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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 is its nuisance side-effects, side-effects that we can usually overcome with dosage adjustments 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 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 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.

Slow Release Niacin: These non-prescription slow release forms of Niacin are associated with an increased risk of side-effects and should be avoided.

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
Day Three	750	1000	1000
To Follow	1000	1000	1000

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.

Liver Chemistry: As do stain 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), N-Acetyl Cysteine, or Alpha-Lipoic Acid (the latter two agents are Glutathione precursors). At the office we have Thio-Gel (Lipoic Acid 200 mg, Selenium 70 mcg, and Milk Thistle 200 mg) and N-Acetyl Cysteine 500 mg capsules.
3. Methyl Cycle supplementation (discussed under Homocysteine).

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 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, and 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.

Lab Monitoring: I typically check AST/ALT 4 weeks and 12 after starting Niaspan and 2, 4, and 12 weeks after a patient begins the high dose Niacin regimen; lipids and other target risk factors are checked at the 12 week point.

Additional Thoughts: 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.