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Amongst the lipid lowering agents available today, Niacin has the longest track record of efficacy, safety, and low cost. The down side of Niacin are B6/methyl group depletion and nuisance flushing, phenomena that we can usually overcome with dosage adjustment and nutritional therapy. Let’s start with the benefits of Niacin, and then review its dosing formats, potential side-effects, and our strategies to minimize them.

1. Decreases LDL and total cholesterol (less than HMG Co-A Reductase inhibitors - statins) while increasing HDL (better than statins) and lowering Lp(a) (statins may raise Lp(a)).
2. With or without concomitant statin therapy, Niacin blunts IMT progression.
3. Improves endothelial function (documented in patients with low HDL levels).
4. Decreases heart attack and cardiovascular adverse event rate in humans.

Niaspan: This prescription, slow release form of Niacin is taken at bedtime, the idea being that you will not experience flushing as you are asleep. Start with 500 mg, and if all is going well increase to 1000 mg (two 500 mg tabs) in two weeks. Niaspan is not generic and is relatively expensive.

Niacin: This over-the-counter agent provides the full complement of Niacin’s benefits at a fraction the cost of Niaspan, but the cost will be out-of-pocket. Regular Niacin is more likely to cause flushing, but it is not more likely than Niaspan to cause important side-effects.

Nutriceutical Slow Release Niacin – Niaspan-like formulations designed to minimize flushing - Options:
A. Niacin CRT 500 mg (DfH NCRT60) or 750 mg (DfH NCT750) once or twice a day with food.
B. Niatain (M) 500 mg, once or twice a day with food. Links to DfH (Designs for Health) and M (Metagenics) are available on heartfixer.com.
C. Inositol Hexaniacinate: Often referred to as “flush free Niacin”, this form of Niacin does not cause significant flushing, but its lipid lowering benefit is minimal as compared to that of Niacin’s other forms. To have an effect doses up to 1500 mg three times a day are needed. We use Inositol Hexaniacinate only when no other options are available.

Combination Therapy: The combination of Niacin with a Statin will synergize with respect to lipid and IMT reduction (but side effect potential is also increased) and we makes judicious use of this synergy.

Flushing: Two biochemical phenomena play a role in flushing related to Niacin. Niacin leads to the release of fatty acids from our cell membranes, which can then be converted into vasodilatory prostaglandins, which produce the flushing (cutaneous blood vessels dilate, your skin reddens, and you may experience flushing or itching). This will not hurt you but is certainly a nuisance. Aspirin blocks formation of all prostaglandins, and if taken 30 minutes before your evening Niaspan dose, will often block or at least blunt the sensation of flushing (a daily dose of Ibuprofen does the same). A balanced program of fatty acid supplementation (so you have a healthy cell membrane to work with) may blunt flushing and is also a plus for your cardiovascular and overall health. The second mechanism is histamine release, which can be blunted by Benadryl (taken prior to your evening Niaspan, Benadryl may also help your fall asleep) or Bioflavonoids such as Pycnogenol/Grape Seed Extract, taken throughout the day (Bioflavonoids have additional health and cardiovascular benefits). If Histamine stores are depleted by Niacin, then there can be no flushing, the basis for the rapid loading or “jump in the cold lake” approach to Niacin dosing strategy (in mgs) presented below.

If you start with a low dose of regular Niacin, and then slowly build up the dose, you will experience a mild to moderate degree of flushing with each dose increase, kind of like when you wade into a cold lake step by step. Conversely, if you rapidly escalate the Niacin dose, Histamine will be depleted, such that flushing will no longer occur. You will be able to take a high dose of Niacin without flushing. However, if you put Niacin on hold for several days, flushing will return as you resume Niacin, as your body will have had enough time to regenerate its Histamine stores. If you take the “jump right in to the lake” approach, you will experience flushing for several days, but following that you should be “flush free”.

	AM	Mid-Day	PM
Day One	250	250	500
Day Two	500	500	750
To Follow	750	750	750

If you cannot tolerate the transient flushing associated with the “jump in the lake” approach, you can start Niacin at a low dose (100 to 250 mg) and slowly increase it, aiming for 1-2,000 mg per day. Niatain and Niacin CRT can also be utilized within the above dosing format, taking each dose with food.

Liver Chemistry: As do statin drugs, Niacin can cause a reversible rise in liver chemistries (the transaminases, AST and ALT). A mild rise in AST/ALT is not a major concern, and probably does not reflect actual biochemical dysfunction of the liver. Larger bumps in the AST/ALT values are of concern. When liver chemistries rise but we have a need to keep you on Niacin (remember, these are all risk: benefit decisions), the following strategies can be used:
1. Remove any other substances that might be stressing liver function (e.g. alcohol, high dietary carbohydrate intake, other prescription drugs).
2. Nutritional intervention with Silymarin/Milk Thistle 140 mg (DfH-MLK090), N-Acetyl Cysteine 500 mg (E-T60029) or 900 mg (DfH-NAC120), or Alpha-Lipoic Acid 300 mg (M) - (the latter two agents are Glutathione precursors). DFH Hepatatone (DfH-HEP120), 4 daily, provides 600 mg NAC, 500 mg Milk Thistle, and four liver-protective herbal agents.

Blood Sugar: Niacin may increase blood sugar values slightly in diabetics and in pre-diabetics (individuals with Metabolic Syndrome). Despite the rise in blood sugar, Niacin will still have an anti-plaque effect (beneficial effect on Carotid IMT – please see DVD). Still, if we are on the fence regarding beginning you on Niacin, the presence of diabetes will push us away from Niacin and towards an alternative approach.

Homocysteine: Homocysteine levels may increase in relation to Niacin, as Niacin metabolism in the liver places a strain on the Methyl cycle. Specifically, SAMe is used up, methylating Niacin. It appears that the metabolic side effects of Niacin (elevated liver chemistries and blood sugar), and the rise in Homocysteine sometimes observed with Niacin treatment, are related to Methyl group depletion. In animals, Niacin wastes B6 and elevates Homocysteine, but these side effects do not occur, and Niacin’s lipid lowering benefit is maintained, if B6 is given along with Niacin. In humans, Methionine (SAMe precursor) 1000 mg twice a day prevented the rise in blood glucose and liver chemistries seen in a control group that received Niacin alone. Homocysteine metabolism and Methyl cycle supplementation is discussed on the heartfixer.com website, but all of our patients are advised to take a broad-spectrum 6 tab/day multi that contains B6, folic acid, and B12. I may add in 50 mg of P-5-P (the active form of B6) as you begin niacin therapy. If Homocysteine does rise, then additional steps can be taken (methylated B12, folate, or SAMe).

Abdominal Pain/Peptic Ulcer Disease/Pancreatitis: Rarely do we see this, but some people experience abdominal discomfort or GI dysfunction related to Niacin.

Gout: Gout may be precipitated by Niacin, but just as in the case of serious GI dysfunction, I have not seen this. Acute gout can be addressed with colchicine, which also provides for plaque stabilization.

Lab Monitoring: I typically check AST/ALT 4 weeks after starting niacin, with AST/ALT, lipids, and homocystine determinations at the 12-week point.

Additional Thoughts:
A. Please do not confuse Niacin with Niacinamide. The latter does not lower lipids, and is used in the treatment of Osteoarthritis. Niacin, known otherwise as Nicotinic Acid, has nothing to do with Nicotine, as found in cigarette smoke. If you cannot tolerate the transient flushing associated with the “jump in the lake” approach, you can start Niacin at a low dose (100 to 250 mg) and slowly increase it.

B. Clinical trial confusion – Niacin was the first therapeutic agent demonstrated to decrease heart attack risk. However, as it cannot be patent protected (outside of the Niaspan form) the pharmaceutical industry (which funds cardiology journals and meeting) has nothing to gain from the use of niacin. There will be no Niacin TV adds during the Super Bowl. One company created a formulation of niacin with an agent designed to blunt nuisance flushing. When added to high dose statin therapy, this agent provided no additional benefit. The problem here is that:
A. The anti-flushing agent may have had an independent negative effect.
B. With high dose statin therapy there was little room left for improvement.
C. B6 was not provided and homocysteine was not addressed – this is a big deal.

Niacin blunts the recycling of B6, a negative that we can overcome with P-5-P supplementation (just as we recommend Co-Enzyme Q10 when we prescribe a statin we need to make sure that B6 nutriture is addressed when Niacin is recommended). Our body metabolizes niacin via methylation. Thus, SAMe is used up during niacin metabolism, SAH is formed, the SAMe to SAH ratio falls, and 300 chemical reactions that depend on a physiologic SAMe to SAH ratio go off line. You do not hear about this from American physicians or from TV adds as our nutritional approaches to homocysteine metabolism are not patentable (you can’t patent Mother Nature).

It is my thinking that if the studies on niacin were repeated, with concomitant attention to B6 and Methyl Cycle status, that outcomes would be vastly improved. As we want only good outcomes for you, when you take niacin we will pay attention to these issues.

Please remember, every drug, and some nutritional interventions will lead to depletion of one or more nutrients. If we pay attention to this phenomenon, you get the beneficial effects of the intervention, without the nutritional depletion-related down side. This is what Integrative Cardiology is all about.