David Leonardi, M.D. ABAAM, CNS

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Statin Alternatives

David Leonardi, M.D., ABAAM, CNS

There are prescription drugs that may be used as alternatives to statins to improve the lipoprotein profile. This discussion is limited to nutritional supplements available without a prescription. It includes the following:

Niacin

Red Yeast Rice

Policosanol

Plant sterols and stannols will be added soon.

Niacin

Niacin is simply vitamin B3. A vitamin is defined as a nutrient essential to human health that the human body cannot manufacture and must be obtained through ingestion. Many large randomized, double-blind placebo-controlled studies on the effect of niacin and of niacin in combination with a statin for the treatment of high LDL (bad) cholesterol and low levels of HDL (good) cholesterol have been completed to date. A few of the most helpful ones are discussed below. The references for each statement are listed so you can easily look up the study yourself to confirm, at www.ncbi.nlm.nih.gov. This is the Pub Med site of the U.S. National Library of Medicine. Simply copy the reference from this article and paste it into the Pub Med search box and hit your enter or return button. I encourage you to explore the literature further on this important B vitamin.

I’ve been thrilled with the benefits of niacin in my practice but you should be aware of a few caveats if you decide to use niacin.

  1. Like statins, niacin can cause muscle problems. While this is unusual, you should be aware so you can stop niacin if you develop muscle pain while taking it. This is particularly true if you’re taking a statin or another cholesterol-reducing nutrient at the same time.
  2. While the typical dose of niacin provided in a multivitamin ranges from 5 to 25 mg, the dose required to influence cholesterol is at least 400 mg and doses up to 4,000 mg have been used. At these dose levels, like statins, niacin can cause liver irritation and should not be used in people with pre-existing liver disease. Liver enzymes should be checked prior to taking these higher doses of niacin and if any symptoms of liver irritation develop, niacin should be stopped while a blood test for liver enzymes is checked. Such symptoms would include fatigue, yellowing of skin or eyes or darkening of urine. This is unusual and reversible upon stopping niacin but you should be aware.
  3. Niacin can cause “flushing”. Flushing, while harmless, can be quite uncomfortable. It is characterized by redness and tingling (prickly feeling) (some consider this itching) of the skin. Should you notice flushing or tingling of the skin, remember it’s harmless and self-limited. It can be somewhat relieved by getting yourself cooler (removing clothing and/or moving to a cooler area). It can be surprising and cause apprehension but remember, it is harmless and will resolve, usually within 20 minutes to an hour. The good news is that most people build up a tolerance to the flushing over time and then don’t notice it unless they stop their niacin for a while and restart it. If you flush, you can reduce the dose for a few days to build up a tolerance to flushing if necessary. Here is a good routine to minimize flushing with niacin:
  4. Start with a low dose and work up gradually, increasing by one capsule about every 3 weeks. This way you can build up a tolerance to the flushing. In most people, it will stop or become almost unnoticeable over time.
  5. Precede your niacin with aspirin by about 30 minutes. One or two 81 mg aspirin tablets do a great job of preventing flushing if taken about 30 minutes prior to niacin.
  6. Use a delayed-release preparation of niacin to reduce the chance of flushing. Do NOT use “No-Flush” or “Flush-Free” niacin. This product is inositol hexaniacinate – not true niacin and has zero influence on cholesterol! Niacin is nicotinic acid, a completely different compound.
  7. Take your niacin with food or take before bedtime as you might well sleep through any flushing that occurs.
  8. Take the bulk of your daily dose in the evening. Most people seem to flush more with morning dosing than with evening dosing. Also, it can be less convenient to flush during the workday than at home in the evening as the redness may get you some second looks!
  9. If you find yourself flushing regularly, reduce your dose and work back up even more gradually. It is very rewarding become tolerant of the niacin flush, as you should be very pleased with the results of taking niacin.
  10. Finally, if you stop your niacin for several days and start up again, you may have to rebuild your tolerance to the flushing. So use caution by reducing the initial dose and rebuild gradually again, as tolerated.

 

Published Studies on Niacin

Niacin has a beneficial effect on every aspect of the cholesterol profile: it reduces LDL (bad cholesterol), triglycerides and the coronary risk ratio (CRR) (Total Chol/HDL) and raises HDL (good) cholesterol1,2,3,4,5. Niacin also increases the size of the LDL particles, a very important factor in reducing plaque accumulation in arteries3.
In addition, aside from aspirin, niacin is the ONLY compound that consistently reduces the “worst cholesterol”, called “lipoprotein little a” (Lp(a))13,14,15 Lp(a) is discussed in detail below.

In a 2013 study published in the American Journal of Cardiology, data on 407 participants of several previous niacin trials were analyzed to determine niacin’s effect on major cardiovascular events (heart attack, angioplasty or coronary bypass surgery) and coronary disease progression as well as blood glucose levels and diabetes risk. Compared to subjects not on niacin, those on niacin had a greater rise in fasting glucose over three years and a very slightly higher rate of diabetes (not great enough to reach statistical significance) while they enjoyed a whopping 95% reduction in the progression of coronary stenosis (blockage) and over 60% fewer coronary “events” (heart attack, angioplasty or bypass surgery). Clearly, the advantage of niacin far outweighed any disadvantage1.

1

In an article reviewing the evidence behind the therapeutic use of high dose niacin in lowering risk of heart disease, the authors concluded that niacin therapy effectively increases HDL (good) cholesterol, lowers LDL (bad) cholesterol and triglycerides, and increases the size of LDL particles (a good thing which reduces the LDL particle number).  In terms of end results, the authors conclude that niacin “prevents progression and promotes regression of coronary plaque” and reduces cardiovascular illness and death.  They report that combining niacin with statin drugs further improves outcomes2.

2

Oxidative stress is a normal process of life, yet a detrimental one. Not to be confused with emotional stress, oxidative stress promotes biochemical stress and age-related disease. In addition to coronary heart disease, it correlates with risk of Alzheimer’s disease and cancer. We all undergo oxidative stress constantly but it occurs faster in some than others. In people with high levels of LDL (bad) cholesterol and low levels of HDL (good) cholesterol, niacin significantly reduced oxidative stress while it increased HDL and reduced triglycerides3.

3

A review article published in Preventive Cardiology examined previous evidence that niacin enhances the benefits of a statin drug by improving multiple parameters, including LDL, HDL, triglyceride, Lp(a), ApoB (lipoproteins correlating with bad cholesterol), and Apo A1 (lipoproteins correlating with good cholesterol). Evidence demonstrated that adding niacin to a statin drug better reduced the small dense LDL particles (the worst kind) and increased HDL (good) particles as compared to statin drugs alone4.

4

There is a class of prescription medications for cholesterol management called “fibrates”. In a randomized, double-blinded study, niacin improved a number of lipid parameters, including HDL, Lp(a), and the total cholesterol/HDL ratio, better than the fibrate drug gemfibrozil5.

5

How does one decide whether or not to use niacin for cholesterol management? This is both a science and an art. The overall selection of agents must be customized to the individual based on the specific parameters of the lipoprotein profile that need adjustment, the propensity for and experience of side effects, and individual response to therapy. In many individuals, statins alone can optimize the lipoprotein profile because they reduce LDL and slightly raise HDL cholesterol. Niacin is best for reducing triglyceride levels and is more effective than statins in raising HDL cholesterol. For some, therefore, the combination of niacin with a statin may work best. If you personally decide to take niacin I strongly urge you to inform your physician, particularly since statin-related muscle problems are more likely when using both niacin and a statin than with a statin alone. Check your lipoprotein profile before starting niacin and take it consistently. When you have been on your chosen dose consistently for over a month, recheck your lipoproteins to assess the benefit. Be sure to keep your diet and any other cholesterol-influencing medication or supplement constant so you’ll know niacin’s specific contribution.

For people taking a statin already, there are several studies indicating who may benefit from adding niacin and who may not. Niacin was shown to be effective in reducing cardiovascular events (heart attack or need for emergency intervention) in patients with heart disease already taking a statin if the LDL cholesterol was above 70 mg/dl prior to starting niacin6,7. However, in a similar group of patients whose statin had reduced their LDL-cholesterol below 70, niacin did not add any benefit in reducing cardiovascular events despite improving HDL-cholesterol and triglyceride levels. The reason may be that these patients with LDL cholesterol below 70 mg/dl were already achieving the maximum available benefit from their statin alone but those with LDL cholesterol above 70 mg/dl were not. In a diabetic population with cardiovascular disease and already on a statin whose HDL (good) cholesterol was below 40 mg/dl, niacin was shown very effective in reducing cholesterol deposits in artery walls8.

8

I use a combination of a statin with niacin for myself and for many patients in my practice, again based on individual characteristics, and have never seen a serious side effect. That said, my patients are well informed on what to look for and encouraged to report side effects to me. The complication of rhabdomyolysis and death has been reported with the combination of a statin and niacin. The most important issue when using either or both is this: if one feels muscle pain, one must inform their doctor and stop the treatment until able to have a discussion with their doctor.

If you would like to order a slow-release niacin that is less prone to cause flushing, our Cycle-Breakers.com website offers 400 mg. capsules at a fraction of the price of comparable prescription niacin products. Our slow release niacin product is called Duracin. It is carefully tested and manufactured in full compliance of U.S. government Good Manufacturing Processes (GMP). Duracin may be ordered here. Be sure to follow the instructions at the top of this article to minimize flushing. Duracin is less prone to cause flushing. It is not flush-free.

A word about Lp(a) (lipoprotein little a)

Lp(a) is a powerful plaque-forming lipoprotein. It is so destructive that scientists have nicknamed it “the widowmaker” and it is also called “the worst cholesterol”. Lp(a) is genetically determined and is not altered by lifestyle. Therefore, if your level is normal (less than 30 mg/dl or less than 75 nmol/l) on your first measurement, there is no need to measure it again. It will not change significantly. Lp(a) is estimated to be elevated in 15 to 20% of the Caucasian population and can be higher in other races. Elevated levels of Lp(a) is significantly tied to coronary heart disease risk evidenced by a number of clinical trials9,10,11,12. Here’s why your doctor may not have measured this devastating lipoprotein for you: despite the fact that it’s an inexpensive test and that elevated levels are completely treatable, the official recommendation is to measure people for Lp(a) only after they get heart disease or if their LDL cholesterol level is extremely high. In other words, after the gun goes off, check to see if it was loaded. While there is an 85% chance your level is normal, I strongly suggest you request a measurement from your doctor to be sure. It could save your life. Niacin is the single best agent to reduce Lp(a). Lp(a) does not respond to diet, exercise or statin medication. Doses of niacin from 800 mg to 3,000 mg daily may be needed to normalize an elevated Lp(a). An average 77% reduction in Lp(a) was seen over six months in a group of thirty men with elevated Lp(a)13. In a 2002 study of forty-two diabetic patients with elevated levels of Lp(a), a 42% reduction was achieved using niacin14. In another study in 1993, a 36.4% reduction of Lp(a) was seen using 3,000 mg niacin daily15. Again, if you take high dose niacin, you should be under a physician’s care to first be sure your liver function is normal, then to watch for muscle aching. Nausea can also occur at the highest doses of niacin (over 2,500 mg daily).

If you would like to order a slow-release niacin that is less prone to cause flushing, our Cycle-Breakers.com website offers 400 mg. capsules at a fraction of the price of comparable prescription niacin product(s). Our slow release niacin product is called Duracin. It is carefully tested and manufactured in full compliance of U.S. government Good Manufacturing Processes (GMP). Duracin may be ordered here. Be sure to follow the instructions at the top of this article to minimize flushing. Duracin is less prone to cause flushing. It is not flush-free

Red Rice Yeast

Red rice yeast, also referred to as red yeast rice, is a product from the fermentation of rice by the yeast Monascus purpureas.  This product has been used to treat various ailments in Traditional Chinese Medicine for millennia. Red rice yeast is a complex mixture of mevinic acids, sterols, isoflavones, isoflavone glycosides, and monounsaturated fatty acids16,17.

Several studies have indicated that this mixture is capable of lowering LDL cholesterol, total cholesterol, and triglycerides and raising HDL cholesterol18,19,20.  Wide variations of dosage have been used in clinical studies, ranging from 1200mg to 4800mg daily. In one study, the LDL lowering effect of 4800mg of red rice yeast taken each day was found to be equivalent to 20mg of the prescription drug lovastatin taken each day21.

Further, red rice yeast effectively lowers LDL cholesterol and total cholesterol in individuals who are unable to tolerate statin drugs due to muscle pain (myalgias), a side effect of statin drugs.  Red rice yeast did not produce myalgias or elevate indicators of muscle damage in these individuals22.  It is thought that the cholesterol effects of red rice yeast are produced by the combination of synergistic compounds rather than one component alone23.  That said, if you take red rice yeast, you should still be on the alert for muscle pain and report to your doctor if it occurs.

Red rice yeast extract has also been shown to lower C-reactive protein (CRP) a marker of non-specific inflammation in the body and a risk factor for cardiovascular disease24,25,26.

24,25,26

The scientific literature clearly demonstrates that red rice yeast can affect multiple cardiovascular disease risk markers. If you begin red yeast rice, I do recommend you check your cholesterol panel before and 6-8 weeks after starting it to see if it improves. Keep diet and other cholesterol influencing medications or supplements constant so you can isolate the red rice yeast benefit. Also measure your liver enzymes prior to be sure they are normal. If you do notice unusual muscle aching after starting rid rice yeast, you should stop it and consult your physician.

If you’re interested in a reliable source for red yeast rice, carefully tested and manufactured in full compliance of U.S. government Good Manufacturing Processes (GMP), it is available on our website: Cycle-Breakers.com by clicking this link. Cycle-Breakers® Red Rice Yeast is carefully formulated to avoid a toxic byproduct called citrinin, which can contaminate low quality red rice yeast products and may cause kidney damage27. Each capsule of Cycle-Breakers® Red Rice Yeast contains 750mg of red rice yeast (or red yeast rice). Here is a link to the product.

Policosanol

Policosanol is the name for a complex mixture of alcohol compounds (mostly octacosanol) typically derived from sugar cane wax. Policosanol has been evaluated for its potential to improve cholesterol (lipoprotein) levels, reduce the risk of cardiovascular disease, reduce claudication (pain from arterial congestion), and improve cognitive performance.

Policosanol is attractive as a lipid lowering therapy due to its good safety profile and low cost.  Initial studies conducted in Cuba by a policosanol producer revealed excellent efficacy.  Over 6 months, policosanol achieved a 31.2% reduction in LDL cholesterol, a 23.0% in total cholesterol, and a 8.7% increase in HDL cholesterol28.  Several follow up studies also produced impressive results including one lasting two years and showing  a 29.5% reduction in LDL cholesterol, a 21.9% reduction in total cholesterol, a 16.9% reduction in triglycerides, and a 12.4% increase in HDL cholesterol29.

29

Several studies outside of Cuba also demonstrated great results including an Argentinean study showing a 26.7% reduction in LDL cholesterol, a 19.5% reduction in total cholesterol, and a 7.4% increase in HDL cholesterol30. However, other well done studies have found no benefit from policosanol over placebo in regard to cholesterol levels31,32,33. One possible explanation for this discrepancy can be found in the length of the studies.  While there is some overlap between the length of positive and negative studies, positive studies were generally longer (8 weeks to 2 years) while negative studies were generally shorter (6 weeks to 10 weeks).  This suggests that policosanol may be most efficacious with longer treatment periods.  Differences in policosanol quality and composition may also underlie some of this discrepancy. Hopefully ongoing research will elucidate these details more clearly in the near future.  Overall, the cumulative results from numerous studies evaluating the effect of policosanol on cholesterol are quite positive and comparable to older statin drugs, as reviewed in the American Heart Journal in 200234.

34

Several studies suggest that policosanol may also improve intermittent claudication, a painful condition which occurs during walking due to an impaired arterial blood supply to the legs. This pain is analogous to the chest pain (angina pectoris) which occurs when the coronary arteries are impaired. Possibly through its ability to reduce platelet clumping, policosanol improved the symptoms and functional limitations of intermittent claudication more effectively than aspirin and equivalently to an antiplatelet drug (ticlodipine) in randomized and blinded studies35,36.

35,36

Finally, policosanol may improve cognitive function in the domain of reaction time as demonstrated in a population of students and karate athletes37,38.

37,38

Most of these positive studies for cholesterol lowering, claudication therapy, and enhancing reaction time used doses ranging from 10mg to 20mg daily to achieve maximal results.

If you’re interested in a reliable source for policosanol, carefully tested and manufactured in full compliance of U.S. government Good Manufacturing Processes (GMP), it is available on our website, www.cyclebreakers.com.

References
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2Am J Health Syst Pharm. 2003 Jul 1;60(13 Suppl 2):S15-21; quiz S25

3Am J Med Sci. 2013 Mar;345(3):195-9. doi: 10.1097/MAJ.0b013e3182548c28.

4Prev Cardiol. 2003 Fall;6(4):179-88.

5Arch Intern Med. 2000 Apr 24;160(8):1177-84.

6N Engl J Med. 2009 Nov 26;361(22):2113-22. doi: 10.1056/NEJMoa0907569. Epub 2009 Nov 15.

7J Am Coll Cardiol. 2010 Jun 15;55(24):2721-6. doi: 10.1016/j.jacc.2010.03.017.

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9Minerva Med. 1999 May-Jun;90(5-6):151-8.

10Int Angiol. 1996 Mar;15(1):1-5.

11JAMA. 1995 Dec 13;274(22):1771-4.

12J Am Soc Nephrol. 2005 Jun;16(6):1794-802. Epub 2005 Mar 30.

13Kardiologiia. 2011;51(5):9-16.

14Diabetes Obes Metab. 2002 Jul;4(4):255-61.

15Atherosclerosis. 1993 Jun;101(1):61-8.

16Cur Ther Res 1997;58:964-78.

17Am J Clin Nutr 1999;69:231-6.

18Chin Med. 2006 Nov 23;1:4

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20Am J Clin Nutr 1999;69:231-6.

21Am J Cardiol. 2010 Jan 15;105(2):198-204. Epub 2009 Nov 26

22Ann Intern Med. 2009 Jun 16;150(12):830-9, W147-9

23Am J Clin Nutr. 1999 Feb;69(2):231-6.

24Clin Chim Acta. 2005 Feb;352(1-2):217-24.

25Circulation. 2004 Aug 24;110(8):915-20. Epub 2004 Aug 16

26Altern Med Rev. 2001 Jun;6(3):248-71

27J Altern Complement Med 2001;7:133-9.

28Int J Clin Pharmacol Res. 1994;14(1):27-33

29Asia Pac J Clin Nutr. 2004;13 Suppl:S1-176

30Int J Clin Pharmacol Res. 2001;21(1):31-41.

31Am J Clin Nutr. 2006 Dec;84(6):1543-8.

32JAMA. 2006 May 17;295(19):2262-9.

33Complement Ther Med. 2008 Apr;16(2):61-5. Epub 2008 Jan 18.

34Am Heart J. 2002 Feb;143(2):356-65.

35Angiology. 2008 Jun-Jul;59(3):269-77. Epub 2008 Apr 2.

36Angiology. 2004 Jul-Aug;55(4):361-71.

37Neuropsychobiology. 2000;41(3):158-65.

38J Am Coll Nutr. 2009 Aug;28 Suppl:473S-481S.

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