For a time, Niacin, or Vitamin B3, when used in conjunction with statin therapy, was the only supplement approved by the FDA to prevent heart attacks. This stamp of approval from a government agency was the result of a 2001 New England Journal of Medicine (NEJM) study that found Niacin raised HDL, while lowering bad lipid markers, like LDL-C and triglycerides. The 2001 NEJM study found that Niacin provided “measurable benefits in patients with coronary disease and low HDL levels.”
However, the FDA has since withdrawn that approval in light of a new NEJM study that cast Niacin supplementation in a less than favorable light.
But before you give up on Niacin, it’s important to know that the new NEJM study the FDA relied on in changing its mind about Niacin was funded by the drug giant Merck, and it analyzed a population that arguably did not stand to benefit from Niacin supplementation in the first place.
Despite the FDA changing its stance, Niacin supplementation has shown consistent promise as a strategy for lowering lipoprotein a, or Lp(a), which is an independent risk factor for heart disease when elevated.
So, who should we believe?
With quite a bit of seemingly conflicting evidence out there, we set out to answer who, if anyone, stands to benefit from supplementing with Niacin.
Let’s jump in and do a tour of some of the best studies.
Niacin increases HDL-C while lowering LDL-C, triglycerides
One of the knocks on Niacin, other than flushing, a common side effect, is that it can increase blood sugar levels, which is of particular concern to those with diabetes. (R)
To better understand this side effect, and presumably to weigh it against Niacin’s heart health benefits, this study, which appeared in the peer reviewed Journal of the American Medical Association (JAMA), found that Niacin significantly increased HDL-C (“good”cholesterol) and lowered LDL-C (“bad” cholesterol) as well as triglycerides in patients with type 1 diabetes. Type 1 diabetics often have low levels of good cholesterol, which is a problem, because it’s HDL-C that carries cholesterol to the liver where it is disposed of by the body. By contrast, LDL-C is a the type of cholesterol that can deposit in the arterial wall, which eventually leads to a heart attack or stroke. As I mention above, the JAMA researchers were concerned that Niacin could spike blood glucose levels, which is part of the reason the study subjects were type 1 diabetics, but over the two plus years of analysis, glucose levels increased ever so slightly, while HbA(1c) levels (average blood sugar over weeks or months) were unchanged in the patients taking Niacin.
The placebo group did not see an increase in HDL-C, and saw a small increase in both triglycerides as well as LDL-C.
Score one for Niacin.
But we must also ask: do the better LDL-C, triglyceride and HDL numbers add up to fewer heart attacks for those taking Niacin?
Does Niacin prevent heart attacks?
To be sure, the drop in LDL-C and triglycerides paired with the increase in HDL in the JAMA study is impressive, but does it matter?
In 2001, the New England Journal of Medicine (NEJM) found that the answer was yes, that the lipid modifying effects of Niacin had real health benefits when paired with statins, which is presumably the scientific foundation the FDA used in giving Niacin its “blessing.” (R)
Simvastatin plus niacin provides marked clinical and angiographically measurable benefits in patients with coronary disease and low HDL levels.
However, about 13 years later, and with funding from Merck, the NEJM essentially redid the study, this time with patients who had relatively high HDL, and very low LDL-C.
The new NEJM study found that Niacin’s lowering of LDL-C and its ability to increase HDL, didn’t actually result in fewer heart attacks or strokes in a population of 25,673 patients at high risk for a “heart event.” Unlike the 2001 patients, the 2014 NEJM patients were already on statin therapy. They were given Niacin and laropiprant, and then followed for 3.9 years to see how many in the group had a heart attack or stroke.
Although the Niacin group saw a decrease in LDL-C and an increase in HDL, they didn’t suffer fewer heart attacks and strokes, and even worse, had a number of nasty side effects.
But here’s the thing: the NEJM study was funded by the drug giant Merck, and it was conducted in patients who were already at very high risk for heart disease, who were on statins, and who arguably did not stand to benefit from taking Niacin.
In the correspondence section of the NEJM study, which amounts to a dissenting opinion, Christopher M. Rembold, M.D. argues that the less than stellar results for the Niacin group were to be expected based on the low starting LDL-C and high starting HDL numbers of the participants.
The lack of benefit for treatment with niacin and laropiprant that is described in the Heart Protection Study 2–Treatment of HDL to Reduce the Incidence of Vascular Events (HSP2-THRIVE) (July 17 issue)1 was expected, given the low level of low-density lipoprotein (LDL) cholesterol (63 mg per deciliter) and the normal level of high-density lipoprotein (HDL) cholesterol (44 mg per deciliter) prior to randomization.
Dr. Rembold argues that even statin therapy doesn’t show benefit in reducing cardiovascular events in patients with such low LDL-C. Presumably, he’d read the literature from 2001 and saw the obvious differences between the two group’s lipid profiles. His claim, that Niacin may have demonstrated benefit in patients with elevated LDL-C and low HDL, but that the study group was suboptimal for Niacin to show efficacy, is an effective mirror of the 2001 NEJM study.
With statin therapy, a high pretreatment LDL cholesterol level (190 mg per deciliter) is associated with an absolute reduction in the risk of myocardial infarction and death from cardiovascular causes of approximately 1.2 percentage points yearly, an intermediate level (120 to 150 mg per deciliter) with a reduction of approximately 0.6 percentage points yearly, and a low level (approximately 100 mg per deciliter) with a reduction of approximately 0.3 percentage points yearly. With nonstatin therapy (niacin, gemfibrozil, fish oil, and partial ileal bypass), the relationship between the LDL cholesterol level and the absolute risk reduction is similar to that observed with statins.
As we see from the 2001 NEJM study, Dr. Rembold is right on point. The 2001 NEJM study found that Niacin could help patients with low HDL, and high LDL-C, so it cam as no surprise that when the patient group was changes, the results changes.
To give our readers some context, at an average of 63mg/dl, the participants in the NEJM study had very low LDL-C. Boston Heart Diagnostics, an excellent lab based out of, you guessed it, Boston, is where I go to to get lab tests done. Boston Heart lists anything below 100mg/dl as optimal for LDL-C, so presumably, the patient group in the NEJM study was already benefitting from statin therapy, at least as far as their LDL-C numbers showed “on paper.” On a Boston Heart Labs panel their LDL-C would have been well in the green. At last test, my LDL-C was 93 mg/dl, also in the green, but a full 30 points higher than the group studies in the 2013 study.
Previous data shows that stain therapy doesn’t decrease heart events and mortality at these low LDL-C levels, so how would Niacin make that data any different?
Yet, all the headlines after the study were “Niacin doesn’t work.”
Not so. We have two NEJM studies which teach us that the results hinge on the starting HDL and LDL-C numbers.
NEJM study comparison
|Study||Simvastatin and Niacin (2001)||"Extended-Release Niacin with Laropiprant" (2014)|
|Average starting HDL/LDL||31/132mg/dl||44/63mg/dl|
|Notes||Subjects started statins and Niacin with study||Subjects already ill and on statins prior to study, added Niacin and laropiprant|
However, Niacin’s benefits don’t stop with analysis if the best known lipid markers. Let’s talk about Lp(a), the heart health marker everyone should test for, but that isn’t a part of most lipid panels.
Niacin lowers Lp(a)
I’ve already talked a little about Niacin in my post on Lp(a), an independent risk factor for heart disease that is, at least to date, still not listed on most lipid panels. In fact, when my insurance carrier, Blue Cross Blue Shield of Texas, saw the bill for an Lp(a) panel, they attempted to reject the claim. But whether Blue Cross of Texas wants to admit to it or not, Lp(a) is a heart health metric more people should be measuring, and since statin therapy isn’t always effective at lowering Lp(a), natural treatment options are needed. (R)
Multiple studies have shown Niacin to be effective at reducing Lp(a) numbers, and it’s important to realize that when the cholesterol rich Lp(a) isn’t specifically tested for, it “hides out” in the LDL-C number. Since Lp(a) doesn’t respond as well to statin therapy as LDL-C does, some people are unnecessarily put on statin therapy when they have elevated Lp(a) bumping up their LDL-C number. (R)
Niacin appears to be effective at lowering Lp(a).
For example, this study looked at a “combination therapy” treatment plan combining Niacin, omega 3 fatty acid supplements, and a Mediterranean diet as a way to lower Lp(a). The Niacin group saw Lp(a) drop by 23% in 12 weeks.
This study found that Niacin lowers Lp(a), but results depend on the Apo(a) phenotype, which is a combination of genetics and lifestyle.
Here is a report of one patient who lowered Lp(a) by 88% over 5 years with a Niacin and statin combination.
What we know about Niacin’s benefits
Ok, so we know that Niacin lowers Lp(a), at least in some genotypes. We also know that it pretty reliably increases good cholesterol and lowers LDL-C and triglycerides.
The 2014 NEJM study (funded by Merck), showed us that, in patients with very low LDL-C and normal HDL, who are already sick and taking statins, Niacin didn’t help reduce the risk of a heart attack.
However, the first NEJM study showed a clear benefit, and it wasn’t funded by Merck.
As we tour around the studies, the question that I have, that as of yet seems unanswered, is: what does Niacin do for the person who has not yet gone on statins, and isn’t high risk for a cardiovascular event, but who wants to give themselves an “edge” for greater heart health?
We don’t know. Ultimately, the decision whether to take Niacin, especially if you have elevated Lp(a), could come down to the side effects.
Niacin Side Effects
In addition to finding that Niacin didn’t protect against heart attacks, The NEJM study reported an increased risk of serious side effects with Niacin. Below, I’ve included a table which shows their findings.
The data here is pretty grim, with increases in stomach issues, joint problems, flushing, and even infection and bleeding risk increasing. Notably, the NEJM authors found an increased risk for new diabetes cases with Niacin, which is in conflict with the findings of the JAMA study.
When looking at Niacin’s side effects, it’s important to keep in mind that the Niacin group was also taking laropiprant, which is a pharmaceutical with a questionable record of its own. So who do we blame? The Niacin or the laropiprant? Both?
For the reader at home researching Niacin as a natural supplement to improve heart health, it’s safe to say your Niacin won’t have laropiprant in it. The major side effect reported for those supplementing with Niacin is flushing of the skin, which seems to be better tolerated the slower it sets in. If Niacin makes your skin red as a lobster right away, studies show you’re unlikely to want to use it, however, when flushing sets in on a slower timeline, patients don’t seem to mind as much. (R) Only an estimated 5 – 20% of patients discontinue use of Niacin because of flushing. (R)
Anecdotally, my Mother takes Niacin and has no problems with flushing.
Who should consider taking Niacin?
Based on the research above, it seems to me that it’s worthwhile for those with elevated Lp(a) or LDL-C to talk to their doctor about a Niacin supplement.
By contrast, those with high blood sugar numbers, or who have diabetes may want to think twice and try an alternative, like Bergamot.
Last, if you’re one of the 5-20% who experiences flushing with Niacin, it may not be an option for you, although aspirin is supposed to help, as are time released formulas.
Choosing a Niacin supplement
Ok, so you’ve read this post, and taken a look at the research and have decided to discuss a Niacin supplement with your doctor as a means of controlling Lp(a) and LDL-C, and hopefully raising HDL numbers.
How do you choose a product?
According to WebMD, you want to look for a product that has nicotonic acid, as other forms such as nicotinamide and inositol nicotinate do not lower cholesterol levels, and therefore won’t give people the benefits they are looking for.
Beyond just nicotonic acid, you also likely want a time release Niacin so as to reduce the likelihood of flushing. Ortho Molecular makes a high end time release formula if you want the “Cadillac” of Niacin supplements. The Ortho Molecular Time Release Niacin also provides a 500mg dose of nicotonic acid as opposed t0 100mg and 50mg with Bluebonnet and Seeking Health respectively. Most of the Niacin studies administered higher doses, however, it may be worth looking at a smaller dose if you develop side effects at higher doses.