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Cholesterol Metabolism and Treatments of Hypercholesterolemia

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Regulation of Cholesterol

The cellular supply of cholesterol is maintained at a balanced level by three distinct mechanisms:

1)Regulation of HMGR, HMG-reductase activity and levels. HMG is the product of condensation of two molecules of Aceto-acetyl-coA in the biosynthesis of cholesterol.

2)Regulation of excess intracellular free cholesterol through the activity of sterol O-acyltransferases, SOAT1 and SOAT2 which is the predominant activity in liver.

3)Regulation of plasma cholesterol levels via LDL receptor-mediated uptake and HDL-mediated reverse transport.

The first three control mechanisms are exerted by cholesterol itself. Cholesterol acts as a feed-back inhibitor of pre-existing HMGR as well as inducing rapid degradation of the enzyme. In addition, when cholesterol is in excess the amount of mRNA for HMGR is reduced because of decreased expression of the gene.

-The feedback mechanisms are typical of metabolic pathways, same happens with thyroid hormones, T3 and T4, they act as inhibitors of their own production when levels are too high controlling the release of TSH whose demand decreases in this case and its level goes down; in the opposite way when levels of the hormones are low, there is more demand of production and TSH level goes up.

The thyroid metabolism also influences the cholesterol level, especially while in hypothyroidism, in this case with low levels of thyroid hormones all the metabolic functions are reduced and delayed and therefore there is not metabolization of cholesterol and more accumulation-

Regulation of HMGR through covalent modification occurs because of phosphorylation and dephosphorylation. The enzyme is most active in its unmodified form. Phosphorylation of the enzyme decreases its activity. HMGR is phosphorylated by AMP-activated protein-kinase, AMPK. AMPK itself is activated via phosphorylation. Phosphorylation of AMPK is catalyzed by at least two enzymes.

The activity of HMGR is additionally controlled by the cAMP signaling pathway. Increases in cAMP lead to activation of cAMP-dependent protein kinase, PKA. When the regulatory subunits are phosphorylated by PKA the activity of the associated phosphatases is reduced which results in AMPK remaining in the phosphorylated and active state, and HMGR in the phosphorylated and inactive state.

As the stimulus leading to increased cAMP production is removed, the level of phosphorylation decreases and that of dephosphorylations increases. The net result is a return to a higher level of HMGR activity. In contrast, insulin leads to a decrease in cAMP, which in turn activates cholesterol synthesis.

The ability of insulin to stimulate, and glucagon to inhibit HMGR activity is consistent with the effects of these hormones on other metabolic pathways. The basic function of these two hormones is to control the availability and delivery of energy to all cells of the body.

Long-term control of HMGR activity is exerted primarily through control over the synthesis and degradation of the enzyme. When levels of cholesterol are high, the level of expression of the HMGR gene is reduced. Conversely, reduced levels of cholesterol activate expression of the gene. Insulin also brings about long-term regulation of cholesterol metabolism by increasing the level of HMGR synthesis.

Treatment of Hypercholesterolemia

Reductions in circulating cholesterol levels can have profound positive impacts on cardiovascular disease, particularly on atherosclerosis.

Yet, the statement tests that: “Control of dietary intake is one of the easiest and least cost way to achieve reductions in cholesterol”.

-This assertion, and which is the obvious one contrasts the one stating that “More cholesterol we introduce with diet, less is produced by liver”. But, reasoning they seem both to make sense if we consider the feedback mechanism-

Recent studies in laboratory rats have demonstrated an additional benefit of reductions in dietary cholesterol intake. In these animals it was observed that reductions in dietary cholesterol not only resulted in decreased serum VLDL and LDL, and increased HDL but DNA synthesis was also shown to be increased in the thymus and spleen. Based on histological examination of the spleen, thymus, and lymph nodes it was found that there was an increased number of immature cells and enhanced mitotic activity indicative of enhanced proliferation. These results suggest that a marked reduction in serum LDL, induced by reduced cholesterol intake, stimulates enhanced DNA synthesis and cell proliferation.

Drug treatment to lower plasma lipoproteins and/or cholesterol is primarily pointed at reducing the risk of atherosclerosis and subsequent coronary artery disease that occurs in patients with elevated circulating lipids. Drug therapy usually is considered as an option only if non-pharmacologic interventions like altered diet and exercise have failed to lower plasma lipids.

Statins, the most common therapy, are drugs that inhibits HMG-CoA reductase, HMGR. The net result of treatment is an increased cellular uptake of LDL, since the intracellular synthesis of cholesterol is inhibited, and cells are therefore dependent on extracellular sources of cholesterol. However, since mevalonate, the product of the HMG-CoA reductase reaction, is required for the synthesis of other important isoprenoid compounds besides cholesterol, long-term treatments bring some risk of toxicity.

It seems that the statins have become recognized as a class of drugs capable of more pharmacologic benefits than just lowering blood cholesterol levels via their actions on HMGR. Part of the cardiac benefit of the statins relates to their ability to regulate the production of anti-inflammatory compounds.

Statins seems to also have some effects on immune function, like attenuation of autoimmune disease, inhibition of T-cell proliferation, inhibition of inflammatory co-stimulatory molecule expression, decreases in leukocyte infiltration, and promotion of a shift in cytokine profiles of helper T-cell types from Th1 to Th2.

Another common drug used now for lowering cholesterol is Nicotinic acid, or Niacin, or vitamin B3. This reduces the plasma levels of both VLDL and LDL by inhibiting hepatic VLDL secretion. In addition, nicotinic acid administration strongly increases the circulating levels of HDL. Unfortunately, is administration is compromised for the unpleasant side-effect of flushing, as strong cutaneous vasodilation.

-These the most common drugs of conventional therapy, but there are more than these-

Alternative Options of Treatments

The natural options for lowering cholesterol are various, I will just mention the most typical elements present in the major number of supplements, and most typical suggestions and tips that can be found online as soon as we look for “natural option, or natural remedies for lowering cholesterol”.

As we all know, diet and exercise are number one priority and essential steps to take for most of the diseases, and fibers, especially soluble fibers, are the most recommended, oat, barley and psyllium are the best, but oat-B-glucans are a specific type of oat that seems to lower the bad cholesterol at particularly good percentage of rate.

Here some of the most typical suggested foods to lower cholesterol.

By Pinterest.com

Niacin, fish oil, CoQ10, garlic, plant sterols and stanols, red yeast rice (the natural version of statins), pantetheine or vitamin B5 analog, olive leaves, bergamot, berberine, choline and phosphatidylcholine, and many more compounds or herbs can be found in different arrangements and assembling in supplements for cholesterol; it depends on the company, some they have more elements, some usually two or three of these mentioned.

What it looks important about mono and polyunsaturated fats, and which are respectively oil of olive and omega’s-3 is that they reduce the oxidation of lipoprotein, the dangerous step toward plaque formation and clogging of arteries, decrease of LDL, and increasing of HDL.

One of the most recommended products online besides the most typical is “Cholesteoff”, made by Nature Made and containing Sterols and Stanols, plus Pantetheine, I believe. I am mentioning because I found some interesting information in regard of soy and so of sterols and seems that they really have been taking always more in consideration.  

In this paragraph from a book of Natural Medicine has been examined the influences of soy on cholesterol metabolism; it seems that regular intake of soy foods, especially in place of more common animal protein sources, leads to modest meaningful cholesterol reductions in hypercholesterolemic individuals. Soy’s main mechanisms of action for this appear to be interfering with cholesterol absorption, increasing fecal bile acids excretion, and upregulating low density lipoprotein (LDL) receptor expression.

Individual studies found that hyperlipidemic men and women receiving soy protein with isoflavones in addition to a National Cholesterol Education Program showed significantly lower total cholesterol, estimated coronary artery disease risk, total/high-density lipoprotein (HDL) ratio, LDL/HDL ratio, and apolipoprotein B/A-1 ratio than those using the program and diet alone; LDL cholesterol, apolipoprotein B,, homocysteine, and oxidized LDL levels were also lower with soy than during the program and diet alone.

In a similar study hypercholesterolemic postmenopausal women receiving soy protein and isoflavones in addition to program and diets showed a greater decrease in non-HDL cholesterol than those receiving program and diets alone, and those receiving soy protein and isoflavones also showed increases in HDL cholesterol, as well as decrease in LDL levels.

The results of a 2010 study suggest that soy foods’ potential benefits to lipid profiles may be significantly improved by combination with a prebiotic like inulin. Hyperlipidemic men and women given 30 g soy protein, 61 mg soy isoflavones, and 10 g oligofructose-enriched inulin showed significant improvements in measures of LDL and HDL cholesterol compared with either soy or prebiotic alone.

As for the most today the solutions are different within the same conventional medicine and with the integrative even more; it is always up to us the final decision and what we feel are body can tolerate or not, interferences with other medications or supplements that we already take and capability of the systems to process everything, mainly gastroenteric and urinary system and even more the liver where everything is processed.

Thanks For Reading.

Mariarosaria M.

Sources:

Themedicalbiochemistrypage.org

Textbook of Natural Medicine, 2020, Cheryl Kos ND, by sciencedirect.com

Introductory picture by Healthline.com

Cholesterol, Metabolic Pathways and Correlations

Cholesterol is one of the subjects I am personally interested because despite of my lifestyle and the way I eat, it keeps on average normally high, especially the LDL compound.

As much as I am acknowledged and understand as biologist, I have learned from books and articles, talked about in previous blogs, and aware of the benefits and function, I am honestly, at this time concerned about, especially in regard of the LDL compound, and this is why I have been researching more and looked at a molecular and biochemical level trying to understand where this cholesterol comes from, and/or which pathways are involved and connected, as much as  always more persuaded of the genetic origins and overproduction by liver.

I still cannot get the complete picture of what does happen inside the incredible microscopic environment of our body and our cells and systems, so interconnected and complex, especially when we start to look at the metabolic pathways.

The questions remain for me a little bit, and this is the reason why I am brainstorming and assembling fractions of these biochemical steps and descriptions partially rearranged to simplify the original content and clarified.

Cholesterol is a sterol, present in animal tissue, in large concentration in liver and brain. It is the structural component of all cell membranes, regulates fluidity and confers stability, and has an important role in brain synapsis and the immune system.

It is also the precursors of bile acids, steroid hormones, and vitamin D.

Hydrophobic compound made of four fused hydrocarbon rings, A, B, C and D called steroid nucleus, and with 8 carbon branched hydrocarbon chain (CH) attached to C17 of D-ring. Ring-A has a hydroxyl group (OH) at C3, ring-B a double bond between C5 and C6.

Cholesterol is an extremely important biological molecule that has roles in membrane structure as well as a precursor for the synthesis of the steroid hormones, bile acids, and vitamin D. Both dietary cholesterol, and that synthesized “de novo”, are transported through the circulation in lipoprotein particles. The same is true of cholesteryl esters, the form in which cholesterol is stored in cells. Due to its important role in membrane function, all cells express the enzymes of cholesterol biosynthesis.

The synthesis and utilization of cholesterol must be tightly regulated to prevent over-accumulation and abnormal deposition within the body. Of clinical importance is the abnormal deposition of cholesterol and cholesterol-rich lipoprotein in the coronary arteries, leading cause of atherosclerosis, and coronary arteries diseases.

Cholesterol Biosynthesis

Cholesterol is synthesized by all tissues in human, an essential molecule in many animals, including human but is not required in diet as all cells can synthesize it from simple precursors. It is made of 27 carbon compounds. All the carbon atoms in the cholesterol are provided by acetate. NADPH provides the reducing equivalents.

The biosynthesis pathway of cholesterol is endergonic and so requires ATP. To produce 1 mole of cholesterol are necessary 18 moles of Acetyl coA, 36 moles of ATP and 16 moles of NADPH.

In the first step in cholesterol biosynthesis, step I, two molecules of acetylcoA condenses to form AcetoacetylcoA. The reaction is catalyzed by enzyme thiolase.

AcetoacetylcoA condenses with another molecule of acetylcoA to form β-hydroxyl-β-methyl-glutaryl-coA (HMG).

-An elementary observation, acetyl-coA is a molecule of the Krebs cycle, the major step of the general metabolism where glucose in presence of oxygen is metabolized and decomposed in water and carbon dioxide through a number of reactions catalyzed by different enzymes and with ox-reduction processes that allow flow of electrons and release of energy. The cholesterol biosynthesis therefore steels substrates for the Krebs cycle, generating increase demand for glucose and so of carbohydrates and that is why also the carbs relate to the cholesterol production-

In step II, reduction of HMG-coA to Mevalonate is catalyzed by HMG-coA reductase enzyme and happens in in cytosol, in this reaction 2 NADPH are used for donation of 2 electrons. This reaction is the key step in regulation of cholesterol biosynthesis.

In step III, three phosphate groups are transferred from three ATP molecules to Mevalonate to generate Isoprene units.

During step IV, six activated units of isoprene condense with elimination of both pyrophosphate group to form Squalene.

In step V Squalene is converted in Lanosterol, which contains four rings steroid nucleus, through hydroxylation and cyclization utilizing NADHP.

Finally in Step VI happens the conversion of Lanosterol into Cholesterol where Lanosterol undergoes a series of about 20 reactions to finally convert into cholesterol.

Cholesterol Synthesis Pathway - YouTube

-These are instead some and more common molecules involved in the pathways, the steps are endless and too complex to report each of them, I have tried to summarize in a way –

Cytochrome P450 enzymes are involved in a diverse array of biological processes that includes lipid, cholesterol, and steroid metabolism. The common nomenclature for P450 enzymes is CYP. There are at least 57 CYP enzymes in human tissues, eight of these are involved in cholesterol biosynthesis and metabolism, which includes conversion of cholesterol to bile acids. CYP metabolism of cholesterol generates several oxysterols that function as biologically active molecules such as in the activation of liver receptors.

Coenzyme Q, or ubiquinone is a red-ox active molecule that is composed of a benzoquinone ring conjugated to a polyisoprenoid tail that is of variable length in different species and organisms. In humans the polyisoprenoid tail consists of 10 isoprenoid units which impart the common name for the molecule as CoQ10. In undergoing reduction and oxidation reactions the electrons are accepted and donated from benzoquinone ring. The polyisoprenoid tail of ubiquinone serves to anchor the molecule in the membrane.

-Here is why the importance of taking CoQ10 during therapy with Statins, as we can see CoQ10 is an important molecule in the cholesterol metabolism-

Heme A is an essential component of the oxidative phosphorylation pathway by serving as the prosthetic group for cytochrome c oxidase of complex IV. Cytochrome c is so-called due to the presence of two distinct heme a prosthetic group with heme a being the direct electron donor in the complex IV catalyzed reduction of O2 to H2O.

Regulation of Cholesterol

A relatively constant level of cholesterol in the blood (150–200 mg/dL) is maintained primarily by controlling the level of de novo synthesis. The level of cholesterol synthesis is regulated in part by the dietary intake of cholesterol.

-In regard of this assertion I just want to mention some that I read from a nutrition book, and that made me wonder, the book was stating that “more fat we eat, less cholesterol is produced from the body” Is this the reason why they were emphasizing the importance of eating fats and of ketogenic diet? To me sounds still controversial-

Cholesterol from both diet and synthesis is utilized in the formation of membranes and in the synthesis of the steroid hormones and bile acids. The greatest proportion of cholesterol is used in bile acid synthesis.

The cellular supply of cholesterol is maintained at a steady level by three distinct mechanisms:

  1. Regulation of HMGR activity and levels.
  2. Regulation of excess intracellular free cholesterol through the activity of sterol O-acyltransferases, SOAT1 and SOAT2 which is the predominant activity in liver.
  3. Regulation of plasma cholesterol levels via LDL receptor-mediated uptake and HDL-mediated reverse transport.

Regulation of HMGR activity is the primary means for controlling the level of cholesterol biosynthesis. The enzyme is controlled by four distinct mechanisms: feed-back inhibition, control of gene expression, rate of enzyme degradation and phosphorylation-dephosphorylation.

The Utilization of Cholesterol

Cholesterol is transported in the plasma predominantly as cholesteryl ester associated with lipoproteins. Dietary cholesterol is transported from the small intestine to the liver within chylomicrons. Cholesterol synthesized by the liver, as well as any dietary cholesterol in the liver that exceeds hepatic needs, is transported in the serum within LDL. The liver synthesizes VLDL, and these are converted to LDL through the action of endothelial cell-associated lipoprotein lipase. Cholesterol found in plasma membranes can be extracted by HDL and esterified by the HDL-associated enzyme lecithin-cholesterol acyltransferase, LCAT. The cholesterol acquired from peripheral tissues by HDL can then be transferred to VLDL and LDL via the action of cholesteryl ester transfer protein (CETP) which is associated with HDL.

Reverse cholesterol transport allows peripheral cholesterol to be returned to the liver in LDL. Ultimately, cholesterol is excreted in the bile as free cholesterol or as bile salts following conversion to bile acids in the liver.

-To make simple the role of HDL is to absorb cholesterol from the body and to carry to the liver from where then will be flushed out from the excretory systems, while LDL delivers fat molecules to the cells and is involved in atherosclerosis, a process where LDL is oxidized within the arterial walls and responsible of plaques production and so of blood flow blockage and cardiovascular consequences-

As we can see the steps and regulation are endless, and utilization differs based on the lipoproteins of transport and site of production, for this reason the subject must be separated in more steps.

To be continued

Thanks For Reading

Mariarosaria M.

Sources:

Pubchem.ncbi.nih.gov/pathway/wikipathways

themedicalbiochemistrypage.org

Onlinebiologynotes.com

Picture by youtube.com

Coagulation and Blood Consistency

Définition | Coagulation | Futura Santé

Blood at glance

Blood is a fluid that delivers necessary nutrients and oxygen to the body’s cells and from which retains metabolic waste products that are supposed to be eliminated by the specific organs and body’s systems.

It is composed of blood cells suspended in blood plasma which represents the 55% of blood fluids and is mainly constitute by water, in addition to proteins, glucose, minerals ions and carbon monoxide, result product of the respiration during which oxygen reacts with organic compounds to release water and CO2. The blood cells are mainly red blood cells, or RBCs, or erythrocytes, white cells, or WBCs, or leucocytes, and platelets, or thrombocytes.

The erythrocytes contain hemoglobin the iron-binding protein responsible of the transport of oxygen to the cells in all Vertebrates, carbon monoxide is transported instead outside the cells as bicarbonate ion through the plasma.

Coagulation and Hemostasis

The coagulation is the response to a broken blood vessel and the conversion of blood from a liquid form to a semisolid gel to try to stop the bleeding process. The cells responsible for this process are the platelets and other components like the clot factors or coagulation factors.

Blood is a fluid, but its consistency can vary to an almost solid status of a gel. It can be also defined as a suspension of cells inside a liquid that delivers oxygen and vital nutrients to the cells through the circulatory system.

Coagulation is a cascade of events that leads to hemostasis; there are two different pathways, intrinsic and extrinsic which originate separate but then converge at specific point leading to fibrin activation. The extrinsic pathway is activated by external trauma that causes blood to escape from the vascular system, this pathway involves Factor VII. The intrinsic pathway is activated instead for internal trauma by platelets, it involves Factors VIII, IX, XI, XII, common pathways include Factors I, II, V, X.

Coagulation factors are essential to normal blood clotting, their absence, or decrease can lead to bleeding disorders while the increasing in number to abnormal clots. The body produce a blood clot to stop the bleeding, after the bleeding stops the body breaks down and removes clots.

The coagulation factors are twelve and are indicated with Romans numbers, they function in a cascade series of events which involves other molecules and cofactors.

The Coagulation Factors

Factor I, or Fibrinogen, common coagulation blood marker, is converted into Fibrin through the action of Thrombin, deficiency of this factor causes Afibrinogenemia and Hypofibrinogenemia which manifest, of course with bleeding problems. Factor II, or Prothrombin, is converted in Thrombin in the common coagulation pathway. Factor III, or Thromboplastin, other typical coagulation factor activates factor X. Factor IV represents Calcium which is required in many stages of coagulation. Factor V is in plasma but not in serum, is involved in both intrinsic and extrinsic pathways of coagulation and causes the cleavage of Prothrombin in the active Thrombin, its deficiency is cause of Parahemophilia. Factor VI is not more included in this cascade of factors.

Factor VII, or Proconvertin is a stable factor in serum and plasma which participates in the extrinsic pathway with the activation of Factor X in cooperation with Factor III, its deficiency is involved with vitamin K deficiency and so with hemorrhagic tendency. Factor VIII, or Antihemophilic Factor is a labile factor involved in the intrinsic pathway which behaves as cofactor in the activation of Factor X, its deficiency is associate to an X-linked recessive trait that results in Hemophilia A, the classic Hemophilia. Factor IX, or Plasma Thromboplastin Component, or Antihemophilic B is a stable factor involved with intrinsic coagulation pathway, activates Factor X, its deficiency is involved with Hemophilia B, or Christmas Disease and is treated with purified preparations of the factor from human plasma ore recombinant, or Factor IX Complex.

Factor X, or Stuart-Prower Factor is a labile factor involved in both pathways, activated combines with calcium and phospholipid to activate Factor V to form Prothrombinase which cleaves and activates Prothrombin to Thrombin. Factor XI, or Plasma Thromboplastin Antecedent (PTA), or Antihemophilic Factor C, is stable and involved in the intrinsic pathway to activate Factor IX, its deficiency results in Hemophilia C. Factor XII, or Hageman Factor, is stable and activated by contact with foreign agents, is involved in the intrinsic pathway to activate Factor XI. Factor XIII, or Fibrin-stabilizing Factor, is a factor that polymerizes Fibrin monomers enabling fibrin to form blood clots, deficiency causes Clinical Hemorrhagic Diathesis.  

Causes, Complications and Disease Associated with Abnormal Clotting

Some people get too many clots or their blood clots abnormally. Reasons for blood clotting abnormally, or hypercoagulability are different, like genetic disorders, cancer, atherosclerosis, diabetes, atrial fibrillation, overweight, obesity, dehydration, metabolic syndrome, stroke, some medicines as birth controls pills, or any other type of steroid’s medications, sitting in one position for long time as when driving for long distance or travelling in plane.

Two type of cancers are associate with hypercoagulability, Polycythemia Vera, which is a blood cancer that originate in the bone marrow and that cause the production of too many blood cells, all types, causing blood clotting, and Multiple Myeloma which cause increasing number of white blood cells.

Blood clots can form everywhere in the body, a clot in deep veins is called Deep Vein Thrombosis, or DVTs, symptoms associate are swelling, redness and warmth of the area, leg cramps in calves, if a clot travels through the bloodstream to the lungs it causes Pulmonary Embolism, other complications include, strokes, heart attack and kidney problems, peripheral artery diseases, or PAD, anti-phospholipids syndrome.

Blood clots are also a critical complication of Covid-19, cause of strokes and all other type of consequences that we all know very well now, it looks like based on reports that the most severely ill patients present hypercoagulability and Disseminated Intravascular Coagulation, or (DIC), which is a massive intravascular clot production. Therefore, coagulation tests may be useful to discriminate severe cases of Covid, same as for some of the vaccine’s risks and side effects.

The mechanism of the coagulopathy in regard of the infection from the Coronavirus are not still clear, it is speculated that the dysregulated immune response triggered by the inflammatory cytokines, lymphocytes cells death, hypoxia and endothelial damage are involved.

Factor V Leiden is one of the factors involved in coagulation process, it is a result of a mutation which increases a person risk of blood clots, especially in deep veins, the additional risk is due to its resistance of being deactivated by the protein C that keeps normal Factor V activity under control. Protein C and S deficiency are hereditary deficiency, people with these are at risk of blood clotting.

Prothrombin gene 20210A mutation is another genetic disorder associate, people with this have too much of blood clotting Factor II, or Prothrombin, one of the factors that allows blood to clot properly, with too much of this high risk of blood clots.

Symptoms, Therapies and Natural Remedies

Usually there are not symptoms with blood clots, but occasionally people may experience, blurred vision, headaches, easy bruising, high blood pressure, lack of energy, shortness of brief, menstrual bleeding with clots. Recurrent pregnancy loss are also reasons to be concerned about thick blood.

Therapies for blood clots includes blood thinner, as warfarin or coumadin, or anticoagulants like aspirin, or any other natural remedies with blood thinning properties like fish oil, garlic, ginger, turmeric or curcumin, bromelain and so on, B-vitamins and methylated folates and B-12 vitamins are also useful to lower homocysteine, other cardiovascular associate marker, another supplement suggested is nattokinase, a Japanese product, lemon, pineapple, cinnamon also are elements that support fluidification of blood, and water, of course.

Medications are prescribed only with increased risks, many people with thick blood never experience blood clots and this is the reason why doctors usually only recommend lifestyle changes like, quitting smoke, losing weight, exercise, and avoiding long time in same position.

Blood Consistency or Viscosity

Blood consistency should be not too thin to cause bleeding, but also not too thick to cause clots, this property is defined as viscosity, and represent a measure of a fluid’s resistance to flow; it is important to know the type of blood consistency or viscosity to prevent consequences, to address therapies, lifestyle, and supplementation.

Thick Blood

Thick blood is caused by heavy proteins load or by too much blood in circulation, too many red and white blood cells, and many platelets or thrombocytosis, and from imbalance of the blood clotting system made of clotting factors and other components.

For heart and circulatory system thinner and more watery blood might be better than a thicker or more viscous blood that can cause more risks for heart attack and stroke.

There are more agreements in regard of the fact that watering down our blood can prevent heart disease, a quote from the Harvard Education School states that, “The more viscous the blood is, the harder the heart must work to move it around the body, and it is more likely to clot inside arterial and veins”.   

Viscosity is also associate with high cholesterol and blood pressure, and can be controlled by drinking enough water, more statements in regard of something that looks so obvious and so simple, and the reason why naturopaths keep reminding of drinking enough water, not simply to hydrate but for its multiple function.

How much blood is thin or thick it depends on many factors. The red blood cells have the major influence since they account for half of the volume of total blood. The hematocrit is a measure of the number and size of RBCs, its number in % account for percentage of blood volume occupied by red cells.

Blood fats such as LDL affect viscosity, the more LDL the thicker the blood is, same thing with fibrinogen, soluble protein, coagulation marker that can be transformed into insoluble fibrin, the basis for blood clots. Chronic inflammation also increases the viscosity of blood, so as smoking, high levels of homocysteine, high level of platelets and clotting factors, diabetes, and genetic disorders.

Laboratory’ s studies generally link blood viscosity with cardiovascular markers, and more studies have shown that people with highest viscosity are more prone to develop heart disease and that statins therapy decrease viscosity with long term use, but not all studies convene on this last connection, as we all know there are multiple alternatives today for reducing blood viscosity and the risks related.

To mention an example from conventional medicine point of view a book titled “The blood Thinner Cure” written by a cardiologist, Kenneth R. Kensey talks about “The Sludge Factor” and enlists several steps to thin blood like quitting smoking, eating healthy diet to lower LDL cholesterol, reducing stress, taking low dose aspirin, donating blood, or drawing blood for blood tests, or phlebotomy therapy, drinking 10-12 glasses of water per day.

Thin Blood

Thin blood or thrombocytopenia, due to decreased number of platelets is less common than thick blood. Chronic bleeding and excessive bruising may be caused by overly thin blood.

Hemophilia and Von Willebrand’s disease are two medical conditions due to the missing of clotting factors in the first case, and because blood platelets lack a sticky coating, women with Von Willebrand’s disease may have heavy periods. People with thin blood are given blood thickeners before of a surgery to prevent bleeding complications.

Reasons for decreased platelets production are viral infections, bone marrow disorders, leukemia or lymphoma, disorders of spleen, some autoimmune diseases like RA or SLE, chronic liver disorders, or physiologic factors like aging and pregnancy.

Signs are bleeding gums, nose bleeding, blood in stool, heavy menstrual periods with clots, bruising, causes are those mentioned above, or overuse of aspirin and pain killers.

Therapies for bleeding disorders vary based on site of bleeding and are different and specific for each casualty, for bleeding nose for example there are different remedies and the most are of local application and of pressure and tamponing of nostrils, for other type of bleeding steroids as estrogens and progesterone are suggested, or natural remedies like sugars or salts or herbal elements. Medications for bleeding are not easily prescribed for the risks associated, and side effects.

Thanks For Reading

Mariarosaria M.

Sources:

Harvard Educational School

Medical News Today

Medline Plus

Weber Educational

http://www.insidescience.org

Picture by futura-sciences.com

Global Cancer Symposium Review Part II.

New Findings in DNA Repair May Lead to Cancer Inhibitors
Picture by sciencenewsjournal.com

This part includes even more interesting data, more types of techniques utilized, new tests and promising therapies.

Dr. Bita Badakjhan, M.D.  has been providing some of this useful information while talking about “Avoid Metastasis and recurrence of cancer.”

We all have tumor cells, she says, but if not activated from any oncogenic process or metabolites they remain harmless; secreting tumor cells and growing process takes up to six years to be manifested. At the begin tumor cells circulate in blood to reach organs and systems.

It is possible to know if these cells are circulating in blood ahead of time doing a liquid biopsy called RGCC test or Greek test; this is not still available in USA, but it is coming soon, only countries as Germany and Greece practice, and so centers associate send their samples to be analyzed. They look at tumor and stem cells, circulating cells are from time in body, stem cells may show few mutations but not still cancer development; they might also show presence of virus and parasites or any other infection that may cause cancer; no symptoms must be ignored.

Microbiome is the key to fix everything and so tumors. Immunotherapy, fico transplant, acidity tests, rebuilding of microbiome, restore of mitochondria, get rid of toxins, those the things she was suggesting, so as many other doctors; additionally, in regard of microbiome health she was reminding of not giving antibiotics to kids because here is where imbalance begin and the whole series of problems.

Regular biopsy causes cancer cells daughter to spread all over the body. Cryotherapy freezes tumor in situ then to be removed, chemo is necessary in worse cases, not suggested antioxidants during chemo because they can neutralize effects of chemo, but after a week to rebuild the immune system suppressed from chemotherapy, or prior a chemo. Hypothermia or hyperbaric oxygen also are better before of chemotherapy.

Best diet for this doctor is vegan, to avoid estrogen in animal production. Cancer likes pH 6.5-7.5, ideal pH should be 7.5-8.5. Cancer cells produce lactic acid, this the reason why they make cells so sick. She was warning against radiations, avoiding X-Ray tests too frequently, and in support to supplement with NAC and SOD.

Other tests they practice at her clinic, “The Healing center for Cancer”, I believe is called PHI, is a blood work and stand for Phosphohexose Isomerase; it is an enzyme of fermentation, anaerobic marker of anaerobic metabolism, and is produced by cancer cells, if is elevated, the body is going to form cancer.

This test can be done before of RGCC test.

If PHI test is done after chemotherapy means cancer is going in metastasis, in this case patient is treated with hyperbaric oxygen, alkaline environment, IV high doses of vitamin C; these therapies may not work for everyone. Circulating cancer cells can be still circulating even after a diagnosis of remission until the root cause is found.

It is particularly important to keep stomach acidity because microbes, especially parasites can cross the gastrointestinal barrier and reach out organs and multiply for years, not a good idea to drink alkaline water while eating if there is acid reflux, acid is necessary to digest food, and mainly proteins, and for this reason it is especially Important to know about food allergy, sensitivity, and intolerance to prevent acid.

Dana Morgan, other speaker, was mentioning the RGCC test, and that treatments following the results are personalized.  IPT, or low dose chemotherapy is combined with other things to support the immune system, like herbs and nutrients. She also mentioned that the Journal of Oncology was stating that chemo, radiation, cannot eradicate a cancer, but instead for 90% causes metastasis, and that Western Medicine is linking HPV and Epstein Barr to lymphoma and prostate cancer, but eventually there are more connections among viruses and cancers. Immunotherapy is especially important and virus eradication.

Dr. Leigh Erin Connealy, M.D. also member of “Cancer Center for Healing” was illustrating the Nano Oxygen and all therapies with oxygen, hyperbaric, ozone therapy, etc. Bath in nano bubbles plus oxygen. We need oxygen for everything, every reaction in our body needs oxygen. How relate to cancer, Otto Warburg, German scientist discovered that cancer cells thrive in anaerobic environment, for oxygen is definitively an enemy for cancer cells.

John Santoyo, technician was talking about another technique, the SEP, Electrohydraulic Pressure Pulse for reversing cancer polarity. This device produces strong pulses that can be felt in body, based on lithotherapy principle, and good for kidney stones too. Cancer is an electrical fault, every organ has positive and negative electric poles, cancer tries to hide from the body’s immune system developing a fibrinogen tissue around itself that helps to hide and reverse polarity. This electromagnetic device is also good for many other issues like, muscles, endocrine, adrenal fatigue, plantar fasciitis, and foot disorders, and for healing wounds, thanks to the waves coming from the pressure.

Dr. Ben Edwards, M.D., was speaking about “Affordable, safe, and effective treatments when money is tight”. He was a family prime care doctor, but then changed his prospective after a celiac patient began to be better after radical changes of diet and lifestyle since he saw a naturopathic doctor. Still some doctors can prescribe supplements but do not look at root causes, he thinks.

Insulin balance and mitochondria health are the most important pillars of health for this doctor.

Cancer is not acquired, such as a virus like the coronavirus of Covid-19, for example, but both emerge in a drastic inflammatory status, or chronic disease, metabolic inflexibility, terrain dysfunction.

And then he was analyzing the germ theory versus terrain theory, germs are part of the problem, but if we only eliminate them we do not solve the problem, for example he was referring to insects and mold, if they are only clean out away, they will grow again; it is necessary to keep the environmental conditions (pH, ventilation, hygiene) for do not let them reproduce; same thing with COVID-19 and all other germs, it is all about the terrain.

Genes are turned on when all is exhausted, if there are chronic or inflammatory conditions, or comorbidity he suggests starting a fast, or low blood sugar diet, increasing vitamin D levels, (as cod liver oil, or sunshine), managing stress, and use of anti-inflammatories like vitamin C and ozone.

If no symptoms with a COVID-19 infection means that the immune system is working the way should, so it is a good thing. During a liquid biopsy there are circulating cancer cells because we all have, the matter is to keep these repressed and not multiplying and developing tumor with appropriate lifestyle and effective immune system. People can have tumor for years that does not change, in many cases cancer does not cause problems, there are more instead with conventional treatments.

His 4 pillars are: nutrition, hydration, movement, and peace.

Nutrition must be plant based and organic, he was stressing on the importance of salts and minerals, and reducing sugar content foods and all inflammatory foods, applying a narrow eating window, with intermitting fast, at least of 16 hrs.

For hydration, not just water but also type of foods hydrated, like watermelon for example or any type of fruits and vegetables, in this water is structured, H3O2, which means that will penetrate in cells membranes better. If urine are too yellow means that we are not hydrated, if they are clear like water we are hydrated, better clean water mineralized, from rain and spring sources.

For movement, simply regular movement, if at home and smoking and then go to the gym, not useful, better being outside.

For peace he meant to stay away from negative thoughts which release negative energy and abnormal vibration frequency. God drives us through this life, deep spirituality, “you are the cure, your body has the power to heal.”

Donna Gate was treating, “Candida, parasites, and cancer, removing infections to facilitate and achieve healing”.

She is the author of the “Body Ecology Diet” written to overcome candida infection. Candida, parasites, and cancer are all connected.

Parasites are difficult to get rid of, they hide in biofilm in small intestine for years, only colon therapy can eliminate them pouring water slowly to fill the colon so that the biofilm can be detached from the walls, those in large intestine can be eliminate through colon cleanse and detoxification processes. Candida can be local and systemic. Can be managed with treatment, diet and immune system reinforce, but not cured.

Candida presents in two forms, as yeast, not aggressive, and as filament with tentacles called ife; both produce toxins, gliotoxins and acetaldehyde, this last one is a byproduct of alcohol, reason why people with candida infection may look like drunk or sleepy because acetaldehyde can affect the brain. Toxins damage DNA, DNA damaged causes cancer, cells die or mutate. Too many senescent cells commit suicide, apoptosis, and so a tumor.

Causes are, high sugar diet, weak immune system, stress, antibiotics, estrogen dominance, alcohol, chronic inflammation, oxidative stress, ROS, and free radicals, superoxide, hydrogen peroxide, ammonia, processed foods, sugars, and bad oils. Genes involved, SOD, CAT, CBS, GSH, and variants in the ATP cycle.

With aging, inflammation, apoptosis, and immune resistance there is a gene that modulates these processes in a positive way. DNA repair gene SIRT-1-7 controls circadian clock, and how cell respond to stress, to niacinamide, and resveratrol.

We can increase Sirtuin for longevity with deep sleep, autophagy, calories restriction, polyphenols in bitter vegetables, oil of olive, dark chocolate, curcumin, ginger, ginseng, dark berries, DHA, melatonin, NADH.

Diet for candida besides sugars and carbohydrates must avoid oxalates foods, high histamine foods, and animal proteins, yeast converts amino acids in putrescines. Sugar feeds cancer, yeast makes oxalates (defense systems for plants) which are toxins that produce stones, and they cause pain everywhere they establish. Histamine also related, wine and fermented foods contain histamines, also chocolate and soy, but miso soup seems to prevent breast cancer.

Her conclusions, fix gut, remove candida and parasites and biofilms, bad diet and toxins, repair gut lining and regenerate microbiota. Support genes variants: ALDH, ALD, alcohol clearance, detoxification, methylations pathways, CBS, GSH, IL-6, inflammatory cells, all SNPs for nutrients. 

As we can see plenty of recommendations, some over-repeated and well known, especially for who is in the field, or worse involved with cancer personally, but also many new and important information.

Thanks for reading.

Mariarosaria M.

Global Cancer Symposium Review

Cancer: When good cells go bad | CTCA
Picture by cancercenter.com

“Revolutionary new treatments in Alternative Medicine, encouraging resolutions and radical remissions.”

These the most remarkable aspects and facts to collect from this symposium.

The host, Nathan Crane after difficult life experience and wrong lifestyle discovered new ways to be healthy and from here, he became always more involved with alternative medicine; at this time, he is interviewer, film producer, and Award winner director of the healing club “Cancer, The Integrative Perspective”.

He is the organizer of this symposium which gathers a variety of scientists, mainly alternative medicine doctors talking about cancer, new techniques, and strategies in alternative medicine to prevent and to cure, not just cancer but all the inflammatory diseases.

All the speakers were providing interesting information, conversations were professionally managed with no interruption from the host and questions were appropriate and investigative.

Dr. Robyn Benson, D.O.M.  member of the “Cancer Center for Healing” was talking about therapies and of regenerative medicine, how to reverse from degeneration through oxidative medicine and stem cell therapy. She was giving much importance to mouth hygiene, many diseases come from the mouth and from there spread to the whole body. In connection to this Dr. Benson was emphasizing technique like hydrogen peroxide and ozone therapy as oxidative therapies to get rid of microbes as root cause for cancer. She also was speaking about the importance of the environment and necessity to get rid of toxins, detoxification protocols, and much more the importance of being surrounded of indoor plants to generate oxygen to detoxify from environmental toxins, and for all what we need oxygen for. Negative thoughts affect all systems and so the wellbeing, it is especially important therefore maintaining a healthy mental status, feelings, and emotions during a disease to support the healing process.

Dr. Kelly Turner, PhD was discussing about radical remission and that healing from cancer is possible without conventional medicine. She classifies 3 categories of people, 1) those who refuse from the begin to be treated from conventional doctors, 2) those who begin with conventional treatments but then discouraged of results decide to contact alternative doctors, 3) and finally those who combine conventional treatments with integrative medicine.

As alternative therapies she was mentioning besides the “Gerson Diet” as type of diet for cancer, “Coley’s Toxins” injections where a mix of killed bacteria are injected to stimulate the immune system, while other doctors are incorporating high doses of vitamin C with low doses of conventional chemotherapy, or LDI.

Among her 10 pillars, as for the most of these doctors, there are, diet and exercise, toxins avoidance and detoxification, herbs and supplements, stress reduction, sleep and meditation, positive attitude, social interacting and support and spiritual practice.

All the relaxing techniques release substances that increase the production of natural killer cells, lymphocytes-T class of cells that reinforce the immune system, but also increase telomeres length, for life extension and rejuvenation.

The 10 healing factors do not guarantee healing in all cases because each case is different, but for sure the strength of the immune system. Most important of everything is to have a purpose in life and to be forgiving, to have compassion, love, kindness, and gratitude.

Dr. Tom O’Brian, N.D., was reporting about “Altered Microbiome: Optimizing Gut Health and Ability to Fight Cancer.”

He was mentioning 5 pillars for keeping healthy, and not just for avoiding cancer, but all the diseases, and mainly to control inflammation. These 5 pillars are, the food we eat, sensitivity and intolerances, the environment and toxins, the microbiome balance, the intestinal permeability o leaky gut, the genetics. It is important to avoid doing same things that are the cause of the disease, it is fundamental to change lifestyle and diet and unhealthy choices.

He was emphasizing Dr. Alessio Fasano’s research, and discover of the zonulin, the marker for leaky gut, or permeable intestine, and the comment that Dr. Fasano makes in relation “Every disease begins in the gut” which, is, of course, the most important and primary thing to address. First thing he suggests to do is to look at food sensitivity and/or intolerance because this is what cause microbiota imbalance and dysbiosis and so gut inflammation and from here leaky gut that compromise the immune system response and all that can derive, from autoimmunity to cancer.  Some of the comparisons he does to explain the leaky gut and the whole process are typical, and well described in his two books. “Autoimmune Fix” and “Fix Your Brain”, both excellent books.

Substantially he defines as “cheese-clothes” the pores that can be created in the intestinal wall due to the permeability process caused by the inflammatory molecules and toxins released from bacteria, like the LPS of the cell coat of Gram negatives bacteria. Undigested macromolecules, due to lack of digestive enzymes, or of hydrochloric acid, or to intolerance across these pores of the intestinal barrier disperse in blood and so in the body system. The immune system does not recognize these molecules and begins to attack and create more inflammation, or if these molecules, which practically are sequence of amino acids, have a similarity with the structure of a tissue or an organ, the immune system will attack its own tissues and organs (molecular mimicry), and from here starts the degeneration process and so autoimmunity, o cancer, or other diseases.  He widely treats these subjects in all his videos, webinars, classes, conferences, and public appearances.

Natasha Zalos, technician, was talking about lymphatic massage and technique that uses a device as a form of therapy, not only for cancer but for all the inflammatory conditions; every time the immune system get compromised the lymphatic system drains the fluid with toxins, dead cells and microbes away from the body, but when people are not well this system does not function as should and so this type of technique and massage done with essential oils will help to release these toxic load from the body.

Dr. Thomas Lodi, M.D. began introducing “what is cancer” itself and investigating “beyond rapid cells growth”.

On his definition cancer is the capacity to disturb “homeostasis” which means balance in body, to heal cancer, or other diseases it is necessary reestablishing the balance; for example, if blood pressure is not balanced for a variety of reasons, more than lower down with medications or other remedies it is necessary to discover and eliminate the cause (stress, diet, not exercise, environment), people with years of hypertensive episodes are at risk of hypoxia and so also from cancer because cancer develops in anaerobic environment, and which means in absence of oxygen.

All cells need energy for their functions, and 50% of this is used for building process, the machinery of energy in our body are the mitochondria where ATP, the universal molecule of energy is produced, and for these reactions to happen oxygen is necessary, oxidative phosphorylation is the stage of metabolism where these molecules are produced. Oxidation will produce free radicals which if accumulate will cause mitochondria vulnerability; with the aging process and degenerative processes 40-50% of cells become dysfunctional, loose mitochondrial function, and start to ferment.

Cancer is a chronic fermenting cell, same process for all type of cancers, dead tissues, food for bacteria, necrosis, glycolysis, lactic acid, CO2, sore muscles; if we exercise for long time and experience fatigue and shortness of brief, fermentation is happening.

Each cancer, he states, has a cause correlated besides the genetic, and gives much importance to prebiotics and diet which must be vary with lots of antioxidants to function as anti-inflammatory.

Glutamine and glucose are inflammatory, cancer cells feed on glucose, intermitting fasting it is necessary to keep healthy besides all the other roles more time mentioned and basic for all, food, hydration, sleep, exercise, air quality, environment, toxins, stress, meditation, spirituality.

Dr. Nalin Chilkov, D.M.O, was talking of plan, team, and cooperation, and understanding the whole picture, if autoimmune disease and cancer it will be more inflammation, if diabetes it will be necessary to balance insulin and blood sugar first. Diet must be low carbs and sugars no way, cancer cells thrive on glucose, and excessive proteins can also fuel cancer.

Plates must be ¾ of colorful vegetables, the remaining of lean proteins and healthy fats, no bread, or pasta, or fruit, lots of vegetables for healthy microbiome and healing mushrooms for support of immune system. Hydration and sleep are especially important, intermitting fast using fluids with electrolytes as water, teas, or broths.

Dr. Daniel Pompa, D.C., was all about fasting. Fasting 101- Truth about fasting and cancer, intermittent fasting strategies, beyond fasting, these were the titles, and I believe “Beyond Fasting”, the title of his book.

One extended fast per year or short intermittent fast can reduce risk of getting cancer 95%. He was explaining the concept of autophagia, when in deep state of fast body eats its own bad cells, bad DNA, inflamed and senescent cells, I believe mainly through the work of macrophages and the other phagocyting cells, for this reason long term fast, even 5 days is a healing process.

He was mentioning Dr. Valter Longo, PhD, Italian scientist, and creator of the “Longevity Diet” or “Dieta Della Longevita” in original Italian, as model for these fasting.

These types of fasting are usually done with water or fluids with proteins, with partial fasting is possible to reach same benefits anyway under 1000 calories per day and 20 gr of proteins per day, water fasting is the best at least once a month.

MTOR which stands for high protocols metabolic pathway, non a good idea for people with cancer.

Diversity in microbiome, change in diet, adaptation of body systems, inflammation treatment, homeostasis balance, cell regeneration, diet variation are the strategies.

Dr. Junil Pai, M.D. “Inflammation and cancer, reduce through lifestyle and natural anti-inflammatories”, this what he was discussing.

Inflammation progress to cancer or other diseases, the key is reducing inflammation wherever and however this is expressing. The underlying mechanisms that are causing chronic inflammation are too challenging to treat if there is more degeneration. Overtime constant inflammation cause degeneration of tissues, and suppresses the immune system favoring cancer development, also persistent infections, and exposure to toxins. The epigenetics has its role, it is important to incorporate correct lifestyle to turn off the bad genes.

Then he was giving some examples, chronic colitis can bring to colon rectal cancer after years of bleeding and inflammation, arthritis not treated from years arises the risk for lymphoma. Always necessary to find the root cause of a disease and let the body heal by itself with the appropriates tools and strategies.

Essentially important for this doctor to treat inflammation, and as anti-inflammatory foods he was suggesting plant-based food diet and organic, phytonutrients like resveratrol, curcumin, and polyphenols, all antioxidants, simply treat with diet.

Top foods pro-inflammatory for him are dairy, which stimulates insulin grown factors, with the age we lose digestive enzymes, raw organic removes toxins but is still non healthy, and dairy produce a lot of mucus. Eggs are to avoid because among the content of cholesterol, risk for heart disease, produce procarcinogen for microbiome. All animal proteins cause dysfunction of microbiome for production of endotoxins causing inflammatory response. Bad Fats as saturated fats well known cause of inflammation, and he was mentioning as example ghee and coconut butter both considered healthy fats, but while ghee even having an animal origin, has lots of benefits including detoxification and capacity to lower lipids, coconut butter instead despite of its benefits and coming from plants can increase the lipids levels.

He made some other considerations in regard of foods considered healthy like for example, salmon for being full of toxins, bone broth which has none of the benefits demonstrated, and ketogenic diet because producing ketones feeds cancer cells that use ketone as fuel as much as glucose; too many proteins and fats as well are non-healthy.

He was mentioning angiogenesis which is the cut of blood supplies to cancer cells, as the most important thing for cancer rather than alternative therapies like IV solutions, they are not so useful if there is not radical change of diet and lifestyle, these are things not easy to accomplish and therefore support is necessary.

As we can see there is always some discrepancy and disagreement, but in general they all agree on major steps and fundamental lifestyle behaviors and mainly in finding the root cause and lowering down inflammation and keeping a healthy microbiome.

There are few more that I have had the opportunity to listen and I am going to review in a next blog.

Thanks for reading.

Mariarosaria M.

To be continued.