Monday, January 2, 2012

Niacin and Cholesterol - AIM-HIGH study analysis by Jon Barron

Heart Disease Prevention | Heart Health Newsletter

Niacin and Cholesterol

I recently commented that I could easily spend my entire life doing nothing but responding to silly studies "disproving" natural remedies. And in fact, the last three newsletters have done just that. Unfortunately, we now have to make it four in a row, as we turn to a study on niacin and cholesterol. But this one has a curious difference. Unlike virtually every other study that concludes that natural remedies are useless, this one went virtually unreported by the mainstream media. And yes, I'm sure conspiracy theorists will see some nefarious plot to damage alternative medicine in this non-reporting, but in fact, non-reporting, in this case, runs counter to that agenda. That argument would make sense if the study concluded that niacin actually prevented heart disease -- and the establishment was trying to suppress that information. But, in fact, it came to the exact opposite conclusion, that niacin did not reduce heart attacks and strokes -- so why wasn't that trumpeted from the rafters?
In truth, I think the answer is far more banal than conspiracy. I think the news services didn't pick it up because they found it boring. Just like a story about Tiger Woods would make headlines around the world, but a story about Andy Matthews (number 999 in the Official World Golf Rankings1) would not; stories about the ineffectiveness of vitamin E and A and C make the news, whereas one on niacin does not. As far as the media is concerned, when it comes to stories about vitamins, niacin is on the D-List.
But in this case, the mainstream missed a huge story. Yes, the conclusion that niacin doesn't help prevent heart attacks and strokes is correct, but that's not the real story. In truth, if you actually understand what the study is really proving, it rips the facade off one of the biggest medical rackets in the world -- one that bilks gullible consumers out of billions and billions of dollars each and every year, for almost no benefit. And yes, we're talking about statin drugs. Now that's a headline worth running!
With that in mind, let's take a look at the actual study. Then we can peak behind the curtain and see what the researchers missed.

Niacin, Cholesterol, and Heart Disease

As the study itself says, more than 18 million North Americans have coronary heart disease, and despite the use of drugs and surgical intervention, both the levels of heart disease and death remain high.2 Despite all the talk of cancer, heart disease is still a big deal -- still the leading cause of death in the US, North America, and the world. And according to the medical community, elevated levels of LDL cholesterol are a primary predictor of coronary heart disease. And also, according to the researchers, a number of trials have shown a significant reduction of 25 to 35% in the risk of cardiovascular "events" when statin therapy is used. As we will discuss a bit later, this doesn't necessarily mean what everyone thinks it means, but we'll discuss that in detail a bit later. In any event, the reason for the study was to find out if adding extended-release niacin to a statin drug regimen that was already controlling cholesterol and triglyceride levels could provide an incremental benefit. As such, this study did not include a test of the ability of niacin alone to help in this regard, but merely whether or not using niacin in combination with an already implemented statin drug routine provided any additional benefit.

The trial, known as AIM-HIGH, followed more than 3,414 patients with cardiovascular disease who had used statin drugs to lower their LDL cholesterol. They then received either a high dose (1,500-2,000 mg) of extended-release niacin (Niaspan) along with their statin drug, or a placebo along with their statin drug for 32 months, at which point the trial was stopped. While the niacin-statin combination therapy increased HDL ("good") cholesterol and lowered the amount of fat in the blood better than the use of a statin-only regimen, it didn't reduce the number of heart attacks, strokes, or hospitalizations for certain other heart problems. And, in fact, according to the study, it actually slightly increased the risk of stroke. In other words, although the addition of niacin further reduced over cholesterol levels, reduced triglycerides, and improved the HDL to LDL ratio in the subjects' blood, that didn't translate into any perceivable health benefit. Interesting, yes?
As a result, the National Institutes of Health's National Heart, Lung, and Blood Institute (NHLBI), which funded the research, stopped the study more than a year early. In an accompanying NEJM editorial, Dr. Robert Giugliano of Brigham and Women's Hospital in Boston, suggested that, based on the results, it might be time to "retire" niacin, used as a cholesterol reducer since 19553 -- even making the suggestion part of the article's title, "Niacin at 56 Years of Age -- Time for an Early Retirement?"

"Given the lack of efficacy in this trial … and the unresolved question of an increased risk of ischemic stroke, one can hardly justify the continued expenditure of $800 million per year in the United States for branded extended-release niacin."

In any event, this conclusion seems a bit premature since prior research has shown significant niacin-associated declines in the rates of death, heart attacks and strokes -- but when used differently. All this study shows is that although niacin still demonstrates an ability to improve cholesterol numbers when used as a statin adjuvant, that improvement doesn't translate into improved outcomes. But it doesn't nullify the use of niacin without statins. Nor does it make clear whether the problem lies with the niacin, the statin drugs, or the cholesterol theory of heart disease itself. We'll return to this concept a bit later.

Medical comment on the study

On the positive side, after two years of using the niacin, HDL and triglyceride levels improved markedly in the niacin group, with a 25 percent increase in good cholesterol, a 29 percent drop in triglycerides and a further decrease (beyond what the statin drugs had achieved on their own) in bad cholesterol of approximately 12 percent. By contrast, in the placebo group, there was minimal change, with a 10 percent increase in good cholesterol and an 8 percent drop in triglycerides. Based on all assumptions the medical community makes based on the cholesterol theory of heart disease, this should have produced improved outcomes in patients with heart disease. The question Dr. Giugliano should have been asking is not whether or not niacin should be retired but whether or not the cholesterol theory of heart disease should be retired. As the theory goes, the lower your overall cholesterol level, the better your HDL to LDL ratio, and the lower your triglyceride levels, the better your heart outcomes should be. Unfortunately, the theory was not supported by the results. Instead, the trial found, contrary to theory, that the further lowering of "numbers" produced by niacin did not further reduce the risk of cardiovascular events, including heart attacks and stroke… at all. And in fact, this lack of benefit led the National Heart, Lung and Blood Institute, upon the recommendation of its Data Safety Monitoring Committee, to decide to stop the trial 18 months before its planned completion.
The bottom line is that niacin did exactly what it was supposed to. The theory, however, did not. Instead of questioning the theory itself, the researchers instead opted to throw out the supplement that exposed its deficiencies.
Of course, some doctors did point out that this study actually only applies to a limited number of patients. If you are among the majority of patients seen in routine clinical settings, where more than 80 percent are unable to lower their cholesterol levels through statin drugs alone as seen in the study, then niacin might still play a role in your treatment. In other words, the AIM-HIGH only applies to a narrowly defined patient population.
In the end, Dr. William Boden, lead researcher for the study, made a profound leap of faith, and pronounced that the most relevant observation that could be made from the study is that "in this modern era of statin therapy, we've made profound progress in controlling LDL."
Well hooray for statin drugs and bad on natural substances such as niacin.

Deconstructing the myth -- Part 1, HDL/LDL

The medical literature says that LDL cholesterol is bad and that HDL is good. In fact, the relationship is not quite that simple. The basis for understanding low density lipoprotein (LDL) cholesterol came from Nobel Prize winning research conducted in the 1970's and 80's. It clarified the genetic basis behind the inability of some people to remove LDL from their blood. Subsequently, research began to note that effects of LDL cholesterol were somewhat balanced out by levels of high density lipoprotein (HDL) cholesterol in the body. Studies indicated that high HDL correlates with low heart attack numbers. In fact, the primary study that pointed to the benefits of high HDL was the Coronary Drug Project of 1965-1974,4 which examined the effects of niacin on cholesterol levels. It probably should be noted that over a quarter century later, niacin is still the most effective FDA approved means of raising HDL-cholesterol. Then again, niacin also lowers LDL-cholesterol and triglycerides, which meant that it was unclear whether niacin's benefits come from its ability to raise HDL or lower LDL.
In any event, the AIM-HIGH study was designed to make that determination -- sort of. Because of its design, it couldn't determine whether or not niacin alone was beneficial. Nor could it determine whether niacin and statin drugs together were more beneficial than statin drugs alone in people who were "newly" diagnosed with high cholesterol. Its design only allowed it to determine whether or not "adding" niacin to a statin regimen that was already lowering LDL cholesterol provided any benefit. And within those tightly defined parameters, the study was able to conclude that although adding niacin to an already effective regimen of statin drugs improved cholesterol "numbers", it did not seem to provide any actual added health benefit. But is that a knock on niacin, since it did indeed improve the blood serum profile as promised, or a knock on the cholesterol theory of heart disease, since the theory did not perform as expected given the significantly improved cholesterol and triglyceride numbers?

Deconstructing the myth -- Part 2, statin drugs save lives

Statin drugs are considered one of the great achievements of modern medicine -- credited with saving millions of lives. And, encouraged by the pharmaceutical industry, the FDA has regularly lowered the numbers for acceptable cholesterol levels, thus continually expanding the market for these drugs -- not to mention recommendations from pediatric community to lower the age of prospective users to as young as eight.5 It has been joked by some in the medical community that we should just add statin drugs to the water supply and be done with it. (And on a different note, that is already happening to some degree.)

But do statin drugs deserve such adulation?
In truth, studies have indeed confirmed that the use of statin drugs reduces coronary heart disease "incidents" such as heart attack and stroke in populations that use them; and you would think that might settle the issue. But it doesn't! It turns out that medical researchers may have been asking the wrong question.
What is the right question?
Quite simply: do statin drugs help you live longer; do they increase your life expectancy; does the reduced incidence of coronary heart disease "events" add even one single day of life to those who use the drugs? And surprisingly, the answer to this question appears to be a resounding "no"!
Yes, the drugs do in fact lower LDL cholesterol levels. Unfortunately, research shows that lowering cholesterol usually doesn't necessarily lower heart-attack risk. According to a number of studies, patients on statin drugs reap no measurable extension of life unless they had a previous heart attack before taking the drugs.6,7,8,9 And in fact, this is the big news in today's study. Not that niacin doesn't work, because it did. It did exactly what it was supposed to do. It improved cholesterol and triglyceride numbers. The problem is that once again, the cholesterol theory of heart disease failed to perform as advertised. This is the story the mainstream media missed in not reporting the study.
In fact, the claims of success touted in ads for statin drugs are downright misleading -- even the ones that merely talk about reduced incidents. One printed advertisement reads, "Lipitor reduces the risk of heart attack by 36%...in patients with multiple risk factors for heart disease." An asterisk at the bottom includes tiny print that notes that "....in a large clinical study, 3% of patients taking a sugar pill or placebo had a heart attack compared to 2% of patients taking Lipitor." This means that for every 100 people, three who don't take Lipitor will have heart attacks; while two who do take it will have heart attacks anyway. In other words, Lipitor prevents only one heart attack per 100 users.
And yet, the FDA and the medical community keep finding ways to lower the bar and shuttle more and more patients into statin prescriptions, tripling the numbers of users since 2001.

Deconstructing the myth -- Part 3, the entire cholesterol theory of heart disease

I have addressed the cholesterol myth in other newsletters and don't need to repeat the arguments here, other than to summarize the key points.

The evidence that connects cholesterol to heart disease is contradictory at best.
Cholesterol is present in both arteries and veins, and yet veins don't harden and clog up -- only arteries. If cholesterol is the problem, why not?
Statin drugs do lower cholesterol levels, but they don't add one single day to your life unless you've had a previous heart attack. Again, if cholesterol is the problem, why not? As it stands, this runs totally counter to the theory of cholesterol induced heart disease.
Niacin too lowers LDL cholesterol and raises HDL cholesterol, but it also does not seem to extend your life by one single day -- again running counter to the theory of cholesterol induced heart disease.

Keep in mind, the cholesterol theory of heart disease is called into question, not just by me, but by many in the medical community. There is no evidence that forcing cholesterol levels down using drugs adds one single day to your life…unless you've had a previous heart attack. Statin drugs have serious side effects -- including liver damage. And keep in mind, the liver is the organ in your body that actually regulates cholesterol levels in your body. How smart can it be to take a drug to regulates cholesterol by further damaging the organ responsible for regulating cholesterol in the first place?
So, what do we make of this? What connects all the pieces together -- that explains why statin drugs "work" but don't "help"?
In fact, it appears inflammation is the thread that ties everything together. Inflammation damages the walls of the arteries -- but not the veins -- forcing the body to "repair" the damage using cholesterol-based, cement-like plaque to patch over the problem areas. Over time, with continued inflammation and continued repairs, the patches start thickening, hardening, and narrowing the arteries. Statin drugs work, then, not because they lower cholesterol, but because they reduce arterial inflammation. As it turns out, statin drugs suppress T-cell activation and inhibit the release of inflammatory cytokines that are critical mediators of the inflammation response.10,11,12 Statin drugs also help lower C-reactive protein levels -- a known inflammation marker and independent risk factor in the development of ischemic stroke -- again, entirely separate from their effect on serum cholesterol.13,14,15
In the end, cholesterol is blamed, not because it actually harms you, but because, as a key component of arterial plaque, it is found at the scene of the crime.

Conclusion

Which brings us to the final question of the day. Why would you want to use pharmaceutical drugs (statins), whose primary effect (lowering cholesterol), looks to be of virtually no benefit in preventing death from heart disease, merely to cash in on its secondary benefit (coronary inflammation reduction), when other options for reducing inflammation exist that are far more effective…and far safer? Specifically, I'm speaking of proteolytic enzymes.
For further information, I suggest you read:

1. Official World Golf Ranking. (Accessed 19 Nov 2011)
2. The AIM-HIGH Investigators. "Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy." NEJM. 15 Nov 2011.
3. Robert P. Giugliano, M.D., S.M. "Niacin at 56 Years of Age -- Time for an Early Retirement?" NEJM 15 Nov 2011. (Accessed 21 Nov 2011).
4. The Coronary Drug Project Research Group. "Clofibrate and Niacin in Coronary Heart Disease." JAMA. 1975;231(4):360-381.
5. Stephen R. Daniels, MD, PhD, Frank R. Greer, MD, and the Committee on Nutrition. "Lipid Screening and Cardiovascular Health in Childhood." PEDIATRICS Vol. 122 No. 1 July 1, 2008 pp. 198 -208.
6. Thavendiranathan, P., A. Bagai, et al. "Primary prevention of cardiovascular diseases with statin therapy: A meta-analysis of randomized controlled trials." Archives of Internal Medicine 166: 2307-2313.
7. Vrecer, M., S. Turk, et al. "Use of statins in primary and secondary prevention of coronary heart disease and ischemic stroke. Meta-analysis of randomized trials." International Journal of Clinical Pharmacology and Therapeutics 41(12): 567-577.
8. Hayward, R.A., T.P. Hofer, et al. "Narrative review: Lack of evidence for recommended low-density lipoprotein treatment targets: A solvable problem." Annals of Internal Medicine 145(7): 520-530.
9. University of British Columbia. "Do statins have a role in primary prevention? A review by the Therapeutics Initiative of the Department of Pharmacology & Therapeutics of the University of British Columbia." Therapeutics Letter March-April 2010.
10. Di Napoli P, Taccardi AA, Oliver M, et al. "Statins and stroke: evidence for cholesterol-independent effects." Eur Heart J. 2002;23:1908-1921.
11. Vaughan CJ. "Prevention of stroke and dementia with statins: effects beyond lipid lowering." Am J Cardiol. 2003;91:23B-29B.
12. Vaughan CJ, Gotto AM Jr, Basson CT. "The evolving role of statins in the management of atherosclerosis." J Am Coll Cardiol. 2000;35:1-10.
13. Ridker PM, Rifai N, Rose L, et al. "Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events." I. 2002;347:1557-1565.
14. Curb JD, Abbott RD, Rodriguez BL, et al. "C-reactive protein and the future risk of thromboembolic stroke in healthy men." Circulation. 2003;107:2016-2020.
15. Ridker PM, Rifai N, Clearfield M, et al., for the Air Force/Texas Coronary Atherosclerosis Prevention Study Investigators. "Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events." N Engl J Med. 2001;344:1959-1965. http://www.ncbi.nlm.nih.gov/pubmed?term=11430324

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Location of original post HERE. Emphasis added by bd.

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