Niacin is/was/will always be the Good One - Penberthy

Laropiprant is the Bad One; Niacin is/was/will always be the Good One

by W. Todd Penberthy, PhD

(OMNS July 25, 2014) Niacin has been used for over 60 years in tens of thousands of patients with tremendously favorable therapeutic benefit (Carlson 2005). In the first-person NY Times best seller, "8 Weeks to a Cure for Cholesterol," the author describes his journey from being a walking heart attack time bomb to a becoming a healthy individual. He hails high-dose niacin as the one treatment that did more to correct his poor lipid profile than any other (Kowalski 2001). Many clinical studies have shown that high doses of niacin (3,000-5,000 mg plain old immediate release niacin taken in divided doses spread out over the course of a day) cause dramatic reductions in total mortality in patients that experienced previous strokes (Creider 2012). High dose niacin has also been clinically proven to provide positive transformational relief to many schizophrenics in studies involving administration of immediate release niacin in multi-thousand-milligram quantities to greater than 10,000 patients (Hoffer 1964; Osmond 1962). Most importantly, after 60 years of use the safety profile for niacin (especially immediate release niacin) remains far safer than the safest drug (Guyton 2007).

Bad Reporting

So why has the media suddenly presented the following niacin alarmist headlines in response to the most recent study in the New England Journal of Medicine?

"Niacin drug causes serious side effects, study says" - Boston Globe, 7/16/14

"Niacin safety, effectiveness questioned in new heart study" - Healthday News, 7/17/14

"Doctors say cholesterol drug risky to take" - Times Daily, 7/16/14

"Niacin risks may present health risks claim scientists" - Viral Global News, 7/17/14

"Studies reveal new niacin risks" - Drug Discovery and Development, 7/17/14

"No love for niacin" - Medpage Today, 7/17/14

"Niacin could be more harmful than helpful" - Telemanagement, 7/18/14

The truth of the matter is that the study quoted and used laropiprant (trade names: Cordaptive and Tredaptive). Laropiprant is a questionable drug and the results say next to nothing about niacin. The study compared over 25,000 patients treated with either niacin along with laropiprant, or placebo. The patients in this study had previous history of myocardial infarction, cerebrovascular disease, peripheral arterial disease, or diabetes mellitus with evidence of symptomatic coronary disease. The side effects observed in those who took the laropiprant-niacin combination were serious and included an increase in total mortality as well as significant increases in the risk for developing diabetes.

For responsible reporters, this should have raised the question of which compound, the drug laropiprant, or the vitamin niacin, is the culprit.

Such side effects have not been seen in over 10 major clinical trials of niacin involving tens of thousands of patients, not in over 60 years of regular usage of niacin in clinics across the country. However, niacin causes a warm flush on the skin. Some people find the warm niacin flush uncomfortable, although many people enjoy this temporary sensation. In this study, niacin was given in combination with laropiprant, a drug that prevents the niacin flush. By including a dose of laropiprant along with the niacin to eliminate the flush, the thought was that more patients could benefit from niacin without complaint. But in fact the niacin flush is healthy. A reduced flush response to niacin is a diagnostic for increased incidence of schizophrenia, and this assay is now widely available (Horrobin 1980; Messamore, 2003; Liu 2007; Smesny, 2007).

Problems with Laropiprant

So what about the other half of the combo, the drug laropiprant?

• Laropiprant has never been approved by the FDA for use in the USA and when taken alone has been shown to increase gastrointestinal bleeding. *
• Laropiprant interferes with a basic prostaglandin receptor pathway that is important for good health.
• Last year Merck announced it would withdraw laropiprant worldwide due to complaints from continental Europe. Therefore the clinical trials in this most recent study could only be performed in the UK, Scandinavia, and China.

So why did so many media outlets and even some MDs conclude that niacin was the problem? Simple: none of the headlines mentioned laropiprant, which is quite clearly the real culprit that caused the side effects reported. The simplest way to put it is to say that sensational stories promulgated by the media are quite often completely wrong. This suggests a hidden agenda.

Confusing and fantastical headlines can increase readership for hysteria-based business models. Which headline is likely to garner the greatest attention: "Laropiprant is a Dangerous Medication that has Not Been Approved by the FDA" or "Niacin Causes Serious Side Effects"? The correct headline would be, "Niacin doesn't cause serious side effects; drugs do."

Why the B Vitamins Are So Important

The B vitamins were discovered due to terrible nutritional epidemics: pellagra (niacin/vitamin B3 deficiency) and beriberi (thiamine/vitamin B1 deficiency). We are very sensitive to a deficiency of niacin. Over 100,000 people died in the American south in the first two decades of the 20th century due to a lack of niacin in their diet. It was perhaps the worst nutritional epidemic ever observed in modern times, and was a ghastly testimony to how vulnerable the human animal is to niacin deficiency. The pellagra and beriberi epidemics took off shortly after the introduction of processed foods such as white rice and white flour. Poor diets, mental and physical stresses, and certain disease conditions have all been proven to actively deplete nicotinamide adenine dinucleotide (NAD) levels, causing patients to respond favorably to greater than average niacin dosing.

How is it possible that niacin can be useful for many different conditions? It seems too good to be true. The reason is that niacin is necessary for more biochemical reactions than any other vitamin-derived molecule: over 450 different gene-encoded enzymatic reactions (UniproKB database of the Swiss Institute of Bioinformatics; (Penberthy 2013)). That is more reactions than any other vitamin-derived co-factor! Niacin is involved in just about every major biochemical pathway. Some individuals, who have a genetically encoded amino acid polymorphism within the NAD binding domain of an enzyme protein, will have a lower binding affinity for NAD that can only be treated by administering higher amounts of niacin to make the amount of NAD required for normal health. Genetic differences such as these are why many individuals require higher amounts of niacin in order for their enzymes to function correctly (Ames 2002).

It is a deadly shame that the media so often ignores this information. Fortunately, many physicians will see through the recent headlines that give misinformation about niacin, having already personally witnessed how effective high dose niacin therapy is for preventing cardiovascular disease.

Nutrients are the Solution, Not the Problem

So what is the solution? At the end of the day the data on patients with problem cholesterol/LDL levels still support 3,000-5,000 milligrams of immediate-release niacin as the best clinically-proven approach to maintaining a healthy lipid profile. Niacin in 250mg to 1000mg doses can be purchased inexpensively from many sources. Extended-release niacin is the form of niacin that is most frequently sold by prescription, but it has more side effects than immediate release (plain old) niacin. . . and it costs much more.

Tangential to niacin but pointed to cardiovascular disease, conventional medicine is finally beginning to respect chelation therapy as an approach owing to the recent unparalleled positive clinical results for cardiovascular disease patients with diabetes - up to 50% prevention of recurrent heart attacks and 43% reduction in death rate from all causes (Avila 2014). Some times chelation therapy can be expensive. However, there are other inexpensive approaches include high dose IP6 therapy that are yet to be conventionally appreciated. Other supplements desirable for any ideal cardiovascular disease: a nutritional regimen include additional vitamin C, magnesium, coenzyme Q, fat soluble vitamins (A, D, E, and K2), and grass-fed organic butter. Your ideal intake varies with your individuality.

Nutrients such as niacin you need. Media misinformation you don't.

====================================================================

Read the complete article here.

British Heart Foundation does not want to engage with the troubling science on sterols - Briffa

The medical director of the British Heart Foundation does not want to engage with the troubling science on sterols

By Dr John Briffa on 9 August 2013  

 

Last month, I wrote a blog post about how there was no evidence that cholesterol-lowering ‘stanols’ and ‘sterols’ (found in some margarines and other ‘functional foods’) have benefits for health. In fact, the National Institute for Health and Care Excellence explicitly states that they should not be used. Yet, the British Heart Foundation (BHF) recommends the use of stanols and sterols, though I wondered if this might have something to do with the fact that one of its corporate partners is Flora pro.activ (a brand of sterol-enriched foods made by Unilever).

On the 17th July, I emailed the BHF about this. Here’s my email to them:

The National Institute for Health and Care Excellence has this to say about dietary stanols and sterols: “People should not routinely be recommended to take plant sterols and stanols for the primary prevention of [cardiovascular disease].”
We are also advised by NICE that: “There is a need for trials to test both efficacy and effectiveness of plant sterols and stanols in people who are at high risk of a first CVD event.

 These trials should test whether plant sterols or stanols change lipid profiles and reduce CVD events under best possible conditions. Randomised controlled trials are needed to test the effectiveness of advising people who are at high risk of experiencing a first CVD event to include food items containing plant sterols or stanols in a low-fat diet. The trial should last for at least 2 years and should consider appropriate outcomes.”

Yet, I notice that the BHF advocates stanols and sterols. Can someone explain the discrepancy, and whether the BHF believes the fact that Flora pro-avtiv is a corporate partner of represents a financial conflict of interest?
 

On the 30th July, I got a reply from Professor Peter Weissberg, the medical director of the BHF. Here are the highlights from his email:

• They are not suggesting that plant sterols/stanols can prevent a heart attack
• They do help to reduce LDL cholesterol, which is a risk factor for heart disease
• Their information reflects this and has not been altered by their fundraising partnership with Flora pro.activ.
• The BHF  has a very clear set of principles on the basis of which they work with commercial organisations.
• The amount of money they take from Flora pro.activ is a tiny percentage of their overall budget.

The same day, I emailed Professor Weissberg again, this time questioning the presumed benefit of LDL-cholesterol reduction, but also to draw his attention, should he not be aware of it already, of the considerable body of evidence which suggests sterols have the potential for harm. Here’s my email:

 

Dear Professor Weissberg
Thank you for getting back to me.

As you allude to, sterols/stanols have never been demonstrated to have clinical benefit, and it appears your support of them rests on their ability to reduce LDL-cholesterol levels (which you say is a risk factor for heart disease). Unfortunately, as I’m sure you’ll know, reduction of LDL-cholesterol most certainly does not assure clinical benefit. Ezetimibe – which has a similar mechanism of action to sterols/stanols – is a case in point.

Also, if arsenic and cyanide were found to be effective LDL-cholesterol reducing agents, it still would not make sense to recommend them for people for the reduction of cardiovascular disease risk, right?

The reason that I use this example is because, as you may know, there is a considerable body of evidence which suggests that sterols/stanols may have adverse effects on health. These are very well summarized in a paper published in the European Heart Journal in 2009 [Weingartner O, et al Controversial role of plant sterol esters in the management of hypercholesterolaemia. Europlean Heart Journal 2009;30:404-409]. If you have not already read it, I urge you to.

In this paper, the authors cite evidence linking the presence of sterols in the blood with an increased risk of cardiovascular disease. For example:

…there is evidence that elevated levels of plant sterols are associated with an increased cardiovascular risk. Glueck et al [Relationships of serum plant sterols (phytosterols) and cholesterol in 595 hypercholesterolemic subjects, and familial aggregation of phytosterols, cholesterol, and premature coronary heart disease in hyperphytosterolemic probands and their first-degree relatives. Metabolism 1991;40:842–848] were the first to report that elevated plant sterols might be a risk factor for coronary heart disease. In a study with 595 hypercholesterolaemic patients, they found that slightly elevated plasma levels of plant sterols were a heritable marker for an increased cardiovascular risk.

Rajaratnam et al [Independent association of serum squalene and noncholesterol sterols with coronary artery disease in postmenopausal women. J Am Coll Cardiol 2000;35:1185–1191]…found that in postmenopausal women, plant sterols were independently associated with coronary heart disease in a multivariate analysis. These findings were confirmed by Sutherland and his team in a study involving both sexes over all age groups [Association of plasma noncholesterol sterol levels with severity of coronary heart disease. Nutr Metab Cardiovasc Dis 1998;8:386–391].

The Scandinavian Simvastatin Survey Study (4S study) also identified a subpopulation of coronary artery disease patients with low endogenous synthesis of cholesterol and high absorption of cholesterol and plant sterols. The subjects of this subpopulation had the highest levels of plant sterols and the highest risk of recurrent coronary events despite lower levels of serum cholesterol due to simvastatin ingestion [Baseline serum cholestanol as predictor of recurrent coronary events in subgroup of Scandinavian simvastatin survival study. Finnish 4S Investigators. BMJ 1998;316:1127–1130]

Larger epidemiological studies reported similar data. Results of the PROCAM-study showed that patients afflicted with myocardial infarction or sudden cardiac death had increased plant sterol concentrations [Plasma sitosterol elevations are associated with an increased incidence of coronary events in men: results of a nested case-control analysis of the Prospective Cardiovascular Munster (PROCAM) study. Nutr Metab Cardiovasc Dis 2006;16:13–21]. Upper normal levels of plant sterols were associated with a three-fold increase of risk for coronary events among men in the highest tertile of coronary risk according to the PROCAM-algorithm.

Similar data are available for the plant sterol campesterol from the MONICA/KORA-study. In this prospective study, campesterol correlated directly with the incidence of acute myocardial infarction [Abstract 4099: elevated campesterol serum levels–a significant predictor of incident myocardial infarction: results of the population-based MONICA/KORA follow-up study 1994–2005. Circulation 2006;114:II_884].

This is all epidemiological evidence, of course, but it supported by several animal, in vitro and clinical experiments that, I think, give us genuine cause for concern. Again, from the European Heart Journal paper [Weingartner O, et al Controversial role of plant sterol esters in the management of hypercholesterolaemia. Europlean Heart Journal 2009;30:404-409]:

Current experimental findings from our own research group show that a diet supplementation with plant sterol esters that is equivalent to a commercially available spread induces endothelial dysfunction and leads to an increase of ischaemic stroke size in wild-type mice [Vascular effects of diet supplementation with plant sterols. J Am Coll Cardiol 2008;51:1553–1561].

…in a clinical study, we demonstrated that patients who were consuming plant sterol ester enriched margarine had increased concentrations of plant sterols in cardiovascular tissue [Vascular effects of diet supplementation with plant sterols. J Am Coll Cardiol 2008;51:1553–1561].

Further mechanistic data suggest that vascular deposits of sterols, when compared with cholesterol, result in increased oxidation and release of oxygen radicals [Oxidized plant sterols in human serum and lipid infusions as measured by combined gas-liquid chromatography-mass spectrometry. J Lipid Res 2001;42:2030–2038].

…the induction of apoptosis is not limited to tumour cells, but extends also to vascular cells. Recent in vitro experiments demonstrated that the plant sterol sitosterol exerts a strong cytotoxic propensity inducing apoptosis in human endothelial cells, revealing detrimental effects on the vasculature [Beneficial or harmful influence of phytosterols on human cells? Br J Nutr 2008;100:1183–1191].
In fact, the first experimental study reporting negative cardiovascular effects dates back to the year 2000. Ratnayake et al.  [Vegetable oils high in phytosterols make erythrocytes less deformable and shorten the life span of stroke-prone spontaneously hypertensive rats. J Nutr 2000;130:1166–1178 reported that increased serum levels of plant sterols increase rigidity of erythrocytes and shorten the life span of stroke-prone spontaneously hypertensive (SHRSP) rats.

These findings were the reason for Health Canada, the federal department responsible for helping Canadians maintain and improve their health, to raise significant safety issues and not to allow functional foods enriched with plant sterol esters to be sold in Canada.

I am sure you must be very busy, but please take some time to consider this evidence. From what I can see from the research, we have no evidence at all that sterols/stanols improve clinical outcomes, and considerable evidence linking them with potential for harm. Until we have positive evidence regarding outcomes, wouldn’t the most prudent and safety-conscious thing be to not recommend sterols/stanols (as NICE does)?

Thank you for your explanation regarding your corporate partners. If the funds derived from this relationship are so low, why not sever the link and have no conflict of interest at all, here?
I look forward to hearing from you.
Kind regards
John Briffa
 

On the 6th August, I got this response from Professor Weissberg:

Dear Dr Briffa
Thank you for your further email on this subject. I am aware of a large number of publications, of varying quality and validity, on the subject of plant stanols and sterols and their potential benefits and harms. I would prefer not to enter into a debate on any one of them since they all have their strengths and weaknesses.

So, as with so much in science, interpretation of the data is not as straightforward as is sometimes presented. Nevertheless, we are agreed that, ideally, one would like to see appropriately designed outcome trials to test their role in protection against cardiovascular events. In the absence of such data (and I doubt they will ever be produced), it is a matter of judgement as to whether or not plant stanols should be included as part of a wider strategy to reduce cardiovascular risk, and different national bodies have come to different conclusions.

In drawing this correspondence to a close I would conclude by saying that the BHF only enters into partnerships after careful consideration of all the pros and cons of so doing. As discussed previously, the main objective of the partnership with Unilever is to utilise their considerable reach to help us highlight the risk of CVD to women.

I thank you for your interest in this project and assure you we take seriously all feedback we receive.
Yours
 

Notice here how Professor Weissberg makes no comment at all on the specifics of the studies, nor puts up one scrap of evidence to refute the concerns raised. And what are we to glean from his writing: “In drawing this correspondence to a close…” To me, that gives the impression Professor Weissberg wants to hear no more from me (or perhaps anyone else) on the matter. Case closed!
I think we deserve better to be honest. I genuinely believe that, based on the evidence, there is a case to answer regarding the health effects of sterols, and it’s simply not good enough for Professor Weissberg to dismiss the evidence based on rhetoric to do with, supposedly, the evidence being of ‘varying quality and validity’. This is true of all science, so is Professor Weissberg suggesting we just go back to the dark ages and believe what suits us?

How many people do you imagine look to the BHF as being a reliable and credible organisation dedicated to our heart health? Lots, I would imagine. How do you think they would feel to know that when legitimate concerns are raised about products they recommend (some of which are made by a company the BHF partners with), their medical director just flatly refuses to engage with the science?
There is absolutely no evidence that sterols benefit health, but it seems the BHF is going to recommend them anyway, even in light of significant evidence suggesting they have the potential for harm.

Professor Weissberg seems to claim that the BHF’s relationship with Unilever does not compromise them. In fact, Unilever is helping them raise awareness about the risk of cardiovascular disease in women! I wonder how many of these women will be concerned enough to put their faith in utterly bogus food products enriched with sterols?
============================================================
Read the complete article here.

Niacin references.

Niacin seems to be in the news a lot of late. Here is a reference to some sources of some info re the subject worthy of a read by any interested.

Niacin - A Critical Component to the Management of Atherosclerosis.pdf

 

How does nicotinic acid modify the lipid profile.pdf

Effects of Niacin on Lipoprotein Subclass Distribution.pdf

Effects of Niacin on LDL Particle Number.pdf

Extended-Release Niacin Blocks Postprandial HDL Reduction.pdf

Crestor Alone or With ER Niacin-New Therapeutic Option.pdf

Does Niacin Lower Blood Pressure.pdf

The Facts Behind Niacin.pdf

Attainment of Combined Optimal Lipid Values With the Use of Niacin.pdf

Niacin Curbs Atherosclerosis but Impacts Glucose Metabolism.pdf

Hepatotoxic Effects of Lipid-altering Agents.pdf

Efficacy of Extended-Release Niacin.ppt

Dayspring - Niacin (application).pdf

Dayspring - Niacin Mechanism of Action.pdf

Effects of Statin and Niacin on Plaque Stability, Plaque Regression, Inflammation and Oxidative Stress.pdf

There also is Dr Daysprings writing on it in his lipid library on site here worth comparing.
http://heartlifetalk.com/forums/yaf_postst949_Lipid-Center--Dr-Thomas-Dayspring-Resources.aspx

===========================================Updated 3/30/2013

Shocking Cholesterol News - Suzy Cohen

Shocking Cholesterol News

Dear Pharmacist,

I saw Dr. Oz interview a doctor on television about cholesterol. The guest said your total cholesterol doesn’t matter and I read that in your book 6 years ago. Suzy, I take a statin, and do a “Lipid Profile” annually. Is this okay? –M.D., Austin, Texas

Answer: No, it’s not okay, and I’m about to shock everyone, unless you’ve read my books, then this will be review.

Recently I wrote a column about LDL and that we should not necessarily strive to lower it. We need to know the type and number of LDL particles. For example, Lipoprotein A  or “Lp(a)” and another called apolipoprotein B or “Apo B” are two subtypes of LDL particles. These particular scores directly affect your cardiovascular risk. Do you have those numbers on your lab test? I bet you don’t.

In my first book, The 24-Hour Pharmacist from 2007 and many syndicated columns I’ve explained that statins are not very effective in reducing LDL particle number or Apo B and usually do not increase the size of your LDL particles, that’s why I don’t encourage them.

It’s confusing for consumers (and physicians who unwittingly accept drug propaganda) because studies conclude statins reduce total LDL. And yes, they do reduce “total” LDL, they are also excellent anti-inflammatories so they are not completely without merit. But I’m bent on you reducing Lp(a) and Apo B, the dangerous subtypes of LDL known to raise risk for heart attack and stroke.  One day I’ll tell you which vitamin reduces those bad boys, since drugs can’t, but now, back to this testing dilemma.

I’ll never submit myself for a routine “Lipid Profile” because it would waste my money. Half the people who have heart attacks have normal total cholesterol. If your results shows a low LDL (considered the bad particle), then you may assume you’re okay but you see, a low total LDL score doesn’t say much. Your triglycerides might be through the roof! You may have a huge concentration of dangerous Lp(a) and Apo B, subtypes of LDL that are never measured in that basic lipid profile.

Likewise, you may be happy with your high HDL cholesterol score, (HDL is considered a good cholesterol), but what if you have the wrong kind of HDL particles? Yeah, some HDL is bad, you didn’t know that?!  You’re still at very high risk.  These basic “Lipid Profiles” don’t provide the crucial details. It’s like a car mechanic who you hire to fix your engine, but you only let him look at the hood of your car, he can’t open the hood to see inside!

The better tests, sometimes covered by insurance measure particle size, type and sometimes the actual number of LDL and HDL particles. I urge you to ask your physician to order tests from Berkeley HeartLab, a leader in this field. There’s also another one called the “VAP Test” by Atherotec Diagnostics and finally, the “NMR Lipoprofile” by LipoScience.

http://www.dearpharmacist.com/2013/01/16/shocking-cholesterol-news/

==========================================================

Total cholesterol doesn’t matter...Cohen

Dear Pharmacist,

 

I saw Dr. Oz interview a doctor on television about cholesterol. The guest said your total cholesterol doesn’t matter and I read that in your book 6 years ago. Suzy, I take a statin, and do a “Lipid Profile” annually. Is this okay? –M.D., Austin, Texas
 

Answer: No, it’s not okay, and I’m about to shock everyone, unless you’ve read my books, then this will be review.
 

Recently I wrote a column about LDL and that we should not necessarily strive to lower it. We need to know the type and number of LDL particles. For example, Lipoprotein A or “Lp(a)” and another called apolipoprotein B or “Apo B” are two subtypes of LDL particles. These particular scores directly affect your cardiovascular risk. Do you have those numbers on your lab test? I bet you don’t.
 

In my first book, The 24-Hour Pharmacist from 2007 and many syndicated columns I’ve explained that statins are not very effective in reducing LDL particle number or Apo B and usually do not increase the size of your LDL particles, that’s why I don’t encourage them.
 

It’s confusing for consumers (and physicians who unwittingly accept drug propaganda) because studies conclude statins reduce total LDL. And yes, they do reduce “total” LDL, they are also excellent anti-inflammatories so they are not completely without merit. But I’m bent on you reducing Lp(a) and Apo B, the dangerous subtypes of LDL known to raise risk for heart attack and stroke. One day I’ll tell you which vitamin reduces those bad boys, since drugs can’t, but now, back to this testing dilemma.

I’ll never submit myself for a routine “Lipid Profile” because it would waste my money. Half the people who have heart attacks have normal total cholesterol. If your results shows a low LDL (considered the bad particle), then you may assume you’re okay but you see, a low total LDL score doesn’t say much. Your triglycerides might be through the roof! You may have a huge concentration of dangerous Lp(a) and Apo B, subtypes of LDL that are never measured in that basic lipid profile.
 

Likewise, you may be happy with your high HDL cholesterol score, (HDL is considered a good cholesterol), but what if you have the wrong kind of HDL particles? Yeah, some HDL is bad, you didn’t know that?! You’re still at very high risk. These basic “Lipid Profiles” don’t provide the crucial details. It’s like a car mechanic who you hire to fix your engine, but you only let him look at the hood of your car, he can’t open the hood to see inside!
 

The better tests, sometimes covered by insurance measure particle size, type and sometimes the actual number of LDL and HDL particles. I urge you to ask your physician to order tests from Berkeley HeartLab, a leader in this field. There’s also another one called the “VAP Test” by Atherotec Diagnostics and finally, the “NMR Lipoprofile” by LipoScience.
 

===========================================================

Read the complete atricle here.