the oxygen we breathe ends up as superoxide.
    The final stage of generating energy from the foods we eat involves a series of reactions where
    electrons are passed from one molecule to the next, forming a type of electric current. This
    process is known as the respiratory chain and occurs in the cells mitochondria. One time out of
    twenty, one of the electron carriers, called Coenzyme Q, passes the electron to oxygen instead
    of the next electron carrier, so producing superoxide. The superoxide generated within the cell
    will react with a number of important molecules if not removed quickly. The most significant of
    these vulnerable molecules is nitric oxide, one of the central blood pressure controlling
    molecules in the body. To prevent this superoxide mediated damage, all cells contain the enzyme
    superoxide dismutase. This enzyme speeds up the reaction between superoxide molecules that
    forms hydrogen peroxide. Ironically, hydrogen peroxide is, as mentioned earlier, toxic to cells
    and must also be removed. The majority of the hydrogen peroxide is broken down to oxygen and
    water by the cellular enzyme catalase. In addition to catalase, the body also has a group of
    selenium-containing enzymes collectively called glutathione peroxidases. These enzymes break
    down hydrogen peroxide and any peroxides which form on fats and oils within the body. They are
    called glutathione peroxidases because they transfer the energy of the reactive peroxides to a
    very small sulphur containing protein called glutathione. The selenium contained in the enzymes
    acts as the reactive centre, carrying reactive electrons from the peroxide to the glutathione.
    It is the glutathione that is the antioxidant in the reaction, not the selenium as many health
    food companys would lead us to believe. Selenium by itself is a potent oxidant which can be
    very toxic if to much is taken. Antioxidants The body creates free radicals and oxygen reactive
    species relentlessly and continuously. Antioxidants are compounds which provide our body with
    protection against the harmful effects of damaging free radicals and other reactive oxygen
    species. By definition an antioxidant is a compound that is able to react with free radicals,
    forming harmless unreactive molecules and protecting other biological molecules from damage.
    Antioxidants are either reactive chemicals such as vitamin E or specialised enzymes such as
    catalase. The body produces enzymatic antioxidants but it cannot make antioxidant chemicals
    such as vitamin E, C and flavanoids. These antioxidant chemicals protect the sites in the body
    which the enzymatic systems cannot reach. We obtain these antioxidant chemicals from our diet
    but they are rapidly turned over in the body and need to be constantly replenished. Vitamin E
    is an antioxidant which dissolves in our body's fats and oils. Any radicals formed in the fats
    will react with vitamin E to form a vitamin E radical. This vitamin E radical lacks the energy
    to cause any further damage but will react with vitamin C in the blood to regenerating the
    vitamin E. The breakdown product of vitamin C is then removed by the kidneys. In this way
    radicals formed in fats are removed from the body by transfer to vitamin E then to vitamin C
    and out through the kidneys as urine. Vitamin C also reacts with a number of water soluble
    radicals formed in the blood. Flavanoids are another antioxidant which may be of great
    importance to our health. Flavanoids are ring shaped compounds found in most plant tissues and
    usually have a reddish colour. They are compounds that give red wine its' colour and possibly
    its' beneficial health effects. It has been suggested by many scientists that one of the
    beneficial effects of eating fresh fruit and vegetables may be the intake of the flavanoid
    antioxidants. Commercial interest in these compounds as dietary supplements has made them the
    focus of a considerable amount of research both here and overseas. Free radicals: the friction
    wearing out the metabolic machine It appears that for at least the first twenty to thirty years
    of our lives our bodies are well protected from free radical damage. Assuming one has a healthy
    diet containing fresh fruit and vegetables, the levels of antioxidant molecules and antioxidant
    enzymes is usually high enough to absorb most of the free radicals produced in the body. As we
    get older the effectiveness of these protective systems appears to slowly decrease. It seems
    not all the free radicals produced are neutralised so there is a slow build up of damaged
    molecules. The enzymatic antioxidant defence systems also appear to be vulnerable to free
    radical damage. As we age there is a slow decrease in the amount of active radical removing
    enzymes in our bodies. As friction wears out a machine, free radicals wear out the body. This
    is why severe complications of free radical damage appear as the diseases we associate with
    aging. The table shows a few of the diseases that free radicals are thought to contribute to.
    Free Radical and Antioxidant Research It is believed by many scientists and medical
    practitioners that increasing the dietary intake of antioxidants, either by increased
    consumption of fresh fruit and vegetables, or dietary supplements of vitamin E, C and possibly
    flavanoids, the processes of free radical damage and the associated diseases can be slowed.
    Proving this is a very slow and difficult process because free radicals are very reactive and
    therefore very short lived. Scientists cannot measure these radicals directly but must look for
    the damage they cause as an indication they are present. Unfortunately, free radical reactions
    are at best described as being messy. The hydroxyl radical can form over a hundred different
    products when it reacts with a protein. The situation is even more complex with fats. Many of
    the products of free radical damage to fats are unstable and break down into even more complex
    compounds. The measurement of one of these compounds in the blood does not always mean that
    body is being damaged permanently as the body may be dealing with the damage successfully by
    removing it. To make the task more complex, diseases such as heart disease develop very slowly,
    over many years, at rates impractical to model in the test tube. To overcome these problems
    scientists continue to develop model systems which show how the biological chemistry reacts to
    free radicals. New markers of free radical damage are also being developed to monitor what
    actually happens within the body. The goal of this research is to produce a non-invasive way of
    measuring the level of free radical damage in various diseases and to deliver the appropriate
    amount of antioxidant therapy. Table Selected age related diseases possibly caused by free
    radical damage Coronary Heart Disease. Coronary Heart disease (atherosclerosis) appears to be
    caused by damage to the cholesterol carrying particles in the blood called low density
    lipoprotein. Free radicals may be the source of the damage. The damaged particles are taken up
    by white blood cells called macrophages, which collect in the artery wall forming plaques. The
    cholesterol filled cells attract other cells causing a growth on the inside of the artery which
    slows or blocks the flow of blood to the heart. If the growth breaks open the blood will clot
    possibly blocking the flow of blood to the heart muscle resulting in a heart attack.. Stroke
    Same as Heart disease but arteries supplying the brain with blood are affected.

    Cancer Free radicals can react with the cell's DNA causing mutations. If the free radical damage is
    not repaired, the DNA sequence will change. This may result in the switching on of cancer causing
    growth genes or the switching off of cancer stopping genes within the cell. Usually a cell requires
    two or more genes to be altered before it becomes cancerous. The majority of cancers and other
    genetic mutations are caused in this way.

    Arthritis Active white blood cells damage the cartilage of the joint causing pain and swelling. Some
    of this damage may be due to the release of free radicals.

    Alzheimers Damaged proteins build up in specific areas of the brain and the various neurons begin to
    die. May have a free radical mechanism.

    Cataracts The formation of cataracts involves the oxidation of the lens proteins. UV light and
    possibly iron generate free radicals which cause sugar molecules and other compounds to react with
    the lens proteins forming colour compounds which block the passage of light through the lens.

  2. nick said:


    Seems like all of you are missing the point. The scientific evidence is overwhelming that only
    damaged/oxidized cholesterol is the problem. Remember that atherosclerosis occurs inside the cells
    - the commonly-held notion that "gunky" cholesterol gets "stuck" to artery walls is beyond
    ludicrous.

    While it's certainly true that cholesterol doesn't clog up the arteries like limescale clogs up
    water pipes, atherosclerosis *doesn't* occur in cells. The initial oxidised fatty deposits that
    start the process off occur in the extracellular spaces in the artery wall, between the
    endothelial and smooth muscle cells. White blood cells invade the artery wall to attack the fatty
    deposits and end up making it worse. A combination of increasing deposit of oxidised fat and
    smooth muscle cell proliferation follows, which causes a bulge in the artery wall that reduces the
    diameter of the artery.

    MattLB

  3. nick said:

    Thankfully exposure to gamma rays is not an everyday event for most of us.

    Huh. The person never has read what background radiation from sky is consisting of :-) But, compared
    to the superoxide production in body, it is of minor importance, but everybody is exposed to gamma
    irradion, more or less constantly and is the basis of evolution.

    Quoted message said:

    The neutrophils can enhance the destructive power of hydrogen peroxide by reacting it with the
    salt in our body using an enzyme called myeloperoxidase. This enzyme is an amazing green colour in
    the test tube but most people are familiar with it as the green phlegm in their handkerchief
    during a bad head cold. This enzyme converts the hydrogen peroxide to hypochlorite, also known as
    chlorine bleach. Chlorine bleach is a potent and lethal killer of bacteria. Unfortunately it also
    kills anything else it encounters such as your healthy cells. When unleashed on a cell it destroys
    the enzymes and protein structures by adding chlorine atoms to them. This causes cell metabolism
    to grind to a halt and the cell dies. Hypochlorite production, at the wrong time, wrong place or
    in excess has been implicated in a number of diseases including those of the lungs and possibly
    the heart.

    Here is where a proper taurine status comes in. Taurine in cells is the defendent number one in its
    high reactivity with HOCl-. And taurine chloramine is an important signal molecule in many respects,
    also as an immune system modulator. While other amino acids only form degenerative substances with
    hypochlorite, like homocysteine. Maybe why hyperhomocysteniamia may be deletirious. Outside cells,
    taurine normally is at low concentration, but in attacked or damaged cells it leaks out and that may
    prevent neighbouring cells from being attacked. Otherwise polyamines may be preventive??

    It has been shown in people with too high myeloperoxidase activity that they find
    dichloroaminetaurine, that is, taurine has reacted twice with hypochlorite. That is a deleterious
    molecule, opposite of monochloramine taurine. Taurine supplementation has been tried in such cases,
    but most possibly with far too little taurine supplementation (500 mg daily is the only I have seen
    in papers).

    Quoted message said:

    Superoxide as an energy leakage. We like to think of our body as a perfect machine but it is not.
    Five percent of the oxygen we breathe ends up as superoxide. The final stage of generating energy
    from the foods we eat involves a series of reactions where electrons are passed from one molecule
    to the next, forming a type of electric current. This process is known as the respiratory chain and
    occurs in the cells mitochondria. One time out of twenty, one of the electron carriers, called
    Coenzyme Q, passes the electron to oxygen instead of the next electron carrier, so producing
    superoxide.

    If the food you contains ethoxyquine, ethoxyquine will compete with ubiquinone (coenzyme Q) and
    transfer all electrons to oxygen in order to produce free radicals. Ethoxyquin is often found in cat
    and dog commercial food, and also in all kind of food where the animal is fed ethoxyquin containing
    food, like commercial fish powder produced for animal feeding. Like chicken, cattle, farmfed fish
    like salmon and trout etc. Never try to eat fish powder contaminated with ethoxyquin which is added
    in order to prevent fire or explosions in bulk transport of fish powder for animal use. That is in
    order to save money instead of using inert atmosphere in ships under transport (which is more
    expensive that adding ethoxyquin. Ethoxyquin addition should be banned worldwide due to its effect
    on mithochondria, and it is a highly fat soluble molecule with almost complete retaining in body,
    almost no transport out of body since it cannot be made water soluble by reactions with taurine etc.

    Quoted message said:

    The superoxide generated within the cell will react with a number of important molecules if not
    removed quickly. The most significant of these vulnerable molecules is nitric oxide, one of the
    central blood pressure controlling molecules in the body. To prevent this superoxide mediated
    damage, all cells contain the enzyme superoxide dismutase. This enzyme speeds up the reaction
    between superoxide molecules that forms hydrogen peroxide. Ironically, hydrogen peroxide is, as
    mentioned earlier, toxic to cells and must also be removed.

    In order to have a functional superoxide dismutase, your body need copper and manganese. In western
    society, copper intake is marginal due to purification of food by refining. And partly by binding it
    with anions which make it insoluble in water and thus not available to body.

    Quoted message said:

    Cataracts The formation of cataracts involves the oxidation of the lens proteins. UV light and
    possibly iron generate free radicals which cause sugar molecules and other compounds to react with
    the lens proteins forming colour compounds which block the passage of light through the lens.

    Here aldose reductase which converts sugar molecules to it's respective sugar alcohols are
    important. There are many ways to induce aldose reductase production which is controlled by the
    signal pathway involving NF-kappaB. Free radicals and oxidative stress are such one. But also cell
    volume changes due to variations of osmotic pressure, from either sodium variations or sugar
    molecule concentration variances are important. And here again taurine status plays a role by being
    the main regulator of cell volume by cell release of taurine at hypoosmotic pressure which expands
    cell volume and by uptake during hyperosmotic pressure like when sodium or glucose concentration
    increase and cell volume decreases. If taurine is lacking, other systems are activated and oxydative
    stress increases, NF-kappaB is induced and in turn aldose reductase is induced to turn glucose into
    sorbitol which may react with proteins and galactitol from galactose which are far more reactive. If
    aldehyde variants are formed from these molecules (glucose, galactose either in noncyckic form or
    from degradation products during glycolysis like glyceraldehyde and perhaps degradation products
    from sorbitol may form aldehydes) these may either react with proteins, taurine, GSH and other
    thiolgroup or free amine groups, If these preventive molecules are more or less devoid because bad
    nutritious status from eating highly refined food, cataract induction may be increased.

    Not only UV radiation and iron free radical formation is of importance, glucose degradation is in
    itself a big free radical producer, eg. NADH -> NAD+ + free radical instead of H+ during some
    catalyzed systems and many other pathways.

  4. MattLB said:

    While it's certainly true that cholesterol doesn't clog up the arteries like limescale clogs up
    water pipes, atherosclerosis *doesn't* occur in cells. The initial oxidised fatty deposits that
    start the process off occur in the extracellular spaces in the artery wall, between the endothelial
    and smooth muscle cells. White blood cells invade the artery

    Have you though on how cholesterol get there, inside the endothelial cell layer??

    Check with transcytosis, earlier denominated something different so there is still few articles
    using that term. But in fact, cholesterol are taken up by cells and transported through the cell and
    release in the intima btw. endothelial layer and smooth muscle cells.

    The transport is regulated by PKC, and the key inducers are high glucose concentration and some
    lesser degree arachidonic acid, linoleic acid, some saturated fats, while most saturated fats are
    inidifferent in stimulating. But stearic acid is a weak inhibitor together with another one.
    Alphalinolenic acid is a strong inhibitor, so here is an important role for omega-3 acids since
    almost all omega-3 acids are more or less inhibitors of PKC stimulation of transcytosis.

  5. Alf Christophersen said:


    MattLB said:

    While it's certainly true that cholesterol doesn't clog up the arteries like limescale clogs up
    water pipes, atherosclerosis *doesn't* occur in cells. The initial oxidised fatty deposits that
    start the process off occur in the extracellular spaces in the artery wall, between the
    endothelial and smooth muscle cells. White blood cells invade the artery

    Have you though on how cholesterol get there, inside the endothelial cell layer??

    Check with transcytosis, earlier denominated something different so there is still few articles
    using that term. But in fact, cholesterol are taken up by cells and transported through the cell
    and release in the intima btw. endothelial layer and smooth muscle cells.

    Unoxidised LDL passes to and fro across the endothelium without problem, but oxidised forms bind to
    the extracellular matrix far more strongly and are retained in the sub-endothelial space, where they
    become targets for macrophages. You need macrophagic involvement and the inflammation that goes with
    it to form a plaque. The presence of endothelial damage
    e.g. due to high blood pressure at arterial branch points, increases the flow of LDL into the artery
    wall, but you still need oxidation of the LDL for net retention in the wall.

    MattLB

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