Cholesterol is Your Friend, Not Your Enemy

Dear readers,
Check this comments by Dr.Mercola who is an osteopathic physician with vast experience in finding long-term solutions for patients who suffer from chronic illnesses using natural medicines.

Dr. Mercola, the New York Times best-selling author, has helped countless people to reach their health and weight loss goals. An osteopathic physician, board certified in family medicine, Dr. Mercola is passionate about empowering people to take control of their health using solely natural means.

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If you decide to take cholesterol-lowering drugs instead of addressing the underlying problem, you are not only stopping your body’s natural healing process, you are exposing yourself to drugs that are loaded with side effects -- not the least of which is depleting your body of Coenzyme Q10, which leads to fatigue, muscle weakness, soreness and ultimately heart failure.

DR.MERCOLA'S COMMENT :

When I first started practicing in the mid-80s, after finishing my residency program, I was already very interested in preventive medicine and checked cholesterol levels on nearly every patient I saw. A large number of people, I found, had elevated levels of cholesterol. But surprisingly, a fair number of them took their results back to their previous doctors (since I was the new kid on the block, no doubt) who reassured them their levels were normal.

Well, the problem was that the ranges of “normal” were, and still are, very misleading as they are a measure of what’s average -- based on mostly sick people.

It’s important to realize that there’s a big difference between average and healthy cholesterol levels. It’s very similar to what we’re now seeing with vitamin D levels.

Today, however, with respect to cholesterol, the pendulum has shifted the opposite way with ever lower levels of cholesterol being recommended, primarily due to the significant influence of the drug industry.

Profit, Not Health, is the Driving Factor Behind Current Cholesterol Recommendations

The pharmaceutical industry quickly realized what an enormous market they could capture with cholesterol lowering drugs. And they could do this very effectively with a drug that you’d have to take for years on end, and which, for the most part, wasn’t toxic or dangerous enough to kill you quickly.

Cholesterol lowering drugs (statins) now generate profits to the tune of tens of billions of dollars a year.

They were also able to leverage their marketing efforts by selecting experts in the medical community, and appointing them to government panels that make recommendations adopted by nearly the entire medical and health community.

On the last U.S. government's National Cholesterol Education Program panel there were nine physicians, and eight of them had clear, direct ties to the drug industry. Specifically to companies that make these kinds of drugs. As a result, the panel revised the national guidelines, advising those at risk for heart disease to attempt to reduce their LDL (bad) cholesterol to very, very low, levels.

Before 2004, a 130 LDL cholesterol level was considered healthy. The updated guidelines, however, recommended levels of less than 100, or even less than 70 for patients at very high risk.

In order to achieve these outrageous and dangerously low targets, you typically need to take multiple cholesterol-lowering drugs. So the guidelines instantly increased the market for these dangerous drugs.

Please understand that you have not been told the whole truth about cholesterol. Rather what you’re getting from most conventional health practitioners is little more than cleverly distorted marketing.

Cholesterol is Not the Evil Villain You’ve Been Led to Believe

Cholesterol is essential and crucial for a wide variety of vital functions in your body.

It’s an integral part of your cell membranes, and it’s also the precursor (the raw material) your body uses to make your steroid hormones – one of which is vitamin D. Your skin contains cholesterol, and when UVB rays from the sun hits your skin it converts that form of cholesterol to vitamin D3, which is then transported to your blood. Your body then further converts it into the active form of vitamin D.

But that’s not all. When your cholesterol levels go too low, a host of negative events occur in your body.

The Risks of Low Cholesterol

Cholesterol also essential for optimal brain health. It helps in the formation of your memories and is vital for neurological function. In fact, low cholesterol has been linked to a variety of neurological problems, including memory loss.

Having too little of this beneficial compound also:

• Increases your risk of depression
• Can increase your risk of suicide
• May lead to violent behavior and aggression
• Increase your risk of cancer and Parkinson’s disease

What is Too High?

Personally, I believe anything above 330 is likely too high. But another powerful way to determine if you’re at risk from abnormal cholesterol metabolism is to check your ratio of HDL, or “good” cholesterol, and your total cholesterol.

Your HDL percentage is a very potent heart disease risk factor.

Simply divide your HDL level by your cholesterol. That percentage should ideally be above 25 percent. Typically, the higher the better, as there are no known side effects of having too high good cholesterol.

If your ratio falls below 15-20 percent you are at high risk, and below 10 percent, it’s a significant indicator of risk for heart disease.

How to Safely and Effectively Treat High Cholesterol

Fortunately, there are simple, basic strategies that can help you regulate your cholesterol.

First, please realize that simply lowering your dietary cholesterol intake is not an effective primary strategy.

Why?

Because 75 percent of your cholesterol is produced by your liver, which is influenced by your insulin levels. Therefore, if you optimize your insulin levels, you will also regulate your cholesterol levels.

One of the most powerful ways you can do that is by exercising, and paying attention to the foods you eat. Foods that increase your insulin levels will also contribute to high cholesterol by making your liver produce more of it.

Here are my primary recommendations for safely lowering and regulating your cholesterol levels:

1. Get an appropriate amount of exercise.
2. Reduce, with the plan of eliminating, grains and sugars in your daily diet.
3. Eat the right foods for your nutritional type.
4. Eat a good portion of your food raw.
5. Make sure you’re getting plenty of high-quality, animal-based omega3-fats. I prefer those from krill oil.
6. Avoid excessive smoking and alcohol.
7. Address your emotional challenges.

I’ve treated between 20-30,000 patients, and I’ve only found about five people who were unable to respond to the recommendations I’ve given here. In these cases they likely had a condition called familial hypercholesterolemia.

It is extremely rare, affecting about one in 1,000 people who are on cholesterol lowering medication, but for those there may actually be some benefit to taking a statin drug.

Some have asked me about taking red rice extract, and there is some confusion on that issue. Please understand that red rice extract is also a statin drug, with the same exact mechanism of action as other statins, even though it’s available over the counter.

My Neighbor's Cholesterol Challenge Nearly Killed Him

On June 5 my old next door neighbor gave me a call and asked me if we could play tennis. We used to play regularly before I moved two years ago. He used to beat me in straight sets even though he was 70 years old, he was very good in placing the ball.

Well when we played this time it was a bit different in that he was much slower and I could easily hit balls straight past him. This time I won in straight sets. Sure he was two years older and 72 now but that could not possibly account for his decreased playing level.

After our match he explained that he was tired all the time now because his doctors put him on Zocor. Foolishly they never put him on ubiquinol This should be medical malpractice. In his case the statin drug completely devastated my neighbor's health. His energy level and quickness had been radically reduced.

Fortunately he was open to trying the ubiquinol and going on some vitamin D. I am hoping he will beat me in straight sets the next time we play.

What You Must Know if You Chose to Take Cholesterol Medication

If you chose to continue taking statin drugs, then it’s vital that you understand the mechanism of action of these drugs.

They typically work by reducing an enzyme in your liver, which not only reduces the production of cholesterol, but it also reduces the production of coenzyme Q10. When you lower the production of coQ10, you increase your risk of a variety of different health problems.

Premature aging is one primary side effect of having too little coQ10 because this essential vitamin recycles other antioxidants, such as vitamin C and E.

CoQ10 deficiency also accelerates DNA damage. Therefore, it is absolutely vital to supplement with coQ10 if you’re taking a statin drug. Unfortunately, many doctors fail to inform their patients of this fact.

If you’re over 40, I would highly recommend taking a reduced form of coenzyme Q10 called ubiquinol, because it’s far more effectively absorbed by your body.

Cholesterol is such an important issue, surrounded by so much confusion that I’m offering my Special Report on this topic FREE to all my readers. Simply click this link to download this in-depth report.

GO TO :
http://mercola.fileburst.com/PDF/Cholesterol_SpecialReport.pdf

Cholesterol Homeostasis

David E Cohen, MD, PhD
Director, Harvard-MIT Division of Health
Sciences and Technology
Associate Professor of Medicine and
Health Sciences and Technology
Harvard Medical School
Boston, MA

Introduction

Cholesterol is an essential component of cell membranes and is also the precursor of steroid hormones, bile acids, and vitamin D.¹ Cholesterol is synthesized by virtually all cells in the body but cannot be catabolized. Therefore, complex metabolic pathways involving biosynthesis, absorption, distribution, and elimination are involved in maintaining cholesterol homeostasis.²

This selective review will cover the principal metabolic pathways involved in cholesterol homeostasis.

• Cholesterol Biosynthesis
• Intestinal Elimination and Absorption
• Hepatic Regulation
• Cholesterol Production and Secretion by the Liver
• Cholesterol Uptake by the Liver
• Conclusion

Cholesterol Biosynthesis

Cholesterol is synthesized by virtually all cells in the body.³

Because of its critical role in maintaining cell membrane structure and function, cells sense and control cholesterol levels. The ratio of cholesterol to other lipids (mostly phospholipids) in the cell's plasma membrane is tightly controlled. Imbalance in these lipids can trigger the cellular synthesis of cholesterol.⁴

De novo synthesis is the major contributor to the body pool of cholesterol. Each day about 800 mg of cholesterol is synthesized, 90% of which is produced in extrahepatic tissues.^5,6

In addition to synthesis, stored cholesterol can be redistributed to the cell's plasma membrane or cells can import cholesterol from plasma low-density lipoproteins (LDL).^3,4,7

Removal of cholesterol: Excessive amounts of cholesterol can destroy cellular membrane function.² Cholesterol is returned from tissues to the liver through a pathway known as "reverse cholesterol transport."^3,5

The principal mechanism for removal of excess cholesterol from extrahepatic tissues is the efflux of cholesterol from cellular plasma membranes to high-density lipoproteins (HDL).³

HDL particles take up cholesterol, transferring some of it to other plasma lipoproteins, or HDL can deliver cholesterol directly back to the liver via specialized receptors that take it up for processing and/or elimination.³

Summary: In extrahepatic tissue, cholesterol homeostasis is maintained by a balance of de novo synthesis, use of stored cholesterol, importation of cholesterol (via LDL), and removal of excess cholesterol (via HDL).

John Dietschy, MD
Professor of Internal Medicine
Division of Digestive and Liver Diseases
University of Texas Southwestern
Medical School
Dallas, TX

Intestinal Elimination and Absorption

Diet contributes to intestinal cholesterol content and it accounts for approximately a quarter of the total. The source of most intestinal cholesterol is bile.^3,5

Cholesterol loss: While the liver secretes an average of 1200 mg/day of biliary cholesterol into the small intestine, and the average Western diet contributes another 400 mg for a total of 1600 mg/day, only about half of this cholesterol is absorbed. It should be noted that there is marked variability in absorption among individuals. The remaining cholesterol in the intestinal lumen is eliminated from the body.^3,8

Additionally, most bile acids (produced in the liver by conversion of cholesterol) are recycled to the liver, but some are eliminated by fecal excretion, which represents a source of cholesterol loss from the body amounting to about 400 mg/day. Therefore, coupled with the loss of 800 mg/day of dietary and free cholesterol in bile, the total loss of cholesterol is about 1200 mg/day.³

Absorption of cholesterol: Enterocytes within the small intestine are responsible for the packaging of absorbed cholesterol and triglycerides into Apo B–containing lipoprotein particles, chylomicrons (CM).^3,9

Chylomicrons deliver triglycerides to peripheral tissues, becoming smaller as they give up their triglycerides. The resultant particles, chylomicron "remnants" (CMR), contain remaining triglycerides and intestinally absorbed cholesterol. Nearly all of these particles are rapidly taken up by the liver, where the intestinally derived triglycerides and cholesterol are stored or packaged into other lipoproteins.^3,10,11

Summary: The intestine contributes to cholesterol homeostasis through the absorption of dietary and biliary cholesterol, which adds to the body pool, and the elimination of unabsorbed free cholesterol from bile, which depletes the body pool.

In addition, a portion of cholesterol-derived bile acids are not re-absorbed from the intestine, and this also represents a loss of cholesterol from the body.

Hepatic Regulation

The liver is the principal regulator of lipid metabolism.¹² The liver synthesizes cholesterol, packages it into lipoproteins for distribution to the tissues, receives it from intestinal lipoprotein remnants as well as from plasma lipoprotein remnants, and receives it as excess cholesterol from the tissues.⁶

The liver eliminates cholesterol^3,13 by converting it into bile acids, some of which are excreted via the intestine, and by secreting it unchanged into the bile, where about half of this cholesterol is subsequently lost by fecal elimination.³

John Dietschy, MD
Professor of Internal Medicine
Division of Digestive and Liver Diseases
University of Texas Southwestern
Medical School
Dallas, TX

Cholesterol Production and Secretion by the Liver

De novo synthesis: The liver contributes relatively little cholesterol to the total body pool, synthesizing only about 10%.^5,6

Secretion of lipoproteins: In order to ensure a continuous supply of fatty acids for delivery to muscle tissue at times when dietary triglycerides are low or nonexistent (such as during a fast), the liver assembles and secretes a triglyceride-rich Apo B–containing lipoprotein, very low-density lipoprotein (VLDL).

VLDL also contains some cholesterol, which the liver contributes from its own cholesterol pool.³

Generation of Apo B remnants: As VLDL gives up its triglyceride to the tissues, the particles become smaller and proportionally more cholesterol is contained within their cores. When about 50% of the triglyceride content of these particles has been transferred, and Apo E is acquired from HDL, the particles convert to VLDL remnants (VLDLR) and approximately half of these are taken up by receptors in the liver. Those that remain in circulation continue to give up triglyceride, and as they become smaller they convert into another remnant lipoprotein, intermediate-density lipoprotein (IDL).³

Generation of LDL: About half of these remnant IDL particles are taken up by receptors in the liver, but those that are left continue to give up triglyceride and also take on cholesterol from HDL particles via the action of cholesteryl ester transfer protein (CETP) in the process of reverse cholesterol transport. Through this process, these remnant particles eventually acquire enough cholesterol that it becomes the principal lipid contained within their cores.³

As IDL continues to give up triglycerides, and acquire more cholesterol from HDL via CETP, IDL particles transfer Apo E to HDL, eventually leaving only a single protein on their surface (Apo B-100). At this point, these particles have completed their conversion to low-density lipoproteins (LDL).³

CETP action can increase plasma LDL concentrations by assisting the remnant IDL particles in acquiring cholesterol from HDL. As detailed above, some of these IDL particles are converted into cholesterol-rich LDL particles.³

LDL is the principal cholesterol-carrying lipoprotein in circulation, accounting for 65% to 75% of total cholesterol in the plasma. If cells in the periphery need to import cholesterol, they can do so by upregulating LDL receptors that will bring these particles into the cell, releasing unesterified cholesterol from their core for use or storage. The liver can also take up LDL particles via LDL receptors.^3,14

LDL particles that are not taken up by extrahepatic cells (or cleared by the liver) remain in the plasma, where they have a half-life of 2 to 4 days—significantly longer than that of other lipoproteins such as chylomicron and VLDL remnants that have a half-life of approximately 30 minutes.³


Cholesterol Uptake by the Liver

The liver receives intestinally derived cholesterol via chylomicron remnants, and as discussed above, cholesterol is also returned to the liver via remnant lipoproteins derived from VLDL (VLDLR, IDL, and LDL). Additionally, some excess extrahepatic cholesterol is returned directly via HDL particles.³

Apo B remnants assist HDL in reverse cholesterol transport: As mentioned previously in the "Cholesterol Biosynthesis" section, HDL particles transfer some of the excess cholesterol taken up from peripheral cells to other circulating lipoproteins, specifically remnant Apo B–containing lipoproteins (VLDLR, IDL, and LDL).³

CETP facilitates the transfer of cholesteryl esters from HDL particles to these Apo B remnants, thus increasing the cholesterol concentration in the cores of these particles. In this way, the remnant Apo B lipoproteins assist in reverse cholesterol transport by carrying cholesterol acquired from HDL back to the liver.^3,13

CETP also transfers triglycerides from the Apo B remnant particles to HDL. This helps to increase size and buoyancy of the HDL particles, making them more efficiently hydrolyzed by hepatic lipase, thus facilitating the uptake of HDL by the liver. As a result, plasma HDL concentrations can fall.^13,15

Clearance of LDL: The liver expresses about 70% of the body's LDL receptors, which are upregulated if hepatic cellular concentrations of cholesterol fall. By upregulating the LDL receptors, the liver accelerates the uptake of LDL, increasing the importation of cholesterol, thus restoring hepatic cholesterol concentration while at the same time effectively clearing these lipoproteins from the plasma. Because of its ability to express so many LDL receptors, the liver is the principal remover of LDL particles from the plasma.^3,5

Summary: The liver maintains cholesterol homeostasis by synthesizing cholesterol, regulating its distribution to tissues via lipoproteins, and taking up cholesterol from intestinal lipoproteins (CMR), plasma lipoprotein remnants (VLDLR, IDL, LDL), and HDL.

Additionally, the liver is capable of eliminating cholesterol, either by converting it into bile acids or excreting it unchanged into the bile.


Conclusion

Complex metabolic pathways have evolved to maintain cholesterol homeostasis across the body.²

The principal pathways of biosynthesis, intestinal elimination and absorption, and hepatic regulation of lipoproteins act interdependently to maintain the body's cholesterol pool.

The intestine, the liver, and diet contribute to the cholesterol pool.

The intestine absorbs dietary and biliary cholesterol, but perhaps more significantly, it absorbs only about half of the cholesterol presented to it, and since some of this cholesterol was contributed from bile (recycled from the liver cholesterol pool), the intestine is a source of cholesterol loss from the body pool.

Additionally, bile acids, produced from cholesterol, also recycle between the liver and intestine, and some are eliminated by the intestine.

The liver maintains cholesterol homeostasis by synthesizing cholesterol, regulating its distribution to tissues via lipoproteins, and taking up cholesterol from intestinal lipoproteins, plasma lipoprotein remnants, and HDL.

Thus, both the liver and the intestine participate in complex, interdependent processes involved in cholesterol homeostasis.

Next Article: The Biology of Atherosclerosis: The Initiating Process »

References

1. O'Keefe JH Jr, Cordain L, Harris WH, Moe RM, Vogel R. Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal. J Am Coll Cardiol. 2004;43(11):2142-2146.
2. Weber LW, Boll M, Stampfl A. Maintaining cholesterol homeostasis: sterol regulatory element-binding proteins. World J Gastroenterol. 2004;10(21):3081-3087.
3. Cohen DE, Armstrong EJ. Pharmacology of cholesterol and lipoprotein metabolism. In: Golan DE, Tashjian AH Jr, Armstrong EJ, Armstrong AW, eds. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. 2nd ed. Philadelphia, PA: Lippincott, Williams and Wilkins; 2007:417-438.
4. Lange Y, Ye J, Steck TL. How cholesterol homeostasis is regulated by plasma membrane cholesterol in excess of phospholipids. PNAS. 2004;101(32):11664-11667.
5. Turley SD, Dietschy JM. The intestinal absorption of biliary and dietary cholesterol as a drug target for lowering the plasma cholesterol level. Prev Cardiol. 2003;6(1):29-33,64.
6. Dietschy JM. Theoretical considerations of what regulates low-density-lipoprotein and high-density-lipoprotein cholesterol. Am J Clin Nutr. 1997;65(suppl 5):1581S-1589S.
7. Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science. 1986;232(4746):34-47.
8. Burnett JR, Huff MW. Cholesterol absorption inhibitors as a therapeutic option for hypercholesterolaemia. Expert Opin Investig Drugs. 2006;15(11):1337-1351.
9. Davis HR Jr, Zhu LJ, Hoos LM, et al. Niemann-Pick C1 Like 1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis. J Biol Chem. 2004;279(32):33586-33592.
10. Mamo JC, Wheeler JR. Chylomicrons or their remnants penetrate rabbit thoracic aorta as efficiently as do smaller macromolecules, including low-density lipoprotein, high-density lipoprotein, and albumin. Coron Artery Dis. 1994;5(8):695-705.
11. Pal S, Semorine K, Watts GF, Mamo J. Identification of lipoproteins of intestinal origin in human atherosclerotic plaque. Clin Chem Lab Med. 2003;41(6):792-795.
12. Shepherd J. The role of the exogenous pathway in hypercholesterolaemia. Eur Heart J Suppl. 2001;3(suppl E):E2-E5.
13. Scapa EF, Kanno K, Cohen DE. Lipoprotein metabolism. In: Rodés J, Benhamou J-P, Blei AT, et al, eds. The Textbook of Hepatology: From Basic Science to Clinical Practice. 3rd ed. Oxford, UK: Blackwell; 2007:133-141.
14. Goldstein JL, Brown MS. Molecular medicine. The cholesterol quartet. Science. 2001;292(5520):1310-1312.
15. Jansen H, Verhoeven AJM, Sijbrands EJG. Hepatic lipase: a pro- or anti-atherogenic protein? J Lipid Res. 2002;43(9):1352-1362.

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CME on this Topic

From Medscape Internal Medicine > Staying Well With Sandra Fryhofer, MD

Rethinking Calcium: Bone Health or Heartache?

Sandra A. Fryhofer, MD

Authors and Disclosures

Posted: 10/25/2010

Sandra A. Fryhofer, MD Clinical Associate Professor of Medicine, Emory University School of Medicine, Atlanta, Georgia; Past President, American College of Physicians, Philadelphia, This issue of "Staying Well" focuses on rethinking calcium recommendations. In the past, calcium concerns have focused on bone health and on how to get enough calcium. Adequate calcium intake recommendations developed by the Food and Nutrition Board at the Institute of Medicine say that children and teens 18 years of age or younger need 1300 mg daily, and adult men and women 19 to 50 years of age need 1000 mg daily. After age 50 years, the Institute of Medicine recommends even more calcium, and daily adequate intake increases to 1200 mg.[1,2] Now, a study in BMJ raises concern that supplemental calcium may have an inadvertent adverse outcome: It could hurt your heart.[3]

Calcium and Heart Woes

In this meta-analysis of 15 randomized blinded placebo-controlled trials. Dr. Mark Bolland from the University of Auckland in New Zealand and colleagues evaluated calcium supplement use (at least 500 mg daily) in more than 12,000 patients older than 40 years of age. The findings were surprising: The pooled results linked calcium supplement intake to a significant 30% increased risk for heart attack. A tendency to increased risk for stroke and sudden death was also seen, but this result was not significant. Of note, cardiovascular outcomes were not a primary endpoint in any of the individual trials. Proposed mechanisms for the higher risk include increased blood coagulability and decreased blood vessel compliance due to calcium buildup in the arterial wall. On the basis of these findings, the authors postulate that treating 1000 people with calcium for 5 years would prevent 26 fractures but cause an additional 14 heart attacks.^[3]

This is not the first time that Dr. Bolland has studied calcium intake and cardiovascular outcomes. Two years ago, results of a randomized placebo-controlled study of 1471 postmenopausal women were published that linked calcium supplements with greater cardiovascular risk.^[4] That 2008 study by Bolland and colleagues was included in their 2010 meta-analysis.

No Trials of Calcium Plus Vitamin D Were Included

The type of calcium supplement did not seem to matter, but the current meta-analysis looked at calcium supplements alone. Researchers did not include any trials looking at calcium plus vitamin D.

An accompanying BMJ editorial questions the role of calcium in bone health in reducing fractures. It even goes so far as to say that only patients with osteoporosis who are also taking medication for it should take calcium supplements, alone or with vitamin D ,and calls for further research on calcium supplement safety and efficacy.^[5]

The Women's Health Initiative evaluation of combined calcium and vitamin D found no effect on heart attack and stroke.^[6] A recent systematic review in Annals of Internal Medicine suggests that moderate to high doses of vitamin D may reduce cardiovascular risk, whereas calcium alone had no significant effect.^[7]

Back to Basics: Incorporating Adequate Calcium Into the Diet

This study has me rethinking how I talk to patients about calcium. Use of calcium supplements may be problematic from a cardiovascular standpoint. What about dietary calcium? The verdict from previous studies is good: No increased cardiovascular risk is linked to higher intake of dietary calcium.^[3] Adequate calcium intake recommendations refer to total daily intake; it does not mean the extra amount of calcium that should be added, but that's often what happens. Incorporating dietary calcium rather than taking supplements is a better way to meet adequate calcium intake recommendations.

Calcium Content of Foods: My Favorite Lists

When talking to patients about dietary calcium, it helps to have a calcium food content list. My favorite patient-friendly list of the calcium content of selected foods is in the patient education section of the UCSF Medical Center Website.^[8] It separates the calcium content of foods into the categories dairy, vegetables, fruits, legumes, grains, nuts and seeds, fish, and other (blackstrap molasses). A list on the Harvard University Health Services Website is also handy: It is only 2 pages long and includes calorie contents.^[9] The most comprehensive list of the calcium content of foods can be found on the US Department of Agriculture's Website, but at 25 pages, it is too long to download and hand out to patients.^[10]

Dietary Calcium Intake: Start With Dairy

If the goal is to consume 1000 mg calcium daily and you take in 3 servings of dairy and soy, you're almost there. For example:^[8]

• Milk (1 cup [8 oz]): 300 mg calcium
• Plain low-fat yogurt (1 cup [8 oz]): 400 mg
• Cheese (1 oz of cheddar or mozzarella): 200 mg
• Calcium-fortified soy milk (1 cup [8 oz]) 400 mg

Dietary Calcium Intake: Beyond Dairy

Encourage patients to go beyond dairy and incorporate vegetables, fruits, legumes, grains, nuts and seeds, and fish as dietary calcium sources. (Table).

Table. Nondairy Sources of Dietary Calcium^[8]

Vegetables	Acorn squash (1 cup): 90 mg Arugula (1 cup): 125 mg Broccoli (1 cup): 180 mg Chard or okra (1 cup): 100 mg Kale, raw (1 cup ): 55 mg Spinach, cooked (1 cup): 240 mg
Fruits	Figs, dried uncooked (1 cup): 300 mg Calcium-fortified orange juice (1 cup [8 oz]): 400 mg
Nuts	Sesame seeds, whole roasted (1 oz): 280 mg Almonds (1 oz): 80 mg
Fish	Canned mackerel (3 oz): 250 mg Sardines (3 oz): 370 mg
Other	Blackstrap molasses (1 tbsp): 135 mg

Rethinking Calcium Recommendations: Balancing Benefits and Minimizing Risks

Here's how I am rethinking what I tell my patients.

1. For bone health, I will still encourage adequate calcium intake, along with vitamin D, 1000 IU. Don't forget the "D."
2. I will spend more time talking to patients about dietary sources of calcium and discourage immediately turning to a calcium supplement.
3. Calcium supplements should be used to help patients attain total recommended intake, not to augment daily intake. (I prefer calcium citrate.)
4. This new study focuses on heart risks, but don't forget about kidney stones. Unlike supplements, dietary calcium is less likely to trigger stone formation.^[11]

So, add some figs and a spoonful of almonds to your salad, and also sprinkle on some sesame seeds. This new study is another reminder that too much of a good thing may be bad for you, even calcium.

References

1. Dietary Supplement Fact Sheet, Calcium: health professional fact sheet. Available at:http://ods.od.nih.gov/factsheets/Calcium_pf.asp Accessed September 22, 2010.
2. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academies Press; 1997.
3. Bolland MJ, Avenell A, Baron J, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ. 2010; 341:c3691.
4. Bolland M, Barber P, Doughty R, et al. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ. 2008;336:262-266. Abstract
5. Cleland JG, Witte K, Steel S. Calcium supplements in people with osteoporosis. BMJ. 2010;341:c3856.
6. Hsia J, Heiss G, Allison M, et al; Women's Health Initiative Investigators. Calcium/vitamin D supplementation and cardiovascular event. Circulation. 2007;115:846-854. Abstract
7. Wang L, Manson JE, Song Y, Sesso HD. Systematic review: vitamin D and calcium supplementation in prevention of cardiovascular events. Ann Intern Med. 2010;153:315-323.
8. USCF Medical Center. Calcium content of selected foods. USCF Medical Center Website. Available at:http://www.ucsfhealth.org/adult/edu/calciumContent/index.html. Accessed September 24, 2010.
9. Harvard University Health Services. Calcium content of common foods in common portions. Harvard University Health Services website. Available at:http://huhs.harvard.edu/assets/File/OurServices/Service_Nutrition_CalciumContentOfCommonFoods.pdf. Accessed September 24, 2010.
10. USDA US Department of Agriculture. National Nutrient Database for Standard Reference, Release 20. Calcium, Ca mg Content of Selected Foods per Common Measure, sorted alphabetically. Available at:http://www.nal.usda.gov/fnic/foodcomp/Data/SR20/nutrlist/sr20a301.pdf Accessed September 24, 2010.
11. Worcester EM, Coe FL. Clinical practice: calcium kidney stones. N Engl J Med. 2010;363:954-963.

BSc (Honours) Pharmaceutical and Health Sciences

Attention to all Assistant Pharmacist of Malaysia,

University of Nothingham, Malaysia is offering a new programme for qualified candidates and pharmacy personels. Those who are keen to do a degree courses can enroll and contact the person as given below. This will be also an opportunity for those who are planing to become a Tutors at private Pharmacy Colleges and continue for further developments in career as lecturers. In governments colleges, the pharmacy board had change the qualification of tutors to Degree in Pharmacy Only. So its difficult for all Assistant Pharmacist in Malaysian governments Institution to becomes tutors unless you have a degree in pharmacy. But you may try this course and becomes a tutors, scientist, reseachers on drugs.

BSc (Honours) Pharmaceutical and Health Sciences
The Pharmaceutical and Health Sciences programme is a full-time degree studied over three years leading to the award of a BSc single honours degree. All three years of the course are taught at the University of Nottingham Malaysia Campus by our experienced academic staff in the School of Pharmacy. In addition to the staff based permanently at the Malaysia Campus you will also be taught by visiting academics from Nottingham’s UK Campus and senior representatives of the Pharmaceutical Industry in Malaysia and South East Asia. Programme structure Year One During the first year teaching will concentrate on the fundamentals of the main areas of the course which are Pharmaceutics, Pharmaceutical & Medicinal Chemistry, Physiology & Pharmacology and Microbiology. Year Two In the second year you will consolidate the main topics taught in year one and start to explore these subjects in the context of industrial pharmacy and healthcare in general. Year Three The final year builds upon the basic pharmaceutical science foundation and also sees the introduction of a selection of optional modules including some in the field of business and entrepreneurship to meet the needs of employers in the Pharmaceutical and Healthcare sectors. Crucially, a semester-long research project allows the student to develop scientific research and data analysis skills in an area of their choosing. Career opportunities Pharmaceutical scientists are central to the discovery and development of new drug entities, formulation science and the design of novel drug delivery systems and therapeutics. With their training and skills, graduates from the BSc in Pharmaceutical and Health Sciences would be well placed to pursue careers in the pharmaceutical and biotechnology industries as researchers, scientists or indeed as academics in higher education. There would also be scope for graduates to enter employment in medicines sales & marketing, scientific writing and other appointments which require a general science background. Contact Master of Pharmacy (MPharm) For further details of our undergraduate MPharm course, please contact: Dr Ting Kang Nee Tel: +603 8924 8209 Email: pharmacy.enquiries@nottingham.edu.my BSc (Honours) Pharmaceutical and Health Sciences For further details of the BSc (Honours) course, please contact: Dr Nashiru Billa Tel: +603 8924 8211 Email: pharmacy.enquiries@nottingham.edu.my BEST OF LUCK !

How to Protect Yourself from these Five Pervasive Toxins

Good day to all Readers,

I was quite busy lately and didnt have much time to post new articles. Today i received email from Dr.Mercola. This is one of the articles from the famous Dr.Mercola. Read this !

Posted By Dr. Mercola | August 25 2010

A growing body of research links five of the most commonly used chemicals in the world to a host of ailments, including cancer, sexual problems and behavioral issues. Here's what CNN suggests you can do about them:

1. BPA — Bisphenol A

   BPA is used to make lightweight, clear, heat-resistant plastic. It's also used in epoxy resins.

   A growing body of research suggests that BPA poses a potential cancer risk and may disrupt the extremely sensitive chemical signals in your body called the endocrine system.

   To avoid it, buy stainless steel bottles and glass food storage containers. Switch to fresh or frozen vegetables instead of canned. If you buy plastic, check for the number on the bottom — if there is a number 7, assume the container contains BPA unless it explicitly says otherwise.

2. Phthalates

   This family of chemicals softens plastics. Phthalates are considered endocrine disrupters. Research has also shown phthalates disrupt reproductive development. Avoid shampoos, conditioners and other personal care products that list "fragrance" as an ingredient.

3. PFOA — Perfluorooctanoic acid (also called C8)

   PFOA is used to make Teflon and other nonstick and stain- or water-repellent products. PFOA causes cancer and developmental problems. You can reduce your potential exposure by using stainless steel or cast iron cookware. If you use nonstick cookware, do not overheat it — this releases toxic gas.

4. Formaldehyde

   Formaldehyde is an ingredient in resins that act as a glue in the manufacture of pressed wood products. It is a known human carcinogen, causing cancers of the respiratory or gastrointestinal tract.

   Buying furniture free from formaldehyde eliminates much of the exposure you face from the chemical. If you have wood products containing formaldehyde, increase ventilation, reduce humidity with air conditioning or dehumidifiers and keep your home cool.

5. PBDEs — Polybrominated diphenyl ethers

   PBDEs are a group of chemicals used as flame retardants. Toxicology tests show PBDEs may damage your liver and kidneys and affect your brain and behavior. Try to find products without PBDE flame retardants and be sure to sweep up dust.

Sources:

CNN May 31, 2010

Dr. Mercola's Comments:

Thanks to the spoils of the industrial revolution, your body is now home to a growing cocktail of chemicals.

Intermingling with your red and white blood cells, your endocrine system, brain, tissues and other organs are chemicals used to make epoxy resins, non-stock cookware, flame-resistant upholstery and plastic -- clearly substances that have no business taking residence in a living, breathing creature such as yourself.

Your Body Probably Contains Over 200 Chemicals

A typical American comes in regular contact with 6,000 chemicals and an untold number of potentially toxic substances on a less frequent basis. There are about 75,000 chemicals regularly manufactured and imported by U.S. industries, so you could potentially be exposed to any number of them.

Given the vast amounts of chemicals in the environment, it's not too surprising that the CDC's Fourth National Report on Human Exposure to Environmental Chemicals found an average of 212 chemicals in Americans' blood or urine.

Likewise, an Environmental Working Group study found that blood samples from newborns contained an average of 287 toxins, including mercury, fire retardants, pesticides, and Teflon chemicals, and this is from exposures they received before birth.

When it comes to the potentially hazardous chemicals you and your family are exposed to as you go about your daily lives, it can easily feel overwhelming. There are chemicals literally everywhere, but rather than feeling burdened by the thought I encourage you instead to focus on simple steps you can take to reduce your risk.

A good starting point, as CNN as suggested above, is to focus on avoiding some of the most pervasive, and most toxic, chemicals that are virtually guaranteed to be in your home right now.

Five Top Common Chemicals to Avoid …

The five chemicals listed by CNN are definitely worthy of eliminating from your life as much as possible, and given that they are among the most widely used chemicals around, doing so will make a serious positive impact on your chemical exposure.

They gave a great summary above, but I'll touch on them again briefly here:

• BPA: BPA is one of the world's highest production-volume chemicals and is widely used in the production of plastics, canned foods and soda cans, food packaging, baby bottles and toys and more.

  The chemical can lead to heart disease, diabetes and liver problems in adults, and previous research has linked BPA to serious developmental and reproductive problems.

  You can find 10 tips to minimize your BPA exposure here.

• Phthalates: Phthalates, or "plasticizers," are a group of industrial chemicals used to make plastics like polyvinyl chloride (PVC) more flexible and resilient. They're also one of the most pervasive of the endocrine disrupters.

  These chemicals have increasingly become associated with changes in development of the male brain as well as with genital defects, metabolic abnormalities and reduced testosterone in babies and adults.

  You can help reduce your exposure by using the tips in this past article.

• PFOA: Teflon-coated cookware is the primary source of dangerous perfluorinated chemicals (PFOAs). Teflon pans quickly reach temperatures that cause the non-stick coating to begin breaking down, releasing toxins that have been linked to cancer, birth defects and thyroid disease into the air in your kitchen.

  I highly recommend you throw away this type of non-stick cookware immediately and replace it with either ceramic or glass. My personal choice is ceramic cookware, because it's very durable and easy to clean, and there's absolutely no risk of exposure to harmful chemicals.

• Formaldehyde: Formaldehyde, most commonly known as embalming fluid, serves a number of purposes in manufactured products. It is actually frequently used in fabrics to give them a variety of "easy care properties" as well as being a common component of pressed-wood products.

  Formaldehyde has been shown to cause cancer in animals, and may cause cancer in humans. Other common adverse health effects include fatigue, skin rashes, and allergic reactions. Choosing all natural materials for your clothing and furniture can help cut down on your exposure.

• PBDEs: These flame-retardant chemicals have been linked to altered thyroid levels, decreased fertility and numerous problems with development when exposure occurs in utero. PBDEs are commonly found in household items like upholstery and television and computer housings. Fortunately, several states now ban the use of PBDEs, so there is some progress toward reducing exposure.

  Another common source of PBDEs is your mattress, and since you can spend up to a third of your life in bed, this is a significant health concern. Mattress manufacturers are not required to label or disclose which chemicals their mattresses contain. Look for 100 percent wool, toxin-free mattresses.

  Another viable option is to look for a mattress that uses a Kevlar, bullet-proof type of material in lieu of chemicals for fire-proofing. Stearns and Foster uses this process for their mattresses, which is sufficient to pass fire safety standards.

What Else Can You do to Reduce Unnecessary Chemical Exposure to Your Family?

Rather than compile an endless list of what you should avoid, it's far easier to focus on what you should do to lead a healthy lifestyle with as minimal a chemical exposure as possible:

1. As much as possible, buy and eat organic produce and free-range, organic foods to reduce your exposure to pesticides and fertilizers.
2. Rather than eating conventional or farm-raised fish, which are often heavily contaminated with PCBs and mercury, supplement with a high-quality purified krill oil, or eat fish that is wild-caught and lab tested for purity.
3. Eat mostly raw, fresh foods, steering clear of processed, prepackaged foods of all kinds. This way you automatically avoid artificial food additives, including dangerous artificial sweeteners, food coloring and MSG.
4. Store your food and beverages in glass rather than plastic, and avoid using plastic wrap and canned foods (which are often lined with BPA-containing liners).
5. Have your tap water tested and, if contaminants are found, install an appropriate water filter on all your faucets (even those in your shower or bath). My personal favorite, and the one I personally use, is a high-quality reverse osmosis (RO) filter. You just need to add a few minerals back to the water, but RO reliably removes virtually every possible contaminant that could be in the water.
6. Only use natural cleaning products in your home.
7. Switch over to natural brands of toiletries such as shampoo, toothpaste, antiperspirants and cosmetics. The Environmental Working Group has a great safety guide to help you find personal care products that are free of phthalates and other potentially dangerous chemicals. I also offer one of the highest quality organic skin care lines, shampoo and conditioner, and body butter that are completely natural and safe.
8. Avoid using artificial air fresheners, dryer sheets, fabric softeners or other synthetic fragrances.
9. Replace your Teflon pots and pans with ceramic or glass cookware or a safe nonstick pan.
10. When redoing your home, look for "green," toxin-free alternatives in lieu of regular paint and vinyl floor coverings.
11. Replace your vinyl shower curtain with one made of fabric, or install a glass shower door.

It is important to make these positive and gradual steps toward decreasing your chemical risk through healthy lifestyle choices. While you make the switch to remove and reduce chemicals around your home, remember that one of the ways to significantly reduce your toxic load is to pay careful attention to what you eat.

Organically-grown, biodynamic whole foods are really the key to success here, and, as an added bonus, when you eat right, you're also optimizing your body's natural detoxification system, which can help eliminate toxins your body encounters from other sources

Advanced SystemCare Pro | Advanced Care Professional | Advanced System Clean | System Care Pro Review

Hi everyone,

Today i installed this software to my 2 notebook and PC. Its really a great software that do wonders in one click! My notebook now run faster than before ! Why not try and download now for free !

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  Turbo Boost can speed up your PC by shutting down unnecessary background processes, cleaning RAM, and intensifying processor performance.

• Enjoy That New PC Feeling Again

  Whatever version of Windows you’re running, enjoy that “good as new” speed usually only experienced on a brand new PC.

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  Fully optimizes Windows for ultimate system performance and top Internet speed by unleashing the built-in power of your system, based on how you use your PC and your network configuration. Turns your PC into a business PC, a productive workstation, an entertainment center, a game machine, or a scientific computing PC.

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  Just install it and forget it. This powerful utility works continuously, automatically and quietly in the background on your PC. You can set it as your schedule or just let it work automatically when your PC is idle.

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  1. Detects and analyzes Windows security environment. Scans and removes spyware and adware using up-to-date definition files. Prevents spyware, hackers and hijackers from installing malicious programs on your computer. Erases and updates your PC’s activity histories.

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INFO TERKINI MESYUARAT TEKNIKAL PPF MSIA BIL 01/2010

Salam Sejahtera dan Salam Satu Malaysia semua PPF!

Berikut adalah ringkasan maklumat terkini hasil dari Mesyuarat Teknikal PPF Kebangsaan Bil 01/2010 di IbuPejabat Bhg Perkhidmatan Farmasi, Petaling Jaya yang diadakan pada hari ini 15 Julai jam 8.30pg - 1.00 tgh.

1. Akta baru Farmasi - disediakan melalui penggabungan 4 akta lama serta penambahbaikan akan di satukan sebagai satu akta baru. Dalam akta baru ini turut dimasukkan profesion Pen.Peg.Farmasi dan akan dibentangkan di Parlimen pada Oktober 2010. Ini bermaksud semua PPF baik swasta dan kerajaan wajib mendaftar untuk menjalankan tugas atau "practice" profesion tersebut. Satu majlis telah di tubuhkan iaitu Majlis Farmasi (Pharmacy Council) untuk melakukan aktiviti pendaftaran tersebut dan bukan Lembaga Farmasi.

2. Norma perjawatan baru telah di sediakan mengikut aktiviti di institusi masing-masing (maklumat terperinci akan di upload kemudian) dan jika berpandukan norma baru tersebut, KKM memerlukan sebanyak 4085 PPF di Hospital dan 5681 PPF di Kesihatan (tidak termasuk BIRO) Buat masa ini kita ada sebanyak 3431 PPF di KKM (termasuk BIRO). Jumlah keperluan PPF ialah 9766 tidak termasuk PPF BIRO. (Data untuk BIRO belum diperolehi).
Projection pengeluaran PPF = 1500 setahun. (23 Kolej swasta dan KSKB).

2.1. Unjuran Keperluan PPF di Kesihatan :
Pesakit Luar + Pengurusan Stor / Pentadbiran /Kualiti
Klinik Jenis 1 = 32 PPF + 2 PPF
Klinik Jenis 2 = 26 PPF + 2 PPF
Klinik Jenis 3 = 20 PPF + 2 PPF
Klinik Jenis 4 = 12 PPF + 1 PPF
Klinik Jenis 5 = 4 PPF + 1 PPF
Klinik Jenis 6 = 3 PPF + 1 PPF

2.2. Unjuran Keperluan PPF Hospital
Outpatient & Ambulatory Pharmacy - Processing&Filling = 1PPF : 50 Rx
InPatient Care (24 hrs) - Unit Dose Med Supply = 1PPF : 50 Rx
Internal Audit - 1 PPF per 5 wards
Stock Management - 1 PPF / Substore
Pre-Packing (Supervising Activity) - 1 Hospital : 3 PPF
TPN (Preparation) - 1 PPF / 10 bags
CDR (Preparation) - 1 PPF / 6 Preparations
IV AdMixture - 1 PPF / 10 Preparations
(Bilangan PPF akan berbeza mengikut jenis Hospital - Hospital Besar, Hospital Pakar Utama, Hosp Pakar Kecil, Hospital Daerah Tanpa Pakar)

3. Klinik Methadone - PPF juga telah di masukkan dalam program ini sebagai support staff.

4. Cadangan-cadangan semasa mesyuarat :
4.1 Extended Role - peranan baru PPF di Stor Integrasi dalam skop ubatan sahaja.
4.2 Permohonan jawatan U40 di tiap JKN dan bukan saja Hosp Besar.
4.3 Permohonan jawatan U36/U38 ditiap Pej.Kesihatan Daerah.
4.4 Cadangan Pos Basik baru untuk semua PPF Kes dan Hospital - Logistic Mx & Counter Mx
4.5 Permohonan skim baru "Pharmacy Aides" menggantikan PRA
4.6 Mohon di adakan bengkel dalam sebarang penyediaan kertas kerja dan beri sedikit peruntukkan kpd Ketua Profesion PPF untuk menjalankan bengkel tersebut
4.7 Sabah mohon tambah ahli mesyuarat - Persatuan PPF Sabah (Majlis setuju 1 PPF)
4.8 Mohon kursus-kursus dan attachment di luar negara melalui BPF KKM
4.9 Mohon Klinik 1Malaysia di beri pos sekurang-kurangnya 2 PPF

Sekian buat sementara waktu. Saya akan update lagi lebih maklumat dalam artikel akan datang.

Terima kasih dan salam 1Malaysia

PERKEMBANGAN TERKINI KERJAYA PPF

Berita baik kepada semua Pen.Pegawai Farmasi Malaysia !!!

Bahagian Perkhidmatan Farmasi KKM telah membuat "Penyenaraian" semua PPF dari swasta selepas mendapat feedback dari Institusi swasta bilangan Pen.Pegawai Farmasi/Pharmacy Assistant/Dispenser/Peg.Dagang/Pharmacy Technician yang berkhidmat sekarang.

Tujuannya ialah untuk menjalankan aktiviti Pendaftaran serta memperoleh "Annual Practicing Certificate" (APC) atau Practicing Certificate (PC). Menurut Timb.Pengarah Pengurusan Farmasi KKM dalam Persidangan PPF Kebangsaan di Cam.Highland 12 Julai 2010, AKTA FARMASI baru akan di bentangkan di Parlimen pada bulan Oktober 2010.

Sekiranya Akta tersebut di luluskan, semua Pen.Pegawai Farmasi, Pembantu Farmasi / Pharmacy Assistant (Swasta), Pharmacy Technician, Dispenser adalah wajib mendaftarkan profesion mereka untuk "Practice" tugas tersebut. Kegagalan mendaftar akan mengakibatkan mereka di denda atau di dakwa.

Ini bererti profesion PPF selepas ini akan di kawal dan di lindungi. Kualiti pendidikan Diploma Farmasi juga akan di pantau supaya menepati tahap pendidikan, dan tidak semua Kolej boleh menjalankan sewenang-wenangnya program Diploma Farmasi ini.

Buat masa ini terdapat 23 Institusi Pengajian Tinggi Swasta yang menawarkan program Diploma Farmasi di seluruh Malaysia. Hanya 5 Institusi sahaja di iktiraf MQA.

Adalah di harapkan dengan kelulusan Akta baru ini akan memberikan satu wajah baru dan perkembangan profesion ke tahap yang lebih tinggi seperti yang kita impi-impikan selama ini.
Moral profesion juga secara tidak langsung akan naik dan di hormati.

Sekian, semoga semua ini menjadi kenyataan selepas Oktober ini.

1ST ASSIST. PHARMACIST TECHNICAL COMMITTEE MEETING

To all Malaysian Assist.Pharmacist,

I will be attending the 1st Assist.Pharmacist Technical Committee meeting at our HQ-Pharmacy Services Division, MOH on 15th July 2010.

If you have anything to raise regarding our profession, please email me at : pfganesh@gmail.com or you can call me also at 012-5172500.

May this meeting will be our first step towards our developments. Together we pray for it !

Ganesan
Senior Assist.Pharmacist
Taiping Health Clinic

Diclofenac: Similar CV Risk to Rofecoxib in Healthy People

Dear readers,
Its shocking to know that the drug we've been using everyday in our life has this potential. This article was taken from MEDSCAPE.COM
This article is intended for primary care clinicians, cardiologists, rheumatologists, orthopaedists, and other specialists who prescribe NSAIDs to adults.

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.
Authors and Disclosure

From Heartwire CME
Diclofenac: Similar CV Risk to Rofecoxib in Healthy People CME/CE

News Author: Lisa Nainggolan
CME Author: Charles P. Vega, MD

Authors and Disclosures

June 14, 2010 — The first study to examine the cardiovascular risk associated with nonsteroidal anti-inflammatory drugs (NSAIDs) in healthy individuals has found increased morbidity and mortality with diclofenac, rofecoxib (Vioxx, Merck), and high doses of ibuprofen [1]. Naproxen, in contrast, has a safer cardiovascular risk profile, say Dr Emil Loldrup Fosbøl and colleagues in their paper published online June 8, 2010 in Circulation: Cardiovascular Quality and Outcomes.

The increased cardiovascular morbidity and mortality seen with diclofenac, which is similar to that observed with rofecoxib--a drug that was withdrawn from the market in 2004 because of poor cardiovascular safety--is particularly concerning, Fosbøl told heartwire .

Patients and clinicians need to know that [diclofenac] increases the risk of cardiovascular adverse events.

"We've been so much focused on the newer COX-2 inhibitors, but the primary message concerns diclofenac, because there is so much evidence now that this is also a problem; it has been shown quite extensively in many reports. Diclofenac has been used for almost 50 years and is available over the counter [OTC] in many countries, which I think is irrational. This is a major public-health concern, and patients and clinicians need to know that this drug increases the risk of cardiovascular adverse events. "

Also worrying is the fact that the results were dose-dependent, and diclofenac is more often used in high doses compared with other NSAIDs, say Fosbøl and colleagues. "Our results suggest that naproxen could be a safer alternative when NSAID treatment is required," they state.

Large Study, Covering Entire Population of Denmark

The researchers used a nationwide cohort of healthy individuals over the age of 10 in Denmark, made possible by the fact that all residents have a unique personal number, which enables linkage of administrative registries on an individual level. They identified more than 2.5 million people who claimed at least one prescription for NSAIDs from 1997 to 2005; after applying selection criteria regarding comorbidity and concomitant pharmacotherapy, they included just over one million individuals in the analysis.

Ibuprofen was the only nonaspirin NSAID that could be purchased OTC in Denmark during the study period, but it was available only in low doses (200 mg) and in limited quantities, say the researchers. In addition, the system in Denmark would ensure that those requiring higher doses of ibuprofen would have financial incentive to obtain a prescription from their doctor, so OTC NSAID use is unlikely to have had a significant influence on the results, they point out.

Prescription use of the nonselective NSAID diclofenac and the selective COX-2 inhibitor rofecoxib was associated with an increased risk of cardiovascular death (odds ratio 1.91 and 1.66, respectively), with a dose-dependent increase in risk.

Our results further strengthen the association between NSAID use and cardiovascular risk by demonstrating effects on all cardiovascular outcomes.

There was a trend for an increased risk of fatal or nonfatal stroke associated with ibuprofen treatment (OR 1.29), but naproxen was not associated with increased cardiovascular risk (OR for cardiovascular death 0.84).

Although rofecoxib was withdrawn in 2004, another COX-2 inhibitor, celecoxib (Celebrex, Pfizer), is still available. But Fosbøl et al say they were unable to draw any firm conclusions about the cardiovascular safety of celecoxib in this study because the analysis is based on few events, especially at higher doses. The results of the ongoing Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen and Naproxen (PRECISION) trial should shed more light on the risks and benefits of this drug, they say.

They also showed that all NSAIDs except for celecoxib were linked to a substantial increase in risk of serious bleeding, a well-known adverse effect of NSAIDs "that needs to be kept in mind."

Dr Florian Krötz (University Hospital Munich, Germany), who has recently published a review on the risk of MI associated with diclofenac [2] but was not involved with this study, told heartwire : "Concerning diclofenac and rofecoxib, I agree with the increased risk of CV death that the authors find."

However, a "major weakness" of such observational trials is the problem of correlating doctors' certificates on causes of death with numbers of prescriptions, he says. And it is unknown whether the individuals have actually taken these drugs or whether they had cardiovascular risk factors or even any history of CV disease. "As such, I think such studies must be interpreted with great caution," Krötz commented.

Fosbøl et al acknowledge these shortcomings of their trial but note that it also has its strengths, including the size and completeness of data, covering the entire population of Denmark, and the fact that two independent and different statistical approaches were employed to examine the relationship between exposure to NSAIDs and the chosen outcomes.

First Study to Show NSAIDs Affect All Cardiovascular Outcomes

The study was also the first to look at quite specific cardiovascular end points rather than just MI or MI and overall death, says Fosbøl. No previous study has reported results on specific end points such as fatal/nonfatal stroke or coronary death combined with nonfatal MI.

"Therefore, our results further strengthen the association between NSAID use and cardiovascular risk by demonstrating effects on all cardiovascular outcomes."

Population of NSAID Initiators and Sex-, Age- and Time-Matched Controls of Non-NSAID Initiators: Hazard Ratios for Specific Causes of Death Associated With Exposure Stratified According to Daily Dosagea
Drug (mg/day) CV death Coronary death or nonfatal MI Fatal or nonfatal stroke
Ibuprofen
Any use 0.88b 1.31b 1.47b
<1200 0.79b 1.24b 1.39b
>1200 1.63b 1.94b 2.22b
Diclofenac
Any use 1.20b 1.83b 2.00b
<100 0.80 1.39b 1.33c
>100 1.46b 2.10b 2.41b
Rofecoxib
Any use 1.64b 1.84b 1.12
<25 1.60b 1.82b 1.10
>25 2.77c 2.36 1.79
Celecoxib
Any use 1.24 1.44b 1.27
<200 1.19 1.44c 1.16
>200 1.51 1.49 1.95
Naproxen
Any use 0.86 0.78 1.54b
<500 0.84 0.69c 1.55c
>500 0.92 1.22 1.48

a. Compared with no use (HR=1.00)

b. p<0.05

c. p<0.01

Fosbøl says the findings underline the fact that individual NSAIDs have different degrees of cardiovascular safety, so doctors should always make an individual assessment of cardiovascular risk and carefully consider the balance between benefit and risk before starting therapy with any NSAID.

Also, because adverse CV events observed were dose dependent, it is important that NSAIDs are prescribed at the lowest possible dose for the shortest period of time, he adds. He and his colleagues were not able to examine duration of use with regard to cardiovascular risk in this study, but will do so in a future analysis, he says.

The authors declare that they have no disclosures.

References

1. Fosbøl EL, Folke F, Jacobsen S, et al. Cause-specific CV risk associated with NSAIDs among healthy individuals. Circ Cardiovasc Qual Outcomes 2010; DOI:10.1161/CIRCOUTCOMES.109.861104. Available at: http://circoutcomes.ahajournals.org.
2. Krötz F, Struthmann L. A review on the risk of myocardial infarction associated with the NSAID diclofenac. Cardiovasc Hematol Disord Drug Targets 2010; 10:53-65. Abstract

Clinical Context

The use of the COX-2 inhibitor rofecoxib has been associated with a significant increase in the risk for cardiovascular disease, and a study by Solomon and colleagues, published in the April 22, 2008, issue of Circulation, examined whether another COX-2 inhibitor, celecoxib, was also associated with cardiovascular risk. Researchers pooled data from 6 randomized trials of celecoxib and found a significant 60% increase in the risk for a combined cardiovascular endpoint associated with the use of celecoxib. However, the 400-mg daily dose of celecoxib was not associated with a higher risk for cardiovascular disease, and the rate of cardiovascular events related to the use of celecoxib was most pronounced among patients at high baseline cardiovascular risk.

The risk for cardiovascular disease may not be limited to COX-2 inhibitors; other NSAIDs have also been implicated. The current study uses a large patient database to examine this issue.
Study Highlights

* Researchers queried patient databases in Denmark for information pertaining to events between 1997 and 2005. Specifically, researchers examined a national mortality registry and a national database of inpatient admissions. They also examined a national database of prescriptions, which offers virtually complete prescription data across Denmark.
* The study group was aged 10 years or older in 1997. The main study outcome was the relationship between NSAID use and the risks for cardiovascular outcomes, which were defined by cardiovascular death, MI, and stroke. Researchers also examined rates of bleeding associated with NSAIDs.
* The study analysis adjusted for age, sex, and calendar year.
* The study cohort consisted of 1,028,437 apparently healthy individuals with a median age of 39 years; 58% of subjects were men.
* 44.7% of study subjects had an NSAID prescription claim; 2204 individuals died during treatment with an NSAID during the study period.
* The use of diclofenac and rofecoxib were associated with a higher risk for cardiovascular death (OR, 1.91 and 1.66, respectively). There was a dose-response effect in the risk for cardiovascular death associated with these medications.
* In contrast, ibuprofen, celecoxib, and naproxen were not associated with a higher risk for cardiovascular death.
* However, the use of ibuprofen (OR, 1.52), diclofenac (1.82), and rofecoxib (1.72) increased the risk for coronary death or nonfatal MI.
* The use of ibuprofen and naproxen were associated with an elevated risk for stroke.
* Overall, naproxen was associated with the lowest cardiovascular risk for the different NSAIDs examined.
* All NSAIDs, except celecoxib, were associated with a higher risk for fatal or nonfatal major bleeding. The risk of bleeding was dose dependent.
* Slightly more than half of individuals who died during NSAID treatment died of noncardiovascular causes. However, NSAIDs were not associated with a higher risk of dying of causes other than cardiovascular causes.

Clinical Implications

* A previous study evaluating randomized trial data found a significant increase in the risk for cardiovascular disease associated with the use of celecoxib. This risk was most pronounced in higher doses and among patients with a higher baseline cardiovascular risk profile.
* The current study demonstrates that NSAIDs can increase the risk for cardiovascular disease. Rofecoxib and diclofenac were particularly associated with a higher risk for cardiovascular outcomes, whereas naproxen had a safer cardiovascular risk profile.