Should Niacin Replace All Statins?

Cardiovascular disease is becoming more prevalent every year. In fact, each year 1 in every 4 deaths is attributed to cardiovascular disease.(1) For many years now, statins have been the drug of choice when it came to doctors trying to control this disease progression. While diet and exercise should of course be used as a primary means of improving the lipid profile, many doctors find that compliance from the patient can be an issue, and sometimes the numbers will not get into optimal ranges even with a change in diet and/or lifestyle. This is why most doctors turn to statins as a way to control cholesterol levels.

However, not only do statins have side effects that niacin does not, but niacin has actually always been shown to be MORE effective than statins at actually reducing the chance of dying from a cardiovascular event. Yet, niacin has a benign side effect of making the patient “flush”, which is one of the main reasons that it is not utilized more often.

My purpose for this article is to inform about the differences between statins and niacin, go over some relevant research, and give the reader an educated understanding of how to properly use niacin to improve their own lipid profile.

What’s so bad about statins?

While widely utilized, statins are known to have a host of negative side effects:

• Muscle pain, muscle cramps, or weakness (quite common, and if combined with intense exercise, can rarely lead to rhabdomyolysis [excessive breakdown of muscle tissue] or kidney failure for some)(2)
  • These muscle pain symptoms tend to occur in 1 – 25% of the people taking statins.
• Possible decrease in exercise performance (2)
• Increased risk of hypothyroidism (3)
• Increased risk of diabetes / obesity for some, and depending on the statin (3)
• Increase in negative side effects with polypharmacy (i.e. taking another pharmaceutical drug besides a statin at the same time) (3)
• Associated with neuropsychiatric issues (irritability, homicidal impulses, threats to others, road rage, depression and violence, paranoia, alienation, antisocial behaviour) (4)
• Associated with cognitive and memory impairments (4) and possible increased risk of dementia, although can decrease dementia risk in some cases if the dementia stems from vascular issues (5), a benefit that is shared by niacin (without the risk).
• Associated with sleep disturbances (4)
• Associated with sexual dysfunction (4)
• Possible liver dysfunction (6)
• Possible increase in risk of cataracts (6)

One thing that I want to point out right away is that anyone taking a traditional statin should also be taking CoQ10 or Ubiquinol. Statins are known to deplete CoQ10 in the cells, which is one of (but not the only) the main reasons that they are associated with a host of side effects, especially ones that are related to muscle pain.(7) This human study I’m referencing used 50mg of CoQ10 twice a day and found very beneficial effects at preventing muscle-related side effects from statins.

Besides CoQ10 depletion, most of the other side effects of statins come from their forceful suppression of cholesterol synthesis. I won’t get into the ins-and-outs of cholesterol and the lipoproteins (LDL, HDL, etc.) in this article, but I do want to make it clear that cholesterol is a very important molecule in our body that serves a variety of functions including membrane fluidity, immune system function (8, 9), nutrient absorption, reproductive biology, stress responses, salt and water balance, and calcium metabolism.(10)

Cholesterol is also used to repair or “patch up” arteries after they have been damaged, by oxidative stress for example. However, this process is very intricate and involves chronic inflammation, macrophages (which become something called “foam cells”), and oxLDL.(11) However, when cholesterol levels get too high, there can be an increase in foam cell production, which is a hallmark of the initial stages of atherosclerosis.

The original cholesterol-lowering “drug”: Niacin

Niacin was actually the first very successful “drug” or nutraceutical used to restore balance to the lipid profile back in 1955.(12)  Since then, pharmaceutical companies have been trying to find other drug options to use instead of niacin. Why would they do that? Well, niacin cannot be patented, so the amount of money that can be gained from using it is negligible. Also, many doctors and patients either do not understand what the niacin flush is or that it will go away after a week or so of continuous use. Lastly, there have been some reports about niacin causing liver enzymes to rise (we will discuss this more in depth in a few minutes), and the combination of niacin with a statin does not lead to better outcomes than either alone (which makes many doctors opt for the statin).

This last point is particularly important, as all of the recent headlines talking about how “dangerous” niacin is are referring to one of the studies in which niacin was *added* to a statin vs. the statin alone. The combination had increased side effects.(16) However, there has never been a study showing that a statin on its own worked better than niacin on its own.

Moreover, there is evidence that statins do not reduce sudden cardiac death or all-cause-mortality (17), whereas niacin does (18).

Niacin has been successfully used to improve the lipid profile (decrease LDL, increase HDL, lower triglycerides, etc.) for decades.(13) Niacin also has the added benefit of increasing HDL, which the vast majority of the statins do not, which not only helps to protect vasculature, but also is very beneficial to brain and nervous system health, can help preserve cognitive function in disease states, and has “a wide range of other functions including anti-oxidation, anti-inflammation, pro-endothelial function, anti-thrombosis, and modulation of immune function.”(14) This is important because besides exercise, niacin is one of the only ways to powerfully raise HDL levels in addition to lowering LDL and triglycerides.

Why isn’t niacin utilized more often?

The main reasons that doctors choose to not use niacin (besides a lack of familiarity with the nutrient) is that niacin can have some side effects, and this tends to deter the physicians and patients away from it. However, proper understanding of niacin can mitigate these side effects while keeping all of the benefits.

The main side effect is flushing. This happens whenever someone first starts taking niacin, and it can be uncomfortable for some. There are two ways to deal with the flushing. You can either start with a low dose (like 100 mg X 3 a day with food) and gradually increase the dose by 50-100mg per dose. This will lessen the initial flush, making it more tolerable, but it will prolong the total amount of time that you will flush for (a couple weeks instead of a few days). The other way is to start with the full dose (the average dose is 1g X 3 a day with food) on the weekend or when you will not have to deal with a lot of people seeing you. This will give you an intense flush for the first day or two, after which the flush will greatly lessen. Usually the flush will be gone, or nearly gone, by the end of the week. Even if you do still feel some slight tingling after this time, it will not be enough for anyone to notice.

The next main side effect is a rise in liver enzymes. This generally only occurs with time-released niacin (i.e. Niaspan).(23) This is why I prefer to use regular niacin. Time-released is used to lessen the flush. This becomes a non-issue with regular niacin though, as long as you get over the first week and do not miss a dose. In general, all of the side effects of niacin are greater with the time-released version. The rise in liver enzymes occurs, like most of the side effects we will be discussing, due to methyl group depletion. I won’t go into the intricacies of methyl groups in this article, but just know that when you are lacking in methyl groups, it can make it harder for the liver to function correctly. However, there is an easy solution to this problem: just supplement with methyl groups! You can easily do this by taking the same amount of trimethylglycine (or “betaine”, but do NOT use “betaine HCl”) with the niacin.(15, 20, 21, 22) That is, if you take 3g of niacin total each day, then just take 3g of trimethylglycine in the morning. [For those who wish to be extra cautious, a small amount of daily vitamin b6 can be taken with niacin to further prevent any negative liver side effects. The b6 also helps to boost methylation.](24)

The last main side effect from niacin is a small rise in blood sugar. For most people, even with the time-released version, the increase is so small that it doesn’t really matter. However, this risk again can likely be mitigated by taking trimethylglycine (TMG) every day while you take niacin at the same dose (see above). This is because the decrease in methyl groups can alter skeletal muscle membrane composition that can lead to insulin resistance. Taking TMG will likely mitigate this.

All of this may seem more troublesome than just taking a daily statin, and it is, but it is worth it. Taking niacin in this fashion has been shown to reduce the number of heart attacks (24%), strokes (26%), cardiovascular surgery (46%), and deaths (11%, adding a mean of 1.63 years of life to men 30-65 years old with one or more preceding heart attacks).(19)

Lastly, while statins tend to have a host of negative side effects, niacin actually has a plethora of “side benefits”. Going over each benefit would be too long for this article, but I will be posting future articles addressing these benefits on this page. Stay tuned!

For further information about niacin, “Niacin, The Real Story” by Hoffer et. al. is a fantastic book explaining the many uses and benefits of niacin therapy for a variety of conditions. These were the doctors who have been personally using niacin for decades since the 1950’s. (If you decide to order the book using the above link, I will receive a small commission with no extra charge to you, and you will be supporting this site!)

References

1. CDC, NCHS. Underlying Cause of Death 1999-2013 on CDC WONDER Online Database, released 2015. Data are from the Multiple Cause of Death Files, 1999-2013, as compiled from data provided by the 57 vital statistics jurisdictions through the Vital Statistics Cooperative Program. Accessed Feb. 3, 2015.
2. Parker BA, Thompson PD. Effect of Statins on Skeletal Muscle: Exercise, Myopathy, and Muscle Outcomes. Exercise and sport sciences reviews. 2012;40(4):188-194. doi:10.1097/JES.0b013e31826c169e.
3. Ramkumar S, Raghunath A, Raghunath S. Statin Therapy: Review of Safety and Potential Side Effects . Acta Cardiologica Sinica. 2016;32(6):631-639. doi:10.6515/ACS20160611A.
4. Tuccori M, Montagnani S, Mantarro S, Capogrosso-Sansone A, Ruggiero E,
   Saporiti A, Antonioli L, Fornai M, Blandizzi C. Neuropsychiatric adverse events
   associated with statins: epidemiology, pathophysiology, prevention and
   management. CNS Drugs. 2014 Mar;28(3):249-72. doi: 10.1007/s40263-013-0135-1.
   Review. PubMed PMID: 24435290.
5. Schultz BG, Patten DK, Berlau DJ. The role of statins in both cognitive impairment and protection against dementia: a tale of two mechanisms. Translational Neurodegeneration. 2018;7:5. doi:10.1186/s40035-018-0110-3.
6. Dimmitt SB, Stampfer HG, Warren JB. Common statin side effects explain poor compliance. British Journal of Clinical Pharmacology. 2015;80(1):170-171. doi:10.1111/bcp.12594.
7. Skarlovnik A, Janić M, Lunder M, Turk M, Šabovič M. Coenzyme Q10 Supplementation Decreases Statin-Related Mild-to-Moderate Muscle Symptoms: A Randomized Clinical Study. Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2014;20:2183-2188. doi:10.12659/MSM.890777.
8. Jia Wang, Zhong-xin Hong. Cholesterol Supplement can Alleviate the Severity of Pulmonary Infection of Patients with Hypocholesterolemia. Journal of Food and Nutrition Research. Vol. 4, No. 3, 2016, pp 131-136. http://pubs.sciepub.com/jfnr/4/3/1
9. Míguez MJ, Lewis JE, Bryant VE, et al. Low cholesterol? Don’t brag yet … hypocholesterolemia blunts HAART effectiveness: a longitudinal study. Journal of the International AIDS Society. 2010;13:25. doi:10.1186/1758-2652-13-25.
10. Tabas I. Cholesterol in health and disease. The Journal of Clinical Investigation. 2002;110(5):583-590. doi:10.1172/JCI16381.
11. Chistiakov DA, Bobryshev YV, Orekhov AN. Macrophage‐mediated cholesterol handling in atherosclerosis. Journal of Cellular and Molecular Medicine. 2016;20(1):17-28. doi:10.1111/jcmm.12689.
12. https://academic.oup.com/nutritionreviews/article-abstract/15/5/137/2671245?redirectedFrom=PDF
13. Goldberg AC. Clinical trial experience with extended-release niacin (Niaspan):
    dose-escalation study. Am J Cardiol. 1998 Dec 17;82(12A):35U-38U; discussion
    39U-41U. PubMed PMID: 9915661.
14. Hottman DA, Chernick D, Cheng S, Wang Z, Li L. HDL and Cognition in Neurodegenerative Disorders. Neurobiology of disease. 2014;72PA:22-36. doi:10.1016/j.nbd.2014.07.015.
15. Co-administration of equimolar doses of betaine may alleviate the hepatotoxic risk associated with niacin therapy. https://www.sciencedirect.com/science/article/pii/S0306987799910113
16. Effects of Extended-Release Niacin with Laropiprant in High-Risk Patients. https://www.nejm.org/doi/full/10.1056/NEJMoa1300955
17. Al-Gobari M, Le H-H, Fall M, Gueyffier F, Burnand B. No benefits of statins for sudden cardiac death prevention in patients with heart failure and reduced ejection fraction: A meta-analysis of randomized controlled trials. Abete P, ed. PLoS ONE. 2017;12(2):e0171168. doi:10.1371/journal.pone.0171168.
18. Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, Friedewald
    W. Fifteen year mortality in Coronary Drug Project patients: long-term benefit
    with niacin. J Am Coll Cardiol. 1986 Dec;8(6):1245-55. PubMed PMID: 3782631.
19. Clofibrate and Niacin in Coronary Heart Disease. JAMA. 1975;231(4):360–381. doi:10.1001/jama.1975.03240160024021
20. ApSimon MM, Rawling JM, Kirkland JB. Nicotinamide megadosing increases hepatic
    poly(ADP-ribose) levels in choline-deficient rats. J Nutr. 1995
    Jul;125(7):1826-32. PubMed PMID: 7616297.
21. Muscle Creatine Content in Rats Given Repeated Large Doses of Nicotinamide: Effects of Dietary Methionine, Choline, Carnitine, and Other Supplements. https://academic.oup.com/jn/article-abstract/116/12/2409/4763247?redirectedFrom=fulltext
22. Hepatic Content of S-Adenosylmethionine, S-Adenosylhomocysteine and Glutathione in Rats Receiving Treatments Modulating Methyl Donor Availability. https://academic.oup.com/jn/article-abstract/119/10/1478/4738907?redirectedFrom=PDF
23. McKenney JM, Proctor JD, Harris S, Chinchili VM. A comparison of the efficacy
    and toxic effects of sustained- vs immediate-release niacin in
    hypercholesterolemic patients. JAMA. 1994 Mar 2;271(9):672-7. PubMed PMID:
    8309029.
24. Basu TK, Mann S. Vitamin B-6 normalizes the altered sulfur amino acid status
    of rats fed diets containing pharmacological levels of niacin without reducing
    niacin’s hypolipidemic effects. J Nutr. 1997 Jan;127(1):117-21. PubMed PMID:
    9040554.