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

Orthomolecular Medicine News Service
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.

References:

Ames BN, Elson-Schwab I, Silver EA. High-dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity (increased K(m)): relevance to genetic disease and polymorphisms. Am J Clin Nutr. Apr 2002;75(4):616-658.

Avila MD, Escolar E, Lamas GA. Chelation therapy after the Trial to Assess Chelation Therapy (TACT): results of a unique trial. Curr Opin Cardiol. Jul 11 2014.

Carlson LA. Nicotinic acid: the broad-spectrum lipid drug. A 50th anniversary review. J Intern Med. Aug 2005;258(2):94-114.

Creider JC, Hegele RA, Joy TR. Niacin: another look at an underutilized lipid-lowering medication. Nature reviews. Endocrinology. Sep 2012;8(9):517-528.

Group HTC, Landray MJ, Haynes R, Hopewell JC, Parish S, Aung T, . . . Armitage J. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. Jul 17 2014;371(3):203-212.

Guyton JR, Bays HE. Safety considerations with niacin therapy. Am J Cardiol. Mar 19 2007;99(6A):22C-31C.

Hoffer A, Osmond H. Treatment of Schizophrenia with Nicotinic Acid. A Ten Year Follow-Up. Acta Psychiatr Scand. 1964;40:171-189.

Horrobin DF. Schizophrenia: a biochemical disorder? Biomedicine. May 1980;32(2):54-55.

Kowalski RA. The New 8-Week Cholesterol Cure: The Ultimate Program for Preventing Heart Disease. Harper Collins; 2001.

Liu CM, Chang SS, Liao SC, Hwang TJ, Shieh MH, Liu SK, . . . Hwu HG. Absent response to niacin skin patch is specific to schizophrenia and independent of smoking. Psychiatry Res. Aug 30 2007;152(2-3):181-187.

Messamore E, Hoffman WF, Janowsky A. The niacin skin flush abnormality in schizophrenia: a quantitative dose-response study. Schizophr Res. Aug 1 2003;62(3):251-258.

Osmond H, Hoffer A. Massive niacin treatment in schizophrenia. Review of a nine-year study. Lancet. Feb 10 1962;1:316-319.

Penberthy WT. Niacin, Riboflavin, and Thiamine. In: Stipanuk MH, Caudill MA, eds. Biochemical, physiological, and molecular aspects of human nutrition. 3rd ed. St. Louis, Mo.: Elsevier/Saunders; 2013:p.540-564.

Smesny S, Klemm S, Stockebrand M, Grunwald S, Gerhard UJ, Rosburg T, … Blanz B. Endophenotype properties of niacin sensitivity as marker of impaired prostaglandin signalling in schizophrenia. Prostaglandins Leukot Essent Fatty Acids. Aug 2007;77(2):79-85.

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