Neighbors……greetings!

The inspiration for today’s article comes from my bi-daily jaunt to the grocery store.

Whenever I’m there I can’t resist the urge to cut in front of the seniors waiting in line to use the blood pressure machine.  The excitement from seeing what my numbers will be and the tipsiness that comes from choking off circulation in my arm is a precious high for someone that doesn’t drink or get out much

Since my insouciant antics aren’t doing anything to help these geriatric bystanders get off their medications when I’m in the store, I feel obligated to payback their frustration by cluing them in to a natural remedy to cardiovascular disease here on my digital soapbox. In fact, my secret little cure is so common you almost have to go out of your way to avoid it if you’re buying something that comes in a tablet.

What is this plain-little-vitamin-that-could?

Niacin.

Vitamin By Day, Cholesterol Vacuum By Night

Niacin (not to be confused with niacinamide) is a form of vitamin B3 that allows your body to make something called NAD+, a very useful molecule that controls how energy flows through your body.

You need 20mg of niacin a day to fill your NAD+ gas tank, which is why the RDA is pegged around this amount for the majority of people.

However, if you take significantly more than this (50-100 mg+)  niacin’s effect takes a weird twist and drifts into the metabolic twilight zone.  When your NAD+ pathways are saturated the excess binds to a receptor called Gpr109A which causes your body to go through a lot of changes.

Under your skin it causes a cavalry of inflammatory compounds to show up and relax the capillaries beneath its surface, which causes you to turn red and get a warm tingly feeling that can itch more than you’d like.  Aka, “The Flush.”

I flush from time to time, which you can see here:

Personally, I think the red blushes make me look cute…….like a baby koala.  But the effect is clearly not for everyone, since it’s the biggest reason people stop taking high dose niacin.

More importantly this same receptor is activated in different organs during the flush and changes the way cholesterol flows through your body.

When you flush your adipocytes (fat cells) stop releasing fatty acids which causes your liver to stop producing something called a VLDL.  VLDL is the precursor to LDL, the “bad” cholesterol.  Your body can only make LDL if it has VLDL to begin with, so this effectively causes your liver to turn off the cholesterol spigot.

It also causes your liver to stop making enzymes that take up HDL (the “good” cholesterol) [footnote]the enzyme itself is called beta chain ATP Synthase[/footnote] and block uptake of a protein called Apolipoprotein A1, which is the primary structural protein in HDL’s.  Your HDL particles still deposit cholesterol into your liver, but the remaining HDL in your circulation without the cholesterol causes your HDL-C to increase.

These two mechanisms coincide to produce results that routinely lead to higher HDL-C and HDL-P, modestly lower LDL-C and LDL-P and better triglycerides.

Better yet, the mechanisms that lead to this effect are exclusive to niacin, giving it the potential to compliment other cholesterol therapies that work through different channels.

The summation of high dose niacin (1-2g) on people with impaired blood lipids looks something like this:

[table id=28 /]

Numbers taken from this paper.

Niacin, Meet Statin

The most popular medications used to treat cholesterol are statins.  They work by blocking an enzyme that’s used to make cholesterol called HMG-CoA reductase.  Blocking this enzyme throws a serious monkey wrench in your liver’s cholesterol-making engine because it’s the rate-limiting step in the process and if it doesn’t have enough to synthesize it then your body can only rely on what you get from your diet.

Statins mostly affect your LDL-C, which is the lipid marker least affected by high dose niacin.  Niacin’s biggest affects are on HDL-C, triglycerides, and to a lesser extent HDL-P and LDL-P.

Since they’re both proven and have complimentary mechanisms one would think they’d be a match made in heaven for hammering down your cholesterol levels……and for many years that was the assumption.

For twenty years there was lots and lots of good news about the niacin + statin 1-2 punch being an irreversible blow to dangerous cholesterol levels.

The sentiments echoed in this article reflected the opinions of the medical community at large:

I have personally prescribed niacin for thousands of patients as part of our program to reverse coronary disease. In fact, niacin is the closest thing we have available to a perfect treatment that corrects most of the causes of coronary heart disease.

However, two well-funded studies brought the good news to a screeching halt.

Niacin:  Left for Dead

In 2011 the medical community was gearing up for two high-powered studies that were supposed to cement the niacin/statin combo as THE way to treat athersclerosis.

They were conducted by two research groups titled HPS2-THRIVE and AIM-HIGH.  They had everything going for them:  large sample size, carefully screened and randomized participants, strong control groups,  a study period that lasted years, and a big wad of cash from big pharma companies eagerly awaiting to formalize the supremacy of their cholesterol fighting drugs.

The studies were whopping failures.

Why?

In each case there were modest improvements in HDL and triglycerides, but it wasn’t clinically significant.  And more importantly, there was no decrease in cardiovascular events.  This meant that, despite creating a modest improvement in cholesterol numbers, the addition of niacin didn’t do anything to improve your chances of dying from a heart attack.

To make matters worse, the niacin/statin group had much higher rates of adverse events.  Increased liver damage, rates of infection and impaired blood sugar levels were all part of the collateral damage left by the group with pink cheeks. The side effects were especially pernicious among diabetics, because at high doses niacin can impair insulin sensitivity.  It turns out that in the HPS2-THRIVE study people in the niacin group were at a 32% greater relative risk to develop diabetes during the experiment. [footnote]Note this number refers to relative risk, not absolute risk.  Relative risk is the difference in probability one person or group will have some event happen to them compared to another group.  Absolute risk is the chance it’ll happen at all.  Relative risk can be very high (1% vs. 0.5% is a 100% increase in absolute risk) while absolute risk can still be very low.  In this case the absolute risk of getting diabetes was 1.2%.[/footnote]

The mood towards niacin therapy at this point was grim.

Niacin:  Rising From the Ashes?

The pock-mark left on niacin’s reputation as a safe and effective therapeutic agent for treating cholesterol and lipids has never fully recovered from the AIM-HIGH and HPS2-THRIVE studies.

For a lot of people, the inability to affect cholesterol levels in the presence of a statin has caused many to assume using niacin to help improve cholesterol or triglycerides in any capacity was pointless.

However, like clockwork, whenever there is a controversial experiment an army of naysayers arise from the dust to refute its relevance.

The arguments against the AIM-HIGH and HPS2-THRIVE studies were the following:

• The participants were already cured of low cholesterol.  All participants involved in both studies were pre-treated with statins and had median LDL levels of 63 mg/dl, which is well below the threshold level of 100 mg/dl that’s considered dangerous.  Most people will experience little benefit and have increased risk of side effects from a substance in pharmacological doses if the problem it’s supposed to treat is already healed.
• The groups weren’t properly selected.  The people used in the study weren’t properly sorted for having a particular risk factor that would make them good fits for niacin therapy in the first place.
• Everything that comes out of China is just a little weird.  About 1/3 of the study’s participants were in China, and adverse reactions were disproportionately from this population.
• They took way too much niacin.  Participants were given up to 2g of niacin for the experiments, despite already having healthy cholesterol levels.  That’s like way too much for someone who doesn’t have something wrong with them.
• Niacin was used in combination with other drugs.  In the HPS2-THRIVE study niacin was delivered with another drug called Laropiprant.  Perhaps it was the culprit for the adverse events?
• They didn’t use “true” niacin.  The niacin used in both studies were molecules developed by the pharmaceutical companies that were sponsoring them.  Both were developed to be a “slow release” forms of the vitamin to mute the flushing effect.  However, these forms of the vitamin come with different toxicity risks, particularly at high (1g +) doses.

What’s The Best Way To Take Niacin?

Cumulatively, I think the results of the HPS2-THRIVE and AIM-HIGH studies do a lot to shape our thoughts on what circumstances are best for consuming niacin, but do not refute the body of evidence that demonstrates niacin’s beneficial effects on cholesterol and lipids.

Specifically:

• If your statin is already working well, there’s a good chance adding niacin to it won’t provide additional help, particularly if you already have high HDL levels.
• It should be used with caution if you are diabetic or have high blood sugar.
• It’ll have the most effect for people with low HDL levels and/or high blood triglycerides.
• It shouldn’t be counted on to significantly improve LDL-C, where the effect is modest and not as strong as statins.
• You might want to experiment between regular niacin and slow-release niacin if one isn’t working well.  Slow-release niacin is more likely to cause an adverse effect within the liver since it’s digested more slowly.
• The healthier you are, the less you should take.  If your cholesterol or blood triglycerides are hovering anywhere close to what could be considered normal, taking more than a gram is probably excessive.
• You build up a tolerance to flushing quickly, so it’s best to start small and gradually increase your dosage.   You can get a 100 mg tablet from Source Naturals and split that if you want to start with teensy bites.
• Taking an aspirin 30 minutes before you take niacin helps reduce the flushing effect.

Personally, I like to flush from time-to-time.  It goes by quickly, and once your body goes through it once or twice the edge goes away and you just get a warm, glittery tingle underneath your skin for a half hour or so before everything is normal again.

It’s really nothing to be afraid of, and the absolute chances of something going wrong at less than gram doses are pretty small.

So, as usual, proceed with caution, start small, incrementally experiment, and go from there.

With all this being said, let me bid you farewell by saying “Flush On!”

References:

Markel, Arie.   “The Resurgence of Niacin: From Nicotinic Acid to Niaspan/Laropiprant.”  http://www.ima.org.il/FilesUpload/IMAJ/0/39/19878.pdf.

Miller, Michael.  “Niacin as a Component of Combination Therapy for Dyslipidemia.”  http://www.mayoclinicproceedings.org/article/S0025-6196(11)62465-8/fulltext?refuid=S0149-2918(07)00120-8&refissn=0149-2918#cesec60

Stein, EA, et. al. “Efficacy and Tolerability of Low-dose Simvastatin and Niacin, Alone and in Combination, in Patients With Combined Hyperlipidemia: A Prospective Trial.” http://www.ncbi.nlm.nih.gov/pubmed/10684407?dopt=Abstract

McKinney, J.”Niacin for Dyslipidemia:  Considerations for Product Selection.” http://www.ajhp.org/content/60/10/995.short

Kamanna, VS, et. al. “The mechanism and mitigation of niacin-induced flushing.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2779993/

Brown, Greg, et. al. “Simvastatin and Niacin, Antioxidant Vitamins, or the Combination for the Prevention of Coronary Disease.”  http://www.nejm.org/doi/full/10.1056/NEJMoa011090

HPS2-THRIVE research group.  “Effects of Extended-Release Niacin with Laropiprant in High-Risk Patients” http://www.nejm.org/doi/full/10.1056/NEJMoa1300955#t=articleMethods

AIM-HIGH research group.  “Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy.”  http://www.nejm.org/doi/full/10.1056/NEJMoa1107579