Could be worth a read for some, Ivabradine is used to treat angina but appears to cut the risk of death from heart failure by 26%. It lowers heart beat rates without lowering blood pressure and could give a good alternative to the need for beta-blockers for this problem, which not everyone can take, like those with asthma etc.
If you are interested in the full story, then it's here......
http://www.bbc.co.uk/news/health-11127782
New pill may cut heart failure rate
New pill may cut heart failure rate
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Re: New pill may cut heart failure rate
The current 20 peer reviewed but not independent investigations (just checked) suggest this drug maybe an advance but it is new and could just as easily become another new disaster. Keep in mind that the current epidemic of heart failure deaths in the US and a lot of cancer deaths and neurological conditions there are strongly linked to STATIN based cholesterol drugs (this example is particularly pertinent as most cardiovascular disease patients are also given cholesterol lowering medicines despite a near total lack of evidence that they decrease mortality in individuals older than 50, in fact they are associated with decreased survival as is a total cholesterol of <170 even if compared to >400!).
Statins were and still are for those that do not follow or understand medical research also considered an advance, this includes most doctors (health research is a specialised field and very tricky). As a test ask your doctor what they think of statins and the need to keep cholesterol down to 170
).
In reality, statins do 3 principal things 2 of which tend to be fatal and the 3rd is more questionable than most would suspect, these 3 things are:
1. Lowers cholesterol that research does not support unless you are a obese middle aged white with existing coranary artery disease then they may lower coranary artery disease deaths about 1% not the 50% as reported in the Crestor's now successfully litigated and discredited Jupiter study that found a RELATIVE RISK reduction of 50% i.e. 2/1000 to 1/1000 a very poor outcome statistic, ABSOLUTE RISK reduction is better and in the preceding example is 0.001%!!, an even better measure is ABSOLUTE MORTALITY in case the investigated substance kills by mechanisms other than coranary heart disease like Crestor and other statins appear to, a couple of links (many more technical links exist) http://www.drmcdougall.com/misc/2008oth ... estor.html , http://www.nieman.harvard.edu/reportsit ... ?id=100952
2. Blocks CoQ10 production that is needed for energy production and the heart is among the most energy dependent organs in the body > heart failure. Be aware that supplementing with CoQ10 is not a real benefit as it cannot come close to endogenous production.
3. Blocks the formation of dilichols, these substances help DNA maintenance and replication, blocking them > cancer. The former deputy director of the USFDA is on record as stating that in animal models (shorter life cycles) statins are among or the most carcinogenic substances ever tested. Interestingly, every major study has found equal or greater cancer related occurances / deaths in those taking statins and these investigations were only conducted for 5 years
(100 cigarettes a day for 5 years = smoking modern cigarettes appears pretty safe in relation to cancer induction, but longer term studies CERTAINLY do not support this conclusion)
Statins were and still are for those that do not follow or understand medical research also considered an advance, this includes most doctors (health research is a specialised field and very tricky). As a test ask your doctor what they think of statins and the need to keep cholesterol down to 170
). In reality, statins do 3 principal things 2 of which tend to be fatal and the 3rd is more questionable than most would suspect, these 3 things are:
1. Lowers cholesterol that research does not support unless you are a obese middle aged white with existing coranary artery disease then they may lower coranary artery disease deaths about 1% not the 50% as reported in the Crestor's now successfully litigated and discredited Jupiter study that found a RELATIVE RISK reduction of 50% i.e. 2/1000 to 1/1000 a very poor outcome statistic, ABSOLUTE RISK reduction is better and in the preceding example is 0.001%!!, an even better measure is ABSOLUTE MORTALITY in case the investigated substance kills by mechanisms other than coranary heart disease like Crestor and other statins appear to, a couple of links (many more technical links exist) http://www.drmcdougall.com/misc/2008oth ... estor.html , http://www.nieman.harvard.edu/reportsit ... ?id=100952
2. Blocks CoQ10 production that is needed for energy production and the heart is among the most energy dependent organs in the body > heart failure. Be aware that supplementing with CoQ10 is not a real benefit as it cannot come close to endogenous production.
3. Blocks the formation of dilichols, these substances help DNA maintenance and replication, blocking them > cancer. The former deputy director of the USFDA is on record as stating that in animal models (shorter life cycles) statins are among or the most carcinogenic substances ever tested. Interestingly, every major study has found equal or greater cancer related occurances / deaths in those taking statins and these investigations were only conducted for 5 years
(100 cigarettes a day for 5 years = smoking modern cigarettes appears pretty safe in relation to cancer induction, but longer term studies CERTAINLY do not support this conclusion)Re: New pill may cut heart failure rate
Informative reply Morsage, will obviously then have to wait and see with it.
Interesting what you mentioned about CoQ10 and that supplementing it has limited effect as, correct me if I'm wrong, but doesn't the body produce less of it as we grow older? Isn't it essential for basic chemical reactions in all cells and a very strong antioxidant?
If so, then is there any other way get it's benefits (which appear to be many) or promote natural production as we age. From what I gather a deficiency of it can be quite serious.
Interesting what you mentioned about CoQ10 and that supplementing it has limited effect as, correct me if I'm wrong, but doesn't the body produce less of it as we grow older? Isn't it essential for basic chemical reactions in all cells and a very strong antioxidant?
If so, then is there any other way get it's benefits (which appear to be many) or promote natural production as we age. From what I gather a deficiency of it can be quite serious.
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Re: New pill may cut heart failure rate
Spitfire your views on CoQ10 are pretty correct and it also has the added ability to recycle other antioxidants. The problem with supplementing CoQ10 is the bio-availability and safety of these supplements is questionable and lacks sufficient quality research. Further, an increasing body of research suggests that taking isolated antioxidants may imbalance the bodies antioxidant defences and actually increase free-radical related damage. 100's of studies find fruit and vegetable consumption somewhat protective against cancer whilst most single antioxidant supplement research finds increased rates!
CoQ10 is important especially in aging but the best way to get or make it and at a much higher and better balanced dosage is to eat quality protein foods such as meats, fish, nuts, beans, seeds. Especially, beware of poorly balanced vegetarian diets. Interestingly, of the 5000 odd people living to 100 years of age in the UK each year now nearly all are meat eaters with meats and some unrefined cold pressed oils the best naturally occuring sources of CoQ10.
CoQ10 is important especially in aging but the best way to get or make it and at a much higher and better balanced dosage is to eat quality protein foods such as meats, fish, nuts, beans, seeds. Especially, beware of poorly balanced vegetarian diets. Interestingly, of the 5000 odd people living to 100 years of age in the UK each year now nearly all are meat eaters with meats and some unrefined cold pressed oils the best naturally occuring sources of CoQ10.
Re: New pill may cut heart failure rate
Morsage,In reality, statins do 3 principal things 2 of which tend to be fatal and the 3rd is more questionable than most would suspect, these 3 things are:
1. Lowers cholesterol that research does not support unless you are a obese middle aged white with existing coranary artery disease then they may lower coranary artery disease deaths about 1% not the 50% as reported in the Crestor's now successfully litigated and discredited Jupiter study that found a RELATIVE RISK reduction of 50% i.e. 2/1000 to 1/1000 a very poor outcome statistic, ABSOLUTE RISK reduction is better and in the preceding example is 0.001%!!, an even better measure is ABSOLUTE MORTALITY in case the investigated substance kills by mechanisms other than coranary heart disease like Crestor and other statins appear to, a couple of links (many more technical links exist) http://www.drmcdougall.com/misc/2008oth ... estor.html , http://www.nieman.harvard.edu/reportsit ... ?id=100952
2. Blocks CoQ10 production that is needed for energy production and the heart is among the most energy dependent organs in the body > heart failure. Be aware that supplementing with CoQ10 is not a real benefit as it cannot come close to endogenous production.
3. Blocks the formation of dilichols, these substances help DNA maintenance and replication, blocking them > cancer. The former deputy director of the USFDA is on record as stating that in animal models (shorter life cycles) statins are among or the most carcinogenic substances ever tested. Interestingly, every major study has found equal or greater cancer related occurances / deaths in those taking statins and these investigations were only conducted for 5 years
Now you've frightened me. Here is my situation. I was diagnosed with high cholesterol in my late 30's (total cholesterol 280, LDL too high, HDL too low). For three months, I religiously followed the doctor's advice on eating, drinking, and exercising to try to lower it naturally. At the next check the readings were still the same so the doctor told me that in my case it was heredity and I could not correct it with diet and exercise and therefore had to go on a statin. I've been taking Zocor now for nearly 25 years daily and my cholesterol is under 200 if I stick to the prescribed dosage and the HDL and LDL which are still not ideal are considered to be within normal ranges. I am in my early 60's and moderately overweight (not obese) and have no personal history of heart or coronary artery disease. However, every male in the previous two generations in my family (Father, both grandfathers), died of strokes due to blocked arteries (don't know the details of the grandfathers but my dad died of a blocked carotid artery in his neck.
So, what do I do? Live (or die) with high cholesterol or live (or die) because of taking a statin?
My brain is like an Internet browser; 12 tabs are open and 5 of them are not responding, there's a GIF playing in an endless loop,... and where is that annoying music coming from?
Re: New pill may cut heart failure rate
I'm no expert HHF but as far as natural aids for healthy arteries go then you could have a look at grape seed extract or bilberry extract, both reportedly good for circulation health.
Don't know if they are compatible with the drugs you are taking, only a doc etc can tell you that but I've looked into both and they are reportedly very good for you in this section. Bilberry extract increases blood flow by slightly thinning the blood, is supposed to be good for your eyes too.
Maybe drink red grape juice for breakfast too instead of orange juice. However, others may know more on this than me and I know that opinion on supplements and their usefulness can be very mixed.
Don't know if they are compatible with the drugs you are taking, only a doc etc can tell you that but I've looked into both and they are reportedly very good for you in this section. Bilberry extract increases blood flow by slightly thinning the blood, is supposed to be good for your eyes too.
Maybe drink red grape juice for breakfast too instead of orange juice. However, others may know more on this than me and I know that opinion on supplements and their usefulness can be very mixed.
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Re: New pill may cut heart failure rate
Hi HHF, Spitfire's grape seed antioxidant tip tends to be a real benefit, red grape juice not made without crushing the seeds though is of minimal benefit. Hawthorn and Bilberry MAY be beneficial but large doses of omega3 and niacin (see Harvard's page on cholesterol) tend to be REALLY useful.
Following is a review on the clinical use of grape seed antioxidant I prepared last year (THOSE THAT ARE NOT INTERESTED DO NOT READ, this was an academic presentation so is a little technical but not overly so). Further, this information is intended for just general consideration as, this for that cook-book medicine is very low class compared to a developed understanding of an individual's unique biological predicament.
Reflective Practice Exercise: The clinical prescription of Grape Seed Extract for individuals with high cholesterol and unfavourable cardiovascular risk ratios.
Critical Analysis: The practice of employing 12000-24000 mgs. per day of whole Grape Seed Extract (GSE) manufactured by Hilda Hemme Herbals or Blackmores to specifically lower cholesterol and raise high-density lipoprotein (HDL) relative to low-density lipoprotein (LDL) is of considerable importance within my clinical practice upon reflection of my clinical actions and strategies due to:
1. The frequency of high cholesterol (HC) with unfavourable HDL levels and LDL ratios within my new patient pool.
2. Often recommending GSE to replace medically prescribed statins for HC based on assumption of the safety and effectiveness of GSE relative to statins.
3. Contemporary medical belief and practice based on accepting life-threatening consequences of high cholesterol, and afflicted patients' anxiety over their perceived risk of life-threatening cardiovascular events.
4. Personal anxieties related to using GSE for HC and its’ actual benefits and potential risks to my patients, practice and profession. These anxieties principally arise from my current approach relying on information from many sources, including some no longer available, combined with seemingly good clinical results accepted without critical review. Specifically, I assume GSE is safe except for people with grape allergy, is effective in lowering cholesterol, relatively raises HDL and lowers LDL and that statins based drugs have considerable associated iatrogenic dangers.
The foregoing GSE and HC management issues and concerns, highlighted by reflective practice, suggest the need to acquire a contemporary understanding of these issues by identifying and critically examining literature relevant to:
1. The biological plausibility, clinical justification and optimal dosage/s and form/s of GSE for HC and cardiovascular disease.
2. The clinical effectiveness of GSE and its relationship to the clinical effectiveness of statins for HC and cardiovascular disease.
3. Potential benefits, dangers or risks associated with the clinical use of GSE and statins.
4. The relationship of HC to cardiovascular events.
Synthesis: Examination of the preceding analysis reveals the utility of the proposed investigation is primarily dependent on an established relationship between cardiovascular disease/s and high cholesterol and the details of this relationship if present. Cardiovascular risk factors other than those directly related to VLDL, LDL and HDL cholesterol while personally acknowledged will not be considered within this document. Similarly, discussion about the polypeptide Apo(A) fractions of HDL, Apo(B) fractions of LDL and the plasminogen-like lipoprotein Lp(A) composed of apo(A) and apo(B)100 that is strongly associated with cardiovascular disease and resistant to most cholesterol lowering medicines except Niacin will not be specifically detailed (Pagana 2008 pg 106-108).
Cholesterol and Cardiovascular Disease: Contemporary medicine accepts a pathologic role of elevated cholesterol in the genesis of arteriosclerosis and coronary artery disease in which, elevated LDL and very low-density lipoprotein (VLDL) penetrate the arterial wall by oxidative processes. Oxidised LDL and VLDL are cytotoxic to endothelial cells and chemotactic to monocytes which promote their migration into the intima and sub-intimal compartment of arteries and the accumulation of lipids in foam and smooth muscle cells. Trapped foam cells die with an oxidative burst while lipid laden smooth muscle cells become hyperplastic and may bulge into the lumen exposing the sub-endothelium to platelet aggregation, mural thrombi formation and promote arteriosclerotic plaque. These plaques can progress to frank arterial stenosis or occlusion and become stable by calcifying or spontaneously rupture and cause coronary artery disease (CAD) or acute ischemic events, including life-threatening myocardial infarction, cerebral vascular accidents and pulmonary embolisms. (Beers & Berkow 1999 pg1655-6)
Total cholesterol equals VLDL plus LDL plus HDL. As most cholesterol is LDL high serum cholesterol is associated with CAD. Many laboratories only report total cholesterol, triglycerides and HDL. These measures allow calculation of VLDL by dividing triglycerides by five if <400, and LDL by subtracting HDL and the calculated VLDL value from total cholesterol. Elevated LDL and VLDL cholesterol levels are directly related to CAD whereas elevated HDL is inversely related regardless of sex, age and ethnicity. Understanding lipoprotein fractions within total cholesterol provides a more accurate assessment of a patient's coronary risk than consideration of total cholesterol. (McPhee & Papadakis 2009 pg 1095-6)
There are 5 classes of HDL 2a, 2b, 3a, 3b and 3c, only 2b is capable of reverse cholesterol transport and cardio-protection. HDL <40mg/dl is associated with low 2b, 40-60 minimal 2b and if >60 2b tends to dominate the HDL profile, 2b can be increased by cholesterol lowering Niacin but not statins. LDL has 7 classes, from the largest to the smallest; 1, 2a, 2b, 3a, 3b, 4a and 4b. The most commonly elevated LDL’s are 3a and 3b which are small enough to penetrate endothelial cells and promote atherosclerotic disease. LDL4 is especially dangerous, if >10% of total LDL nearly all patients have vascular events within months. VLDL is reported less arteriosclerotic than LDL, but can be converted to LDL within muscle cells, VLDL >25% of total cholesterol is a cardiovascular risk factor. The cardiovascular risk ratio, total cholesterol to HDL, ideally should be 3 and if >5 indicates increased cardiovascular risk. (Pagana 2009 pg 598-600)
Lowering cholesterol reduces cardiovascular mortality and events in patients with known arteriosclerosis but not in patients without arteriosclerotic disease (Beers & Berkow 1999 pg 1656: McPhee & Papadakis 2009 pg 1096-9). Recent Thai public health statistics report cardiovascular related deaths to be the third leading cause of death in Thailand after cancer and poisoning plus accidents (Ministry of Public Health 2007 pg 46).
Treatment to lower cholesterol is currently recommended if there is a genetic propensity or familial history of CAD, premature arteriosclerosis, very high LDL or triglycerides, or very low HDL (McPhee & Papadakis 2009 pg 1095-6). The American Heart Association recommends total LDL below 100 mg/dl and not above 160 mg/dl, has no definite goals for HDL and triglycerides but states HDL <50 mg/dl and triglycerides >150 mg/dl are criteria for metabolic syndrome (Lichtenstein et.al 2006 pg 84). The cardiac risk ratio offers a useful index to monitor patient's risk trends but tends to overstate the protective effects of increasing HDL at low levels (McPhee & Papadakis 2009 pg 1097) and not reliable without considering other risk factors including obesity, smoking, hypertension and diabetes, as high LDL and low HDL are independent risk factors for cardiovascular disease (Gordon et.al. 1989, Kapur et.al. 2008).
The foregoing analysis is based on recent medical texts (Beers M.H., Berkow S. 1999, McPhee & Papadakis 2009), recommendations of the American Heart Association (Lichtenstein A.H., et.al 2006) and the research reviews cited (Gordon et.al.1989, Kapur et.al. 2008) and suggests there is a strong relationship between high LDL or VLDL and low HDL cholesterol with cardiovascular disease.
Cholesterol, Statin Drugs and Hypercholesterolemia: Cholesterol is essential for health and needed to synthesise; bile acids, vitamin D, steroid hormones, stabilise cell membranes, myelin and immune function (Ellison 2006). Further, cholesterol comprises >half the dry weight of the cerebral cortex and is vital to neurological function and serotonin metabolism (Fallon & Enig 2004). As stated in the preceding section, there is some evidence that lowering high cholesterol decreases cardiovascular events or mortality in arteriosclerotic patients but not in patients without arteriosclerosis. However, numerous epidemiological studies report increased mortality associated with low or lowering cholesterol (Ellison 2006, pg 5-7). The apparent disparity between decreased cardiovascular events or mortality and increased mortality appears to arise from reporting different measures and study populations.
Studies reporting decreased cardiovascular events or mortality usually report relative rather than absolute risk while those reporting increased mortality report total mortality a much stronger measure of actual effect (Ellison 2006 pg 5-8, 10, 12,13). Similarly, studies finding decreased cardiovascular mortality associated with low or lowering cholesterol tend to suffer age and gender biases by reporting study populations composed of nearly exclusively middle aged males (Ellison 2006 pg 8,9: Walsh & Pignone 2004). Whereas the numerous studies finding increased mortality associated with low or lowering cholesterol cited by Ellison (Ellison 2006 pg 5-7) suffer age and selection biases by reporting elderly or disease specific populations. Collectively, the foregoing suggests that the preventative role of statin drugs for cardiovascular mortality is poorly supported by research except for middle aged males with known arteriosclerotic disease and that statins appear hazardous for the elderly.
Despite statins reliably lowering cholesterol they do not prevent early death from heart disease, heart attack or stroke (Ellison 2006 pg 13) or slow arteriosclerotic plaque formation (Hecht & Harman 2003). Statin drugs lower cholesterol by inhibiting HMG-CoA reductase, this enzyme is involved in both the formation of cholesterol and substances involved in important biochemical functions including Ubiquinone (CoQ10), squalene and dilochols. The heart requires high levels of CoQ10 which has a critical role in energy supply via ATP production and cell respiration, nerve conduction, muscle membrane integrity, collagen and elastin formation (Fallon & Enig 2004). Dilochols are very important as they organise DNA synthesised proteins and cellular responses, while squalene demonstrates anti-cancer effects (Fallon & Enig 2004).
Statin's most common side effects are muscle pain, weakness and wasting or rhabdomyolysis precipitated by CoQ10 depletion (Fallon & Enig 2004). Heart failure deaths in the United States of America >doubled between 1989 and 1997 after statins were introduced in 1987. 2/3 of 20 patients with normal hearts given 20mg of Lipitor developed abnormalities in cardiac filling within 6 months and 8 of 9 other human studies investigating statin induced CoQ10 depletion found depletion with left ventricular function declines and other cardiac abnormalities (Langsjoen 2003). Neuropathic dysfunctions including polyneuropathy related weakness, tingling sensation, balance and walking difficulty are common in those taking statins for more than 1 year and often irreversible (Fallon & Enig 2004). Psychomotor, cognitive and memory impairments are also common in those taking statins (Tatley & Savage 2007) and reported in several statin studies (Fallon & Enig 2004). Statin related carcinogenesis is found in all rodent studies to date at dosages comparable to human exposures, but human studies are inconclusive due to a lack of follow-up investigations with most human cancers developing over long time frames (Newman & Hulley 1996). Lung cancer takes decades to develop even in heavy smokers, despite this several controlled statin trials do report increased rates of cancer in the statin samples (Ellison 2006 pg 19). Statin induced hepatic failure and hepatitis is not uncommon especially in the elderly (Tuteja et.al 2008). Several other statin related side-effects appear wrongly reported (Fallon & Enig 2004: Ellison 2006) including depression, suicide, immune compromise and premature death as investigation of the source materials cited and or related searches finds these events appear more linked to low cholesterol rather than directly related to statin drugs.
The findings reported in this section are primarily based on two sources (Fallon & Enig 2004: Ellison 2006) both of which exhibit strong bias against statin drugs and at times were found to misreport their supporting literature. However, the aspects reported here are believed valid after reviewing their sources or performing and reviewing database searches for related information. In summary, statin drugs' cholesterol lowering properties are undisputed similar to their inhibiting effects on CoQ10, squalene and dilochol metabolisms. Statin's primary and secondary effects have experimental, epidemiological and biological plausibility to precipitate dangerous side-effects including heart failure, multi-faceted neurological dysfunctions, cancer and liver failure. Increased surveillance for the occurrence or exacerbation of these conditions appears warranted in patients taking statin drugs as does CoQ10 supplementation.
Grape Seed Extract, Hypercholesterolemia and Cardiovascular Disease: Epidemiological studies show much less CAD despite otherwise similar risk factor profiles in those who consume red wine or the polyphenolic flavonoids resveratrol from grapes or proanthocyanidins from grape seeds (Das et.al. 1999). Grape seeds are one of the best known sources of polyphenolic flavonoids (Ghosh & Scheepens 2009) which improve endothelial function, inhibit platelet aggregation and increase LDL oxidation protection in humans (Folts 2002). Wine taken with food reduced postprandial rises in lipid hydropreoxidases and LDL oxidation, GSE proanthocyanidins appear to have the greatest antioxidant effect(Rasmussen et.al. 2005) due to being more specific for peroxyl radicals and ph independent, active within the digestive tract, and inhibit postprandial rises in plasma oxidants as well as lipid deposition (Ursini & Sevanian 2002). GSE compared to grapes, grape juice and red wine shows a greater dose-dependent inhibition LDL oxidation in vitro, in vivo 300mg of GSE was much more effective than 200mg in increasing antioxidant activity (Vinson et.al. 2001). 600mg of GSE is equal to 300ml of red wine or 1250mg of vitamin C in plasma antioxidant activity at 1 and 2 hours after ingestion and significantly increased plasma antioxidant activity with long-term supplementation and reduced total cholesterol, LDL and HDL in subjects with HC but not subjects in normal plasma lipids (Vinson et.al. 2001). 300mg of GSE showed significant increases in total antioxidant capacity in 20 subjects on standardised diets/lifestyle 30 and 60 minutes post ingestion twice daily from the first to the last day, day 5 (Nuttall et.al. 1998).
A randomised double blind placebo controlled study investigating 200mg GSE or 200mcg chromium polynicotinate or both per day found reduced total cholesterol principally from LDL reduction in the GSE -2.5%, chromium -10% and combination -16.5% groups with no significant change in HDL and triglycerides between the groups over a 2 month period. The combination group showed a 20% drop in LDL. Further, 60% of the group receiving GSE showed a >50% reduction of autoantibodies to oxidised LDL compared to only10% in the chromium polynicotinate group (Preuss et.al 2000: Bagchi et.al. 2003). Similarly, 600mg of GSE in a placebo controlled randomised blinded crossover design study of 32 type 2 diabetics over 4 weeks found decreased total cholesterol p=0.05 with insignificant changes in HDL and triglycerides (Kar 2009). These studies consistently suggest that GSE raises the ratio of HDL to total cholesterol by virtue of lowering LDL.
The improved lipid profile effects of GSE have also been demonstrated in many rat and rabbit studies that additionally report a very strong anti-arteriosclerotic effect and other cardio protective actions including decreased platelet aggregation, improved endothelial function and eNOS (Nassiri-Asi & Hosseinzadch 2009: Bagchi et.al 2003 ). However, Clifton reported no significant changes in lipid profiles in a double blinded randomised crossover of control and active ingredient/s study testing 2gms of GSE in yoghurt per day during a 12 week period but did find increased flow mediated dilation in the GSE groups. Clifton's combining GSE with yoghurt, lack of medication and alcohol consumption exclusion criteria, poorly designed diet, and employing several previously undocumented measures suggest caution in accepting his findings in regard to the clinical use of GSE (Clifton 2004).
GSE is proanthocyanidins rich and more importantly they occur in readily absorbable forms including catechin monomers, proanthocyanidin dimers and simple phenolic compounds. Proanthocyanidins appears the most important substances in grapes for cardio protection but a synergistic response from other constituents cannot be excluded. Human inability to digest and metabolise polymeric proanthocyanidins explains why GSE's in vitro responses are often reproducible in vivo unlike the polymeric forms unless injected intravenously that appear more effective in vitro (Ramussen et.al. 2005).
Proanthocyanidins are anti-inflammatory and inhibit monocyte adhesion involved in arteriosclerosis, in vivo, only the monomer and dimer forms are relevant and this effect has been demonstrated in several recent human studies (Ramussen et.al. 2005) in contrast to Clifton's (Clifton 2004) hsCRP, TNF-a, VCAM-1 and ICAM-1 findings. Red wine and grape polyphenols have convincingly shown beneficial vasodilator effects in humans by increasing intracellular Ca activating eNOS, but in vitro results do not find monomer and dimer proanthocyanidins effective only trimers and larger, thus the agent involved maybe a metabolic by-product that has still not been identified. Platelet derived growth factor (PDGF) is a potent mitogenic and chemotactic agent involved in all stages of arteriosclerosis that is inhibited by red but not white wine polyphenols, however enriching white wine with GSE to mimic the mash fermentation of red wine inhibits PDGF suggesting the mash fermentation of red wine releases active compounds from grape seeds.(Ramussen et.al. 2005)
Database searches for iatrogenic, side effects and toxicity with grape seed extract searched on PubMed, US FDA and Australian TGA found no references to noxious effects from GSE. Similar to several animal studies (Yamakoshi et.al. 2002: Wren et.al. 2002: Ray et.al. 2001). Further, I contacted Hilda Hemme the manufacturer of my preferred GSE supplement who confirmed a lack of known toxicity and informed of recent TGA labelling changes wherein GSE 12,000mg capsules can now be labelled 2 per day for the general public.
Summary of Grape Seed Extract Findings: Despite relatively few human trials on GSE it does have an established role in the management of human HC wherein it appears to selectively lower LDL the most undesirable fraction of total cholesterol while maintaining HDL and VLDL. This obviously improves the cardiovascular risk ratio and GSE also has established benefits to endothelial function, platelet aggregation, inflammatory monocyte adhesion and oxidation of LDL. Epidemiological and clinical research research suggests that whole GSE is the most beneficial form despite in vitro findings suggesting poorly absorbed polymeric proanthocyanidins are more efficient. Further, the lack of societal experience and regulatory body findings of toxicity, and the dose responsive nature of GSE effects suggests higher doses in keeping with the current TGA labelling recommendations will be more beneficial than lower doses reported.
Evaluation: This reflective exercise clarified my understanding of cholesterol related cardiovascular disease and specific types of cholesterol's benefits and risks. High LDL and VLDL or low HDL is clearly involved with CAD and life threatening cardiovascular conditions. However, statins's risks appear greater than their benefits for most people and despite GSE not being found in this review to lower total cholesterol as much as statins it has a more selective action against the most harmful fraction LDL and many other cardiovascular and health benefits unlike statins. The dose dependent nature of GSE effects do not rule out the possibility of cholesterol lowering results comparable to statins at the dosage I currently use.
The findings of this exercise largely support my current actions but will allow greater precision in my future management of HC and enhance my ability to provide factual information to patients and decrease anxieties related to HC clinical management. Further, a much wider array of knowledge than described here was gained by performing this exercise that may also improve my clinical efficiency or warrant specific investigation/s.
Conclusion: Reflective practice identified my greatest clinical management concern and helped resolve related issues by addressing my most pertinent professional development needs. Specifically it enhanced my ability to provide better care and interact with other healthcare providers, patients and regulatory bodies in an evidence based format. Further, other issues were identified that will benefit from specific investigation. Reflective practice appears the most efficient and valuable professional development tool available to practitioners by clarifying and accommodating their actual clinical needs.
List of References
Bagchi D., Sen C.K., Ray S.D., Das D.K., Bagchi M., Preuss H.G. and Vinson J.A. (2003) Molecular mechanisms of cardioprotection by a novel grape seed proanthocyanidin extract. Fundamental and molecular mechanisms of mutagenesis: Mutation Research. Science Direct Electronic Journal Collection. Volume / issue 523-524 pg 87-97
Beers M.H., Berkow R. (1999) The Merck Manual 17th Edn. Merck Research Laboratories, Whitehouse Station, New Jersey
Clifton, P. M. (2004) Effect of grape seed extract and quercetin on cardiovascular and endothelial parameters in high-risk subjects. Journal of Biomedicine & Biotechnology. 5, 272–278.
Das D. K., Sato M., Ray P. S., Maulik G.. (1999) Cardioprotection of red wine: Role of polyphenolic antioxidants. Drugs Exp. Clinical. Res. 25, 115–120
Ellison S. (2006) Hidden Truth About Cholesterol-Lowering Drugs. Health Myths Exposed, LLC.
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Folts, J. D. (2002) Potential health benefits from the flavonoids in grape products on vascular disease, Adv. Exp. Med. Biol. 505, 95–111.
Ghosh D. and Scheepens A. (2009) Vascular action of polyphenols Molecular Nutrition Food Res. 2009, 53, 322 – 331
Gordon D.J., Probstfield J.L., Garrison R.J., Neaton J.D., Castelli W.P., Knoke J.D., Jacobs D.R., Bangdiwala S. and Tyroler H.A. (1989). High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation. Journal of the American Heart Association. Number 79 pages 8-15, Dallas, Texas
Hecht H.S. & Harmann SM. (2003) “Relation of aggressiveness of lipid-lowering treatment to changes in calcified plaque burden by electron beam tomography.” American Journal of Cardiology. Aug 1;92(3):334-6.
Kapur N.K., Ashen D., Blumenthal R.S. (2008). High density lipoprotien cholesterol: an evolving target of therapy in the management of cardiovascular disease. Vascular Health and Risk Management 4(1) pages 39-57. Dove Medical Press Limited
Kar P., Laight D., Rooprai H.K., Shaw K.M. and Cummings M. (2009) Effects of grape seed extract in Type-2 diabetic subjects at high cardiovascular risk: A double blind randomized placebo controlled trial examining metabolic markers, vascular tone, inflammation,
oxidative stress and insulin sensitivity. Diabetic Medicine "Accepted Article 26th March 2009”; doi: 10.1111/j.1464-5491.2009.02727.x
Langsjoen P. H. & Langsjoen A. M.(2003) The clinical use of HMG Co-A reductase inhibitors (statins) and the associated depletion of the essential co-factor coenzyme Q10: a review of pertinent human and animal data. Biofactors. 2003;18(1-4):101-11 Oxford, England.
Lichtenstein A.H., Lawrence J.A., Brands M., Carnethon M., Daniels S., Franch H.A, Franklin B., Kris-Etherton P., Harris W.S., Howard B., Karanja N., Lefevre M., Rudel L., Sacks F., Horn L.V., Winston M. and Wylie-Rosett J. (2006). Diet and Lifestyle Recommendations Revision 2006: A Scientific Statement from the American Heart Association Nutrition Committee. Circulation. Journal of the American Heart Association. Number 114 pages 82-96, Dallas, Texas
McPhee S.J., Papadakis M.A. (2009) 2009 Current Medical Treatment & Diagnosis. McGraw Hill Medical, New York
Ministry of Public Health (2007) Public Health Statistics A.D. 2006. Bangkok, Thailand
Nassir-Asi M. & Hosseinzadch H. (2009) Review of the Pharmacological Effects of Vitis
vinifera (Grape) and its Bioactive Compounds. Phytotherapy Research Published online in Wiley Interscience (www.interscience.wiley.com) DOI: 10.1002/ptr.2761
Newman T. B. & Hulley S. B. (1996) Carcinogenicity of lipid lowering drugs. Journal of the American Medical Association Jan 3;275(1):55-60
Nuttall S.L., Kendall M.J., Bombardelli E. and Morazzoni (1998) An evaluation of the antioxidant activity of a standardized grape seed extract, Leucoselect. Journal of Clinical Pharmacy and Therapeutics (1998) 23, 385–389
Pagana K. D. & Pagana T. J. (2009) Mosby’s Diagnostic and Laboratory Test Reference 9th Edn. Mosby Elsevier, China
Preuss, H. G., Wallerstedt, D., Talpur, N., Tutuncuoglu, S. O., Echard B., Myers A., Bui M. and Bagchi D. (2000) Effects of niacin-bound chromium and grape seed proanthocyanidin extract on the lipid profile of hypercholesterolemic subjects: A pilot study. Journal of Medicine. 31, 227–46
Rassmussen S.E., Frederlksen H., Krogholm K.S. and Poulsen L. (2005) Dietary proanthocyanidins: Occurrence, dietary intake, bioavailability, and protection against
cardiovascular disease. Molecular Nutrition Food Res. 49, 159 – 174
Ray S., Bagchi D., Lim P.M., Bagchi M., Gross S.M., Kothari S.C., Preuss H.G. and Stohs S.J. (2001) Acute and longterm safety evaluation of a novel IH636 grape seed pranthocyanidin extract. Resource Community of Molecular Pathology and Pharmacology. Mar-Apr;109(3-4):165-97
Tatley M. & Savage R. (2007) Psychiatric adverse reactions with statins, fibrates and ezetimibe: implications for the use of lipid-lowering agents. Drug Safety 30(3):195-201
Tuteja S., Pyrsopoulos N. T., Wolowich W. R., Khanmoradi K., Levi D. M., Selvaggi G., Weisbaum G., Tzakis A. G. and Schiff E. R. (2008) Simvastatin-ezetimibe-induced hepatic failure necessitating liver transplantation. Pharmacotherapy. Sep;28(9):1188-93.
Ursini F. & Sevanian A. (2002) Wine polyphenols and optimal nutrition. Annals of the New York Academy of Sciences. May;957:200-9.
Vinson, J. A., Proch, J., Bose, P., (2001) Mega natural gold grapeseed extract: In vitro antioxidant and in vivo human supplementation studies, Journal of . Medicinal Food 4, 17–26.
Walsh, J.M. & Pignone, M. (2004) Drug Treatment of hyperlipidemia in women. Journal of the American Medical Association. May 12;291(18):2243-52
Wren A.F., Cleary M., Frantz C., Melton S. and Norris L. (2002) 90-day oral toxicity of a grape seed extract (IH636) in rats. Jounal of Agricultural Food Chemistry. Mar27;50(7):2180-92
Yamakoshi J., Saito M., Kataoka S. and Kikuchi M. (2002) Safety evaluation of proanthocyanidin rich extract of grape seeds. Food and Chemical Toxicology. May; 40(5):599-607
Following is a review on the clinical use of grape seed antioxidant I prepared last year (THOSE THAT ARE NOT INTERESTED DO NOT READ, this was an academic presentation so is a little technical but not overly so). Further, this information is intended for just general consideration as, this for that cook-book medicine is very low class compared to a developed understanding of an individual's unique biological predicament.
Reflective Practice Exercise: The clinical prescription of Grape Seed Extract for individuals with high cholesterol and unfavourable cardiovascular risk ratios.
Critical Analysis: The practice of employing 12000-24000 mgs. per day of whole Grape Seed Extract (GSE) manufactured by Hilda Hemme Herbals or Blackmores to specifically lower cholesterol and raise high-density lipoprotein (HDL) relative to low-density lipoprotein (LDL) is of considerable importance within my clinical practice upon reflection of my clinical actions and strategies due to:
1. The frequency of high cholesterol (HC) with unfavourable HDL levels and LDL ratios within my new patient pool.
2. Often recommending GSE to replace medically prescribed statins for HC based on assumption of the safety and effectiveness of GSE relative to statins.
3. Contemporary medical belief and practice based on accepting life-threatening consequences of high cholesterol, and afflicted patients' anxiety over their perceived risk of life-threatening cardiovascular events.
4. Personal anxieties related to using GSE for HC and its’ actual benefits and potential risks to my patients, practice and profession. These anxieties principally arise from my current approach relying on information from many sources, including some no longer available, combined with seemingly good clinical results accepted without critical review. Specifically, I assume GSE is safe except for people with grape allergy, is effective in lowering cholesterol, relatively raises HDL and lowers LDL and that statins based drugs have considerable associated iatrogenic dangers.
The foregoing GSE and HC management issues and concerns, highlighted by reflective practice, suggest the need to acquire a contemporary understanding of these issues by identifying and critically examining literature relevant to:
1. The biological plausibility, clinical justification and optimal dosage/s and form/s of GSE for HC and cardiovascular disease.
2. The clinical effectiveness of GSE and its relationship to the clinical effectiveness of statins for HC and cardiovascular disease.
3. Potential benefits, dangers or risks associated with the clinical use of GSE and statins.
4. The relationship of HC to cardiovascular events.
Synthesis: Examination of the preceding analysis reveals the utility of the proposed investigation is primarily dependent on an established relationship between cardiovascular disease/s and high cholesterol and the details of this relationship if present. Cardiovascular risk factors other than those directly related to VLDL, LDL and HDL cholesterol while personally acknowledged will not be considered within this document. Similarly, discussion about the polypeptide Apo(A) fractions of HDL, Apo(B) fractions of LDL and the plasminogen-like lipoprotein Lp(A) composed of apo(A) and apo(B)100 that is strongly associated with cardiovascular disease and resistant to most cholesterol lowering medicines except Niacin will not be specifically detailed (Pagana 2008 pg 106-108).
Cholesterol and Cardiovascular Disease: Contemporary medicine accepts a pathologic role of elevated cholesterol in the genesis of arteriosclerosis and coronary artery disease in which, elevated LDL and very low-density lipoprotein (VLDL) penetrate the arterial wall by oxidative processes. Oxidised LDL and VLDL are cytotoxic to endothelial cells and chemotactic to monocytes which promote their migration into the intima and sub-intimal compartment of arteries and the accumulation of lipids in foam and smooth muscle cells. Trapped foam cells die with an oxidative burst while lipid laden smooth muscle cells become hyperplastic and may bulge into the lumen exposing the sub-endothelium to platelet aggregation, mural thrombi formation and promote arteriosclerotic plaque. These plaques can progress to frank arterial stenosis or occlusion and become stable by calcifying or spontaneously rupture and cause coronary artery disease (CAD) or acute ischemic events, including life-threatening myocardial infarction, cerebral vascular accidents and pulmonary embolisms. (Beers & Berkow 1999 pg1655-6)
Total cholesterol equals VLDL plus LDL plus HDL. As most cholesterol is LDL high serum cholesterol is associated with CAD. Many laboratories only report total cholesterol, triglycerides and HDL. These measures allow calculation of VLDL by dividing triglycerides by five if <400, and LDL by subtracting HDL and the calculated VLDL value from total cholesterol. Elevated LDL and VLDL cholesterol levels are directly related to CAD whereas elevated HDL is inversely related regardless of sex, age and ethnicity. Understanding lipoprotein fractions within total cholesterol provides a more accurate assessment of a patient's coronary risk than consideration of total cholesterol. (McPhee & Papadakis 2009 pg 1095-6)
There are 5 classes of HDL 2a, 2b, 3a, 3b and 3c, only 2b is capable of reverse cholesterol transport and cardio-protection. HDL <40mg/dl is associated with low 2b, 40-60 minimal 2b and if >60 2b tends to dominate the HDL profile, 2b can be increased by cholesterol lowering Niacin but not statins. LDL has 7 classes, from the largest to the smallest; 1, 2a, 2b, 3a, 3b, 4a and 4b. The most commonly elevated LDL’s are 3a and 3b which are small enough to penetrate endothelial cells and promote atherosclerotic disease. LDL4 is especially dangerous, if >10% of total LDL nearly all patients have vascular events within months. VLDL is reported less arteriosclerotic than LDL, but can be converted to LDL within muscle cells, VLDL >25% of total cholesterol is a cardiovascular risk factor. The cardiovascular risk ratio, total cholesterol to HDL, ideally should be 3 and if >5 indicates increased cardiovascular risk. (Pagana 2009 pg 598-600)
Lowering cholesterol reduces cardiovascular mortality and events in patients with known arteriosclerosis but not in patients without arteriosclerotic disease (Beers & Berkow 1999 pg 1656: McPhee & Papadakis 2009 pg 1096-9). Recent Thai public health statistics report cardiovascular related deaths to be the third leading cause of death in Thailand after cancer and poisoning plus accidents (Ministry of Public Health 2007 pg 46).
Treatment to lower cholesterol is currently recommended if there is a genetic propensity or familial history of CAD, premature arteriosclerosis, very high LDL or triglycerides, or very low HDL (McPhee & Papadakis 2009 pg 1095-6). The American Heart Association recommends total LDL below 100 mg/dl and not above 160 mg/dl, has no definite goals for HDL and triglycerides but states HDL <50 mg/dl and triglycerides >150 mg/dl are criteria for metabolic syndrome (Lichtenstein et.al 2006 pg 84). The cardiac risk ratio offers a useful index to monitor patient's risk trends but tends to overstate the protective effects of increasing HDL at low levels (McPhee & Papadakis 2009 pg 1097) and not reliable without considering other risk factors including obesity, smoking, hypertension and diabetes, as high LDL and low HDL are independent risk factors for cardiovascular disease (Gordon et.al. 1989, Kapur et.al. 2008).
The foregoing analysis is based on recent medical texts (Beers M.H., Berkow S. 1999, McPhee & Papadakis 2009), recommendations of the American Heart Association (Lichtenstein A.H., et.al 2006) and the research reviews cited (Gordon et.al.1989, Kapur et.al. 2008) and suggests there is a strong relationship between high LDL or VLDL and low HDL cholesterol with cardiovascular disease.
Cholesterol, Statin Drugs and Hypercholesterolemia: Cholesterol is essential for health and needed to synthesise; bile acids, vitamin D, steroid hormones, stabilise cell membranes, myelin and immune function (Ellison 2006). Further, cholesterol comprises >half the dry weight of the cerebral cortex and is vital to neurological function and serotonin metabolism (Fallon & Enig 2004). As stated in the preceding section, there is some evidence that lowering high cholesterol decreases cardiovascular events or mortality in arteriosclerotic patients but not in patients without arteriosclerosis. However, numerous epidemiological studies report increased mortality associated with low or lowering cholesterol (Ellison 2006, pg 5-7). The apparent disparity between decreased cardiovascular events or mortality and increased mortality appears to arise from reporting different measures and study populations.
Studies reporting decreased cardiovascular events or mortality usually report relative rather than absolute risk while those reporting increased mortality report total mortality a much stronger measure of actual effect (Ellison 2006 pg 5-8, 10, 12,13). Similarly, studies finding decreased cardiovascular mortality associated with low or lowering cholesterol tend to suffer age and gender biases by reporting study populations composed of nearly exclusively middle aged males (Ellison 2006 pg 8,9: Walsh & Pignone 2004). Whereas the numerous studies finding increased mortality associated with low or lowering cholesterol cited by Ellison (Ellison 2006 pg 5-7) suffer age and selection biases by reporting elderly or disease specific populations. Collectively, the foregoing suggests that the preventative role of statin drugs for cardiovascular mortality is poorly supported by research except for middle aged males with known arteriosclerotic disease and that statins appear hazardous for the elderly.
Despite statins reliably lowering cholesterol they do not prevent early death from heart disease, heart attack or stroke (Ellison 2006 pg 13) or slow arteriosclerotic plaque formation (Hecht & Harman 2003). Statin drugs lower cholesterol by inhibiting HMG-CoA reductase, this enzyme is involved in both the formation of cholesterol and substances involved in important biochemical functions including Ubiquinone (CoQ10), squalene and dilochols. The heart requires high levels of CoQ10 which has a critical role in energy supply via ATP production and cell respiration, nerve conduction, muscle membrane integrity, collagen and elastin formation (Fallon & Enig 2004). Dilochols are very important as they organise DNA synthesised proteins and cellular responses, while squalene demonstrates anti-cancer effects (Fallon & Enig 2004).
Statin's most common side effects are muscle pain, weakness and wasting or rhabdomyolysis precipitated by CoQ10 depletion (Fallon & Enig 2004). Heart failure deaths in the United States of America >doubled between 1989 and 1997 after statins were introduced in 1987. 2/3 of 20 patients with normal hearts given 20mg of Lipitor developed abnormalities in cardiac filling within 6 months and 8 of 9 other human studies investigating statin induced CoQ10 depletion found depletion with left ventricular function declines and other cardiac abnormalities (Langsjoen 2003). Neuropathic dysfunctions including polyneuropathy related weakness, tingling sensation, balance and walking difficulty are common in those taking statins for more than 1 year and often irreversible (Fallon & Enig 2004). Psychomotor, cognitive and memory impairments are also common in those taking statins (Tatley & Savage 2007) and reported in several statin studies (Fallon & Enig 2004). Statin related carcinogenesis is found in all rodent studies to date at dosages comparable to human exposures, but human studies are inconclusive due to a lack of follow-up investigations with most human cancers developing over long time frames (Newman & Hulley 1996). Lung cancer takes decades to develop even in heavy smokers, despite this several controlled statin trials do report increased rates of cancer in the statin samples (Ellison 2006 pg 19). Statin induced hepatic failure and hepatitis is not uncommon especially in the elderly (Tuteja et.al 2008). Several other statin related side-effects appear wrongly reported (Fallon & Enig 2004: Ellison 2006) including depression, suicide, immune compromise and premature death as investigation of the source materials cited and or related searches finds these events appear more linked to low cholesterol rather than directly related to statin drugs.
The findings reported in this section are primarily based on two sources (Fallon & Enig 2004: Ellison 2006) both of which exhibit strong bias against statin drugs and at times were found to misreport their supporting literature. However, the aspects reported here are believed valid after reviewing their sources or performing and reviewing database searches for related information. In summary, statin drugs' cholesterol lowering properties are undisputed similar to their inhibiting effects on CoQ10, squalene and dilochol metabolisms. Statin's primary and secondary effects have experimental, epidemiological and biological plausibility to precipitate dangerous side-effects including heart failure, multi-faceted neurological dysfunctions, cancer and liver failure. Increased surveillance for the occurrence or exacerbation of these conditions appears warranted in patients taking statin drugs as does CoQ10 supplementation.
Grape Seed Extract, Hypercholesterolemia and Cardiovascular Disease: Epidemiological studies show much less CAD despite otherwise similar risk factor profiles in those who consume red wine or the polyphenolic flavonoids resveratrol from grapes or proanthocyanidins from grape seeds (Das et.al. 1999). Grape seeds are one of the best known sources of polyphenolic flavonoids (Ghosh & Scheepens 2009) which improve endothelial function, inhibit platelet aggregation and increase LDL oxidation protection in humans (Folts 2002). Wine taken with food reduced postprandial rises in lipid hydropreoxidases and LDL oxidation, GSE proanthocyanidins appear to have the greatest antioxidant effect(Rasmussen et.al. 2005) due to being more specific for peroxyl radicals and ph independent, active within the digestive tract, and inhibit postprandial rises in plasma oxidants as well as lipid deposition (Ursini & Sevanian 2002). GSE compared to grapes, grape juice and red wine shows a greater dose-dependent inhibition LDL oxidation in vitro, in vivo 300mg of GSE was much more effective than 200mg in increasing antioxidant activity (Vinson et.al. 2001). 600mg of GSE is equal to 300ml of red wine or 1250mg of vitamin C in plasma antioxidant activity at 1 and 2 hours after ingestion and significantly increased plasma antioxidant activity with long-term supplementation and reduced total cholesterol, LDL and HDL in subjects with HC but not subjects in normal plasma lipids (Vinson et.al. 2001). 300mg of GSE showed significant increases in total antioxidant capacity in 20 subjects on standardised diets/lifestyle 30 and 60 minutes post ingestion twice daily from the first to the last day, day 5 (Nuttall et.al. 1998).
A randomised double blind placebo controlled study investigating 200mg GSE or 200mcg chromium polynicotinate or both per day found reduced total cholesterol principally from LDL reduction in the GSE -2.5%, chromium -10% and combination -16.5% groups with no significant change in HDL and triglycerides between the groups over a 2 month period. The combination group showed a 20% drop in LDL. Further, 60% of the group receiving GSE showed a >50% reduction of autoantibodies to oxidised LDL compared to only10% in the chromium polynicotinate group (Preuss et.al 2000: Bagchi et.al. 2003). Similarly, 600mg of GSE in a placebo controlled randomised blinded crossover design study of 32 type 2 diabetics over 4 weeks found decreased total cholesterol p=0.05 with insignificant changes in HDL and triglycerides (Kar 2009). These studies consistently suggest that GSE raises the ratio of HDL to total cholesterol by virtue of lowering LDL.
The improved lipid profile effects of GSE have also been demonstrated in many rat and rabbit studies that additionally report a very strong anti-arteriosclerotic effect and other cardio protective actions including decreased platelet aggregation, improved endothelial function and eNOS (Nassiri-Asi & Hosseinzadch 2009: Bagchi et.al 2003 ). However, Clifton reported no significant changes in lipid profiles in a double blinded randomised crossover of control and active ingredient/s study testing 2gms of GSE in yoghurt per day during a 12 week period but did find increased flow mediated dilation in the GSE groups. Clifton's combining GSE with yoghurt, lack of medication and alcohol consumption exclusion criteria, poorly designed diet, and employing several previously undocumented measures suggest caution in accepting his findings in regard to the clinical use of GSE (Clifton 2004).
GSE is proanthocyanidins rich and more importantly they occur in readily absorbable forms including catechin monomers, proanthocyanidin dimers and simple phenolic compounds. Proanthocyanidins appears the most important substances in grapes for cardio protection but a synergistic response from other constituents cannot be excluded. Human inability to digest and metabolise polymeric proanthocyanidins explains why GSE's in vitro responses are often reproducible in vivo unlike the polymeric forms unless injected intravenously that appear more effective in vitro (Ramussen et.al. 2005).
Proanthocyanidins are anti-inflammatory and inhibit monocyte adhesion involved in arteriosclerosis, in vivo, only the monomer and dimer forms are relevant and this effect has been demonstrated in several recent human studies (Ramussen et.al. 2005) in contrast to Clifton's (Clifton 2004) hsCRP, TNF-a, VCAM-1 and ICAM-1 findings. Red wine and grape polyphenols have convincingly shown beneficial vasodilator effects in humans by increasing intracellular Ca activating eNOS, but in vitro results do not find monomer and dimer proanthocyanidins effective only trimers and larger, thus the agent involved maybe a metabolic by-product that has still not been identified. Platelet derived growth factor (PDGF) is a potent mitogenic and chemotactic agent involved in all stages of arteriosclerosis that is inhibited by red but not white wine polyphenols, however enriching white wine with GSE to mimic the mash fermentation of red wine inhibits PDGF suggesting the mash fermentation of red wine releases active compounds from grape seeds.(Ramussen et.al. 2005)
Database searches for iatrogenic, side effects and toxicity with grape seed extract searched on PubMed, US FDA and Australian TGA found no references to noxious effects from GSE. Similar to several animal studies (Yamakoshi et.al. 2002: Wren et.al. 2002: Ray et.al. 2001). Further, I contacted Hilda Hemme the manufacturer of my preferred GSE supplement who confirmed a lack of known toxicity and informed of recent TGA labelling changes wherein GSE 12,000mg capsules can now be labelled 2 per day for the general public.
Summary of Grape Seed Extract Findings: Despite relatively few human trials on GSE it does have an established role in the management of human HC wherein it appears to selectively lower LDL the most undesirable fraction of total cholesterol while maintaining HDL and VLDL. This obviously improves the cardiovascular risk ratio and GSE also has established benefits to endothelial function, platelet aggregation, inflammatory monocyte adhesion and oxidation of LDL. Epidemiological and clinical research research suggests that whole GSE is the most beneficial form despite in vitro findings suggesting poorly absorbed polymeric proanthocyanidins are more efficient. Further, the lack of societal experience and regulatory body findings of toxicity, and the dose responsive nature of GSE effects suggests higher doses in keeping with the current TGA labelling recommendations will be more beneficial than lower doses reported.
Evaluation: This reflective exercise clarified my understanding of cholesterol related cardiovascular disease and specific types of cholesterol's benefits and risks. High LDL and VLDL or low HDL is clearly involved with CAD and life threatening cardiovascular conditions. However, statins's risks appear greater than their benefits for most people and despite GSE not being found in this review to lower total cholesterol as much as statins it has a more selective action against the most harmful fraction LDL and many other cardiovascular and health benefits unlike statins. The dose dependent nature of GSE effects do not rule out the possibility of cholesterol lowering results comparable to statins at the dosage I currently use.
The findings of this exercise largely support my current actions but will allow greater precision in my future management of HC and enhance my ability to provide factual information to patients and decrease anxieties related to HC clinical management. Further, a much wider array of knowledge than described here was gained by performing this exercise that may also improve my clinical efficiency or warrant specific investigation/s.
Conclusion: Reflective practice identified my greatest clinical management concern and helped resolve related issues by addressing my most pertinent professional development needs. Specifically it enhanced my ability to provide better care and interact with other healthcare providers, patients and regulatory bodies in an evidence based format. Further, other issues were identified that will benefit from specific investigation. Reflective practice appears the most efficient and valuable professional development tool available to practitioners by clarifying and accommodating their actual clinical needs.
List of References
Bagchi D., Sen C.K., Ray S.D., Das D.K., Bagchi M., Preuss H.G. and Vinson J.A. (2003) Molecular mechanisms of cardioprotection by a novel grape seed proanthocyanidin extract. Fundamental and molecular mechanisms of mutagenesis: Mutation Research. Science Direct Electronic Journal Collection. Volume / issue 523-524 pg 87-97
Beers M.H., Berkow R. (1999) The Merck Manual 17th Edn. Merck Research Laboratories, Whitehouse Station, New Jersey
Clifton, P. M. (2004) Effect of grape seed extract and quercetin on cardiovascular and endothelial parameters in high-risk subjects. Journal of Biomedicine & Biotechnology. 5, 272–278.
Das D. K., Sato M., Ray P. S., Maulik G.. (1999) Cardioprotection of red wine: Role of polyphenolic antioxidants. Drugs Exp. Clinical. Res. 25, 115–120
Ellison S. (2006) Hidden Truth About Cholesterol-Lowering Drugs. Health Myths Exposed, LLC.
Fallon S. & Enig M. G. (2004) Dangers of Statin Drugs: What You Haven’t Been Told About Popular Cholesterol-Lowering Medicines. Wise Traditions. Weston A. Price Foundation. http://www.westonaprice.org/moderndiseases/statin.html viewed on 1st May 2009
Folts, J. D. (2002) Potential health benefits from the flavonoids in grape products on vascular disease, Adv. Exp. Med. Biol. 505, 95–111.
Ghosh D. and Scheepens A. (2009) Vascular action of polyphenols Molecular Nutrition Food Res. 2009, 53, 322 – 331
Gordon D.J., Probstfield J.L., Garrison R.J., Neaton J.D., Castelli W.P., Knoke J.D., Jacobs D.R., Bangdiwala S. and Tyroler H.A. (1989). High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation. Journal of the American Heart Association. Number 79 pages 8-15, Dallas, Texas
Hecht H.S. & Harmann SM. (2003) “Relation of aggressiveness of lipid-lowering treatment to changes in calcified plaque burden by electron beam tomography.” American Journal of Cardiology. Aug 1;92(3):334-6.
Kapur N.K., Ashen D., Blumenthal R.S. (2008). High density lipoprotien cholesterol: an evolving target of therapy in the management of cardiovascular disease. Vascular Health and Risk Management 4(1) pages 39-57. Dove Medical Press Limited
Kar P., Laight D., Rooprai H.K., Shaw K.M. and Cummings M. (2009) Effects of grape seed extract in Type-2 diabetic subjects at high cardiovascular risk: A double blind randomized placebo controlled trial examining metabolic markers, vascular tone, inflammation,
oxidative stress and insulin sensitivity. Diabetic Medicine "Accepted Article 26th March 2009”; doi: 10.1111/j.1464-5491.2009.02727.x
Langsjoen P. H. & Langsjoen A. M.(2003) The clinical use of HMG Co-A reductase inhibitors (statins) and the associated depletion of the essential co-factor coenzyme Q10: a review of pertinent human and animal data. Biofactors. 2003;18(1-4):101-11 Oxford, England.
Lichtenstein A.H., Lawrence J.A., Brands M., Carnethon M., Daniels S., Franch H.A, Franklin B., Kris-Etherton P., Harris W.S., Howard B., Karanja N., Lefevre M., Rudel L., Sacks F., Horn L.V., Winston M. and Wylie-Rosett J. (2006). Diet and Lifestyle Recommendations Revision 2006: A Scientific Statement from the American Heart Association Nutrition Committee. Circulation. Journal of the American Heart Association. Number 114 pages 82-96, Dallas, Texas
McPhee S.J., Papadakis M.A. (2009) 2009 Current Medical Treatment & Diagnosis. McGraw Hill Medical, New York
Ministry of Public Health (2007) Public Health Statistics A.D. 2006. Bangkok, Thailand
Nassir-Asi M. & Hosseinzadch H. (2009) Review of the Pharmacological Effects of Vitis
vinifera (Grape) and its Bioactive Compounds. Phytotherapy Research Published online in Wiley Interscience (www.interscience.wiley.com) DOI: 10.1002/ptr.2761
Newman T. B. & Hulley S. B. (1996) Carcinogenicity of lipid lowering drugs. Journal of the American Medical Association Jan 3;275(1):55-60
Nuttall S.L., Kendall M.J., Bombardelli E. and Morazzoni (1998) An evaluation of the antioxidant activity of a standardized grape seed extract, Leucoselect. Journal of Clinical Pharmacy and Therapeutics (1998) 23, 385–389
Pagana K. D. & Pagana T. J. (2009) Mosby’s Diagnostic and Laboratory Test Reference 9th Edn. Mosby Elsevier, China
Preuss, H. G., Wallerstedt, D., Talpur, N., Tutuncuoglu, S. O., Echard B., Myers A., Bui M. and Bagchi D. (2000) Effects of niacin-bound chromium and grape seed proanthocyanidin extract on the lipid profile of hypercholesterolemic subjects: A pilot study. Journal of Medicine. 31, 227–46
Rassmussen S.E., Frederlksen H., Krogholm K.S. and Poulsen L. (2005) Dietary proanthocyanidins: Occurrence, dietary intake, bioavailability, and protection against
cardiovascular disease. Molecular Nutrition Food Res. 49, 159 – 174
Ray S., Bagchi D., Lim P.M., Bagchi M., Gross S.M., Kothari S.C., Preuss H.G. and Stohs S.J. (2001) Acute and longterm safety evaluation of a novel IH636 grape seed pranthocyanidin extract. Resource Community of Molecular Pathology and Pharmacology. Mar-Apr;109(3-4):165-97
Tatley M. & Savage R. (2007) Psychiatric adverse reactions with statins, fibrates and ezetimibe: implications for the use of lipid-lowering agents. Drug Safety 30(3):195-201
Tuteja S., Pyrsopoulos N. T., Wolowich W. R., Khanmoradi K., Levi D. M., Selvaggi G., Weisbaum G., Tzakis A. G. and Schiff E. R. (2008) Simvastatin-ezetimibe-induced hepatic failure necessitating liver transplantation. Pharmacotherapy. Sep;28(9):1188-93.
Ursini F. & Sevanian A. (2002) Wine polyphenols and optimal nutrition. Annals of the New York Academy of Sciences. May;957:200-9.
Vinson, J. A., Proch, J., Bose, P., (2001) Mega natural gold grapeseed extract: In vitro antioxidant and in vivo human supplementation studies, Journal of . Medicinal Food 4, 17–26.
Walsh, J.M. & Pignone, M. (2004) Drug Treatment of hyperlipidemia in women. Journal of the American Medical Association. May 12;291(18):2243-52
Wren A.F., Cleary M., Frantz C., Melton S. and Norris L. (2002) 90-day oral toxicity of a grape seed extract (IH636) in rats. Jounal of Agricultural Food Chemistry. Mar27;50(7):2180-92
Yamakoshi J., Saito M., Kataoka S. and Kikuchi M. (2002) Safety evaluation of proanthocyanidin rich extract of grape seeds. Food and Chemical Toxicology. May; 40(5):599-607
Re: New pill may cut heart failure rate
All now available at most alternative practitioners.depression, suicide, immune compromise and premature death
.Trapped foam cells die with an oxidative burst while lipid laden smooth muscle cells become hyperplastic and may bulge into the lumen exposing the sub-endothelium to platelet aggregation, mural thrombi formation and promote arteriosclerotic plaque.
I'll take the waterboarding please.
My understanding is that then the only proven benefits are being able to stay on your bike? ( does it also apply to two wheeled vehicles?).
Would plum extract give the same results?
no more dePreston
Re: New pill may cut heart failure rate
That condition is a leading cause of hospitalization and death of people in the mid 40s to late 50s. That may be a technical description of it but you could just call it 'clogged arteries' or just say that plaque builds up on the arteries then suddenly breaks off or blocks arteries.poosmate wrote:.Trapped foam cells die with an oxidative burst while lipid laden smooth muscle cells become hyperplastic and may bulge into the lumen exposing the sub-endothelium to platelet aggregation, mural thrombi formation and promote arteriosclerotic plaque.
I'll take the waterboarding please.
This is a leading subject in cause of death here is LOS and they have some of the worst stats in the world regarding this health condition, heart hospitals here are stuffed and worked to capacity, good example are the Queen's heart hospitals, packed all the time.
Scoff if you will, but this is a informative thread to discuss alternative possibilities to commonly issued drugs which many people are now seeking. There is definitely research to back up the validity of what's being discussed here.
Resolve dissolves in alcohol
Re: New pill may cut heart failure rate
I've drank red wine nearly daily for most of my adult life... so where do I get GSE locally in the concentrated form. Because I was worried about the possible liver damage side effects, I cut my physician recommended dose of statin in half a couple of years ago.
total cholesterol before starting statin - 280
with physician recommended dose - 130
Last physical (2 months ago) after a couple of years at half the physician recommended dose:
Total cholesterol - 218
HDL - 54
LDL - 129
Triglyceride - 208
According to the above posted article - these numbers spell trouble. I recently went back to the full recommended dosage (by my U.S. physician) of the statin because of the numbers in that last physical exam.
total cholesterol before starting statin - 280
with physician recommended dose - 130
Last physical (2 months ago) after a couple of years at half the physician recommended dose:
Total cholesterol - 218
HDL - 54
LDL - 129
Triglyceride - 208
According to the above posted article - these numbers spell trouble. I recently went back to the full recommended dosage (by my U.S. physician) of the statin because of the numbers in that last physical exam.
My brain is like an Internet browser; 12 tabs are open and 5 of them are not responding, there's a GIF playing in an endless loop,... and where is that annoying music coming from?
Re: New pill may cut heart failure rate
Can you explain your 'joke' because this makes no sense in regard to the article. Thanks.poosmate wrote:All now available at most alternative practitioners.depression, suicide, immune compromise and premature death
Re: New pill may cut heart failure rate
HHF,
From my limited experience the type of extract you want to be taking is a "Standardized extract" and should say so on the bottle.
Here in Thailand the easiest one available that is a standardized extract is the one made by Blackmores, which was mentioned in Morsage's long post earlier. Should be available in Tesco/Boots/Watsons etc or most other pharmacy outlets, quite a commonly available brand here.
There may be better ones out there but you'll have to order on the net. Blackmores is an Australian comany, so it's imported and up to western standards, I think.
From my limited experience the type of extract you want to be taking is a "Standardized extract" and should say so on the bottle.
Here in Thailand the easiest one available that is a standardized extract is the one made by Blackmores, which was mentioned in Morsage's long post earlier. Should be available in Tesco/Boots/Watsons etc or most other pharmacy outlets, quite a commonly available brand here.
There may be better ones out there but you'll have to order on the net. Blackmores is an Australian comany, so it's imported and up to western standards, I think.
Resolve dissolves in alcohol
Re: New pill may cut heart failure rate
If you have drunk red wine daily in moderation for some time it is unlikely grape seed antioxidant will help but will not hurt eitherhhfarang wrote:I've drank red wine nearly daily for most of my adult life... so where do I get GSE locally in the concentrated form. Because I was worried about the possible liver damage side effects, I cut my physician recommended dose of statin in half a couple of years ago.
total cholesterol before starting statin - 280
with physician recommended dose - 130
Last physical (2 months ago) after a couple of years at half the physician recommended dose:
Total cholesterol - 218
HDL - 54
LDL - 129
Triglyceride - 208
According to the above posted article - these numbers spell trouble. I recently went back to the full recommended dosage (by my U.S. physician) of the statin because of the numbers in that last physical exam.
. Your cardiovascular risk ratio is just acceptable but raising your HDL (NIACIN?) and lowering your triglycerides (OMEGA3) seem like a prudent idea.Following is a 'little' more information about cardiovascular disease risks (less technical, patient information I prepared about 5 years ago) I am providing this info free and despite its' length it is a product of a much greater volume of pertinent critically evaluated literature. For those afflicted or at risk of cardiovascular disease the issues being discussed here are truly great concerns and vitally important to them and should be respected as such. Therefore THOSE NOT INTERESTED READ NO FURTHER, AND DO NOT COMMENT UNLESS YOU HAVE SOMETHING LEGITIMATE TO ACTUALLY CONTRIBUTE TO THIS DISCUSSION!!!
Unlike poosmate's non-humerous, self centred a**hole comments above. So you can actually contribute poosmate is 'poosmate' code for an a**hole that serves 'poo' or the bacteria that thrives on it, or are you a scat freak that still has not died of a well deserved disease?? This comment is not intended as an insult (you do a good job of that on yourself) but is a genuine inquiry based on your forum handle as; poos = shits and mate = friend in english, the language used in this forum and thereby poosmate implys shits-friend in meaning which seems a little off, but each to their own. My apologies to interested readers in advance but from past experience it would seem that poosmate would take another dump here anyway.
Cholesterol, Triglycerides and Refined Carbohydrates in Cardiovascular Disease
Between 1910 to 1980 fat consumption increased 30+% in western countries to about 150-170 gms per day, trans-fats increased from almost zero in 1911 to around 10% at present, refined vegetable fats increased from 21 to 70 gms while animal fat consumption decreased from 104 to 99 gms principally by decreased butter use and margarine use increased 900% during this time. Cholesterol consumption remained constant during these 70 years but refined sugar intake increased from about 42 kg to 60 kg per year, saturated fat intake increased 16%, oleic acid (olive oil) intake increased 33%, omega 6 oil intake increased 170% but omega 3 oil intake decreased by 87%. These fat consumption figures are not controlled for essential fatty acid content. During this time cardiovascular disease increased from about 13% to 66%, cancer from less than 4% to 24% of the population. Cholesterol cannot be the primary cause of the increased cardiovascular disease (CVD) as CVD increased 400+% while cholesterol consumption remained constant. Processed foods, trans-fats and altered vegetable oils and higher total fat intake exceeding the body’s capacity to metabolise are more likely causes of CVD from the data reported. Dysfunctional fat metabolism is also associated with most other degenerative diseases, including cancer, diabetes and fatty degeneration of the internal organs but despite this most present treatments do not address this factor.
Cardiovascular disease (CVD) affects more than 65% of the population and kills about 45% by heart attack or failure, embolisms, peripheral artery disease, kidney failure and high blood pressure. The Cholesterol theory of CVD has been based for 50 years on cholesterol being a major risk factor along with high LDL. However, the studies supporting this theory have other interpretations with more scientifically credible explanations. Cholesterol theory is supported by findings that the average cholesterol level in Americans is 220mg and at 240mg there are 400% of the average level CVD deaths and at 260mg there are 600% of average CVD level deaths. Other supporting findings come from countries where cholesterol intake averages 120 to 160 mg/dl and report CVD to be relatively rare; vegetarians are consistently found to have only 25% of the CVD in the general population and in those affected by malnutrition during the Second World War CVD decreased dramatically. The major problem with the cholesterol theory of CVD is that despite people eating cholesterol from primitive times, CVD was rare before the year 1900. Other flaws in the cholesterol theory are based on doctors having had little success with cholesterol lowering treatments that despite vast use have totally failed (not even 1%) to lower the death rate from CVD but significantly increased the rates of cancer, suicide and other illnesses in those treated. Cholesterol levels also fail to predict the onset of 40% CVD death events. Cholesterol consumption has been constant since 1900 but CVD deaths increased by 400+%. The Second World War malnutrition experience occasioned significant stress that increases endogenous cholesterol production but CVD deaths decreased. Further, increased dietary cholesterol consumption increases the cholesterol level in only 30% of population, in the rest their liver’s decreases production to compensate and in many groups who consume traditional diets that contain very high cholesterol (Eskimo and Inuit) CVD is rare.
An alternative theory of CVD is the Triglyceride (TG) and Sugar theory, which has blood level correlations as strong as cholesterol’s, TG levels increase with increased refined carbohydrate and saturated fat consumption and CVD deaths parallel the dietary shift in triglycerides and refined carbohydrates since 1900. Refined sugars increase cholesterol and hard fat production. Decreased consumption of refined carbohydrates and saturated fat is associated with increased vigour and longevity. Sugar excess raises TG level and oxidation damage, cross links proteins and can cause immune dysfunction or stress the transport system of Vit C and other antioxidants.
Another theory is the Oxidation theory of CVD, where CVD is caused by oxidised cholesterol and TGs damaging the arterial walls. This theory does explain the benefits frequently found by increased antioxidant consumption and limiting sugar that competes for antioxidant transport but does not explain the profound benefits of omega 3 fish oils that require increased antioxidant protection.
The Deficiency theory of CVD suggests that deficiency of fibre, antioxidants, essential fatty acids, vitamins and minerals are causes of degenerative diseases including CVD and is supported by improving deficiencies generally lowers TG and cholesterol levels. Dr Linus Pauling (3 Nobel prizes) suggests that vit C deficiency causes deposition of the repair proteins lipoprotein A or apo(a) and fibrinogen or fibrin in response to loss of capillary integrity, vit C is needed to form collagen and elastin to maintain the vessel walls and vit C is one of the strongest antioxidants. In a stepwise progression this theory proposes that vit C deficiency weakens the arteries and results in deposition of repair proteins that oxidised cholesterol and triglycerides adhere to leading to aggregation and decreased elastic function. The body’s reaction to vit C deficiency thus thickens the arteries, slows blood flow and narrows the blood vessels, which causes raised blood pressure that precipitates heart and kidney failure. This theory explains all current observations and known phenomena unlike the other theories presented, especially the totally redundant cholesterol theory.
Only nutritional approaches are needed to lower the cholesterol level in 499 of 500 people and the 1 in 500 with a genetic cholesterol problem still can benefit by improved nutrition. Other helpful factors are controlling your weight and avoiding refined foods, coffee, ceasing smoking that raises cholesterol and improving stress management. Lowering the levels of fats and LDL cholesterol should be done cautiously as these also carry antioxidants to our cells and the high incidence of cancer, neurodegenerative diseases and suicide associated with cholesterol lowering patent medicines. Cholesterol, TG and LDL are not key CVD risk factors they only aggravate underlying problems that generally arise from oxidised blood lipids, high transfat consumption, excesses of sugar or saturated fats, high apo(a) and fibrinogen repair proteins and other toxic substances.
Nathan Pritikin and repeated animal experiments prove that the reversal of arteriosclerosis is possible by nutritional and fatty acid modulation or other orthomolecular nutritional interventions. CVD is a condition that responds readily to nutritional and lifestyle interventions. If you are one of the 30% of the population whose cholesterol level raises when you eat land animal fat restrict your consumption and do not eat frequently, fish and seafood generally do not raise cholesterol or triglyceride levels. Appropriate exercise and antioxidants are often beneficial along with vit C at therapeutic levels as is the restriction of excess sugars and saturated fats with optimal intake of omega 3 fatty acids, fibre and mucilage. Some other nutrition related factors that can affect cholesterol metabolism are copper deficiency increases cholesterol level; chromium supplementation decreases the cholesterol level in 50% of the population; omega 6 oils decrease cholesterol slightly in some individuals but omega 3 lowers TG levels substantially in most people; zinc may prevent hard fat formation via improved insulin response; B3 lowers VLDL and a combination of B3 and chromium lowers cholesterol in 80% of people. Carnitine, lysine, proline, potassium and magnesium, vit C, CoQ10 and bioflavonoids are sometimes beneficial, orotic acid in yogurt helps blocks cholesterol production, garlic may help by lowering TG levels and platelet adhesiveness. Stress induces adrenaline, increased oxidation and increases free radical formation, chronic stress increases cholesterol production for corticosteroid adrenal hormone production. Appropriate exercise has multiple benefits on the cardiovascular system, blood profile and lowers stress hormone levels. Obviously, all of these factors are not involved in all high cholesterol individual’s unique clinical ecology and biochemical environment, but if identifiable correction of underlying biochemical and physiological imbalances is safe, effective and often occasioned with a domino health promoting effect.
In closing remember that cholesterol is not the primary CVD risk factor and is essential for your nervous, hormonal and reproductive systems. The foregoing discussion is largely based on information contained in “Fats that Heal, Fats that Kill” by Udo Erasums, Alive Books 1995 an excellent book with a credible scientific basis that is now less controversial and currently supported by most contemporary medical scientists and extensive bodies of relevant investigation findings, basic science and medical literature.
Re: New pill may cut heart failure rate
Did I disturb your private discussion? Lighten up. I am not a pupil in your school.If you do not like my humour then do not read it.DO NOT COMMENT UNLESS YOU HAVE SOMETHING LEGITIMATE TO ACTUALLY CONTRIBUTE TO THIS DISCUSSION!!!
Had to look that one up as I do not have your vast knowledge of sh*t.are you a scat freak
And I do not live in Chaam.
no more dePreston
Re: New pill may cut heart failure rate
Another frightening and confusing read (for me at least):
http://www.second-opinions.co.uk/statins-scam.html
Now I don't know whether to stop taking Zocor (simvastatin), lower the dose, or continue with it as prescribed.
http://www.second-opinions.co.uk/statins-scam.html
Now I don't know whether to stop taking Zocor (simvastatin), lower the dose, or continue with it as prescribed.
My brain is like an Internet browser; 12 tabs are open and 5 of them are not responding, there's a GIF playing in an endless loop,... and where is that annoying music coming from?