David Leonardi, M.D. ABAAM, CNS

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Statins and Risk of Diabetes

David Leonardi, M.D., ABAAM, CNS

Several studies now point to a clear association between statin use and diabetes risk1,2,3,4. While cause and effect have not been clearly established4, this website is of the opinion that one exists: statins do result in mildly increased insulin resistance (the cause of type II diabetes) and reduced glucose use by cells2,3. While it sounds like a serious problem (and it is), it should not dissuade one from using a statin. There are two reasons for this seemingly brash statement:

1. Statins offer far greater benefit in reducing coronary heart disease risk than the detriment they pose by increasing diabetes risk, but more importantly,

2. There is a fully logical explanation for the increased risk of diabetes with statins and I believe it is 100% reversible. I will explain below.

First let me back up statement number 1 above. In a large meta-analysis involving over 71,000 participants on statin treatment, it was estimated that statins resulted in one new case of diabetes per 255 patients treated over 4 years while they simultaneously saved 5.4 lives from fatal heart attacks5. That’s 5.4 lives saved from fatal heart disease for every 1 new case of diabetes incurred. And diabetes is a preventable disease! As risk factors go, statins are near the bottom of the list. At the very top are: obesity and overweight, sedentary lifestyle, and high-glycemic nutrition. All of these are completely within your control and mine. With optimal weight control, a low-glycemic nutrition plan and exercise, one should be able to take a statin with impunity regarding diabetes.

Now let’s examine statement 2 above. Evidence is rapidly emerging on exactly now statins increase the risk of diabetes. Here is the relatively simple explanation.

All of our cells burn glucose (sugar) to produce ATP (energy). Critical to this process are two important nutrients: Coenzyme Q10, a key protein that orchestrates energy production in cells, and creatine, another protein that acts as a storage depot for the raw material of energy supply. Statins affect both of these proteins very significantly.

CoQ10. Statins deplete CoQ10 levels in the body6,7,8,9. Since CoQ10 is required for energy production, people who are low in CoQ10 produce less energy in their cells. If you’d like more details on how CoQ10 produces ATP, click on this article: The Role of CoQ10 in Cellular Energy Production. Remember, the raw material for energy production is glucose (sugar), so as we produce less energy we use less glucose. With less use of glucose, our cells naturally take up less glucose from the blood. This was proven in a 2013 study by Ganeson and Ito at Oregon State Universtity10. Reduced uptake of glucose by the roughly 100 trillion cells in the human body has a substantial impact on blood sugar – it rises! As blood sugar rises, we require more insulin to be made by the pancreas. A vicious cycle ensues. Higher insulin, in turn, leads to insulin resistance11, resulting in even higher insulin levels, which causes even more insulin resistance, the cause of type II diabetes. Therefore, supplementing CoQ10 when taking statins is critically important for the prevention of diabetes (not to mention preventing congestive heart failure, muscle pain and weakness, memory loss and fatigue). But before you start supplementing CoQ10, read about the importance of creatine below.

Creatine. Statins also block the flow of creatine into muscle cells12. Creatine provides an energy storage depot and delivery system for phosphate, a key molecule for energy supply in cells. Very simply, here’s how it works in muscle cells, our highest users of energy. Creatine enters the cell and attaches to a phosphate molecule to make creatine-phosphate. We store lots of creatine-phosphate in muscle cells. Within seconds of muscle contraction, the cell depletes its energy stores. That is, all of its ATP (adenosine TRI-phosphate) is diminished to ADP (adenosine DI-phosphate). ADP is useless in supplying energy. It must have that 3rd phosphate group and become ATP to provide energy. Creatine-phosphate immediately comes to the rescue by donating its phosphate molecule to ADP, quickly restoring ATP and allowing continued muscle contraction. This is all basic biochemistry taught in all schools. You can read about it on www.Wikipedia.org. Just search “creatine phosphate”. The gist is that reduced creatine in cells has the same impact as reduced CoQ10 – reduced availability and use of energy. As cells use less energy, they need less glucose and therefore remove less glucose from the blood. Multiply this by 100 trillion cells, and blood glucose rises, requiring more insulin and promoting that vicious cycle of insulin resistance, moving us closer to type II diabetes. Many of these findings are very recent as of this writing (September, 2013). As a result, no studies have yet been done on real people to prove that creatine and CoQ10 together can prevent diabetes in people taking statins. Personally, I’m convinced of it for two reasons:

1. Enough studies have been done to demonstrate that low CoQ10 from statins causes insulin resistance and supplementing CoQ10 prevents the insulin resistance.

2. There are several studies showing that creatine reduces blood sugar in diabetics – much better than placebo13 and as effectively as two well-known diabetes medications14,15.

Clearly, studies are needed to examine the relationship among statins, diabetes risk, CoQ10 and creatine. We know that supplementing creatine and CoQ10 can guard against statin-related muscle problems such as pain, weakness, soreness and cramps. For details and evidence on this, click here. And to date, we have very good evidence that creatine and CoQ10 will also prevent the increase in diabetes risk from statin use by improving energy production and therefore, glucose utilization in cells. If you would like to take a combination of CoQ10 and creatine along with vitamin D3 in the easiest and most effective combination available, I invite you to visit our Statin Sidekick page.

Why Vitamin D3? Vitamin D3 is included in Statin Sidekick because of its association with optimal muscle function and the prevention of muscle pain16,17,18, it’s success in clinical trials of statin users19,20, and the overwhelming prevalence of insufficient vitamin D levels in the U.S. and other developed countries21,22,23. For more on this topic, please click on this article: Vitamin D Supplementation as a Possible Solution to Statin-Related Muscle Pain.

But aside from that important benefit, the data showing vitamin D improves glycemic control is enormous. In these seven published clinical trials, higher levels of vitamin D were associated with better glycemic control and reduced risk of type II diabetes24,25,26,27,28,29,30.

In a meta-analysis of 21 prospective studies involving over 76,000 subjects done at Harvard University, those in the highest category of vitamin D status had a 38% lower risk of diabetes than those in the lowest category31. 38% reduced risk will save a lot of people from diabetes, given how common this disease is today. Vitamin D clearly deserves a place in Statin Sidekick.

The Safest, Most Economical and Simplest Solution

As a result of the overwhelming benefits of both CoQ10 and buffered creatine we’ve discussed, along with the benefit of vitamin D3 in those with insufficient levels, I decided to combine CoQ10, buffered creatine and vitamin D3 into one convenient nutritional supplement called Statin Sidekick™. I believe Statin Sidekick is critically important for anyone taking a statin medication along with anyone physically active and interested in insuring a steady supply of energy to muscle and brain cells along with optimal blood sugar control. Two capsules of Statin Sidekick provides a proprietary blend of buffered creatine and CoQ10 totaling 1,500 mg. along with 2,000 iu of vitamin D3. These three ingredients are included in the most optimal ratio based on published clinical trials, our original research and our patient experience at the Leonardi Institute. The recommended dose is 2 to 3 capsules twice a day (always with food) for the first week (called a “loading dose”) followed by 1 to 2 capsules twice a day thereafter. There appears to be a benefit in stopping your statin for the first week while taking the loading dose of Statin Sidekick but we don’t recommend this without first checking with your practitioner.

If you notice muscle aching that you feel is related to your statin while taking Statin Sidekick™, simply increase the dose back up to 3 capsules twice a day. Of course, you should also notify your physician that your statin is causing you pain. You may adjust the dose of Statin Sidekick up and down to see what dose you personally require to eliminate statin-related muscle aching while optimizing muscle energy availability and performance. In unusual circumstances, a few people may even require 4 capsules twice a day. Detailed dosing instructions are included with each order. If 4 capsules of Statin Sidekick twice daily doesn’t relieve your statin side effects, the next logical step might be to discuss with your practitioner, either an alternative statin or a lower dose of the same statin while continuing Statin Sidekick. If you’re unsuccessful with that approach you may want to discuss statin alternatives with your practitioner.

Statin Sidekick is an essential nutrient for anyone taking a statin. It provides that margin of safety and peace of mind that you’re getting the best possible performance from your muscles while reducing the risk of muscle pain and muscle dysfunction that can accompany statin use. If you would like to order Statin Sidekick, it is available on our Cycle-Breakers.com website by clicking here. Statin Sidekick is carefully tested and manufactured in full compliance of U.S. government Good Manufacturing Processes (GMP).

Statin Sidekick Supplement Facts

Serving size 2 capsules

Servings per Container 30 (60 capsules)

Active Ingredients
Amount per Serving
% DRV
Vitamin D32,000 iu500
A proprietary blend of Kre-Alkalyn® (buffered creatine) and Coenzyme Q101500 mgDRV not established

Directions: Take 2-3 capsules twice daily WITH FOOD (within 45 minutes of a meal). You may reduce the dose after the first week if you remain free of statin side effects, or increase the dose if needed.

References
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1J Am Coll Cardiol. 2013 Jan 8;61(1):44-53. doi: 10.1016/j.jacc.2012.09.036. Simvastatin effects on skeletal muscle: relation to decreased mitochondrial function and glucose intolerance.

 

2Cancer Biol Ther. 2013 Feb;14(2):92-4. doi: 10.4161/cbt.23290. Epub 2012 Dec 19. Statins impair glucose uptake in tumor cells.

 

3J Am Coll Cardiol. 2013 Jan 15;61(2):148-52. doi: 10.1016/j.jacc.2012.09.042. Epub 2012 Dec 5. Cardiovascular event reduction versus new-onset diabetes during atorvastatin therapy: effect of baseline risk factors for diabetes.

 

4Cleve Clin J Med. 2012 Dec;79(12):883-93. doi: 10.3949/ccjm.79a.12091. Statins and diabetes risk: fact, fiction, and clinical implications.

 

5Lancet 2010; 375:735–742. Statins and risk of incident dia- betes: a collaborative meta-analysis of randomised statin trials.

 

6J Clin Pharmacol. 1993 Mar;33(3):226-9. Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study.

 

7Mol Aspects Med. 1997;18 Suppl:S137-44. Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors.

 

8Arzneimittelforschung. 1999 Apr;49(4):324-9. Effect of treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on serum coenzyme Q10 in diabetic patients.

 

9J Atheroscler Thromb. 2005;12(2):111-9. Reduction of serum ubiquinol-10 and ubiquinone-10 levels by atorvastatin in hypercholesterolemic patients.

 

10Metab Syndr Relat Disord. 2013 Aug;11(4):251-5. doi: 10.1089/met.2012.0177. Epub 2013 Mar 15. Coenzyme Q10 Ameliorates the Reduction in GLUT4 Transporter Expression Induced by Simvastatin in 3T3-L1 Adipocytes.

 

11Diabetes. 2013 Aug;62(8):2905-16. doi: 10.2337/db12-1463. Epub 2013 Mar 25.
Carotid body denervation prevents the development of insulin resistance and hypertension induced by hypercaloric diets.

 

12Circulation. 2006;114:II_288. Lipid and Lipoprotein Metabolism: Clinical V Abstract 1495: Serum Creatine/Creatinine Ratio Elevation and Statin Myalgia

 

13Med Sci Sports Exerc. 2011 May;43(5):770-8. doi: 10.1249/MSS.0b013e3181fcee7d.
Creatine in type 2 diabetes: a randomized, double-blind, placebo-controlled trial.

 

14Wien Med Wochenschr. 2011 Nov;161(21-22):519-23. doi: 10.1007/s10354-011-0905-7. Epub 2011 Jul 29. Comparison of antihyperglycemic effects of creatine and glibenclamide in type II diabetic patients.

 

15Med Sci Sports Exerc. 2011 May;43(5):770-8. doi: 10.1249/MSS.0b013e3181fcee7d. Creatine in type 2 diabetes: a randomized, double-blind, placebo-controlled trial.

 

16Endocr Rev 1986; 7:434-48. Role of vitamin D in skeletal muscle function.

 

17N Engl J Med 2007; 357:266-81. Vitamin D Deficiency.

 

18Mol Aspects Med 2008; 29:407-14. Vitamin D and skeletal muscle tissue and function.

 

19Dermatoendocrinol. 2010 Apr;2(2):77-84. doi: 10.4161/derm.2.2.13509. The role of vitamin D and SLCO1B1*5 gene polymorphism in statin-associated myalgias.

 

 

20Transl Res. 2009 Jan;153(1):11-6. doi: 10.1016/j.trsl.2008.11.002. Epub 2008 Dec 6. Low serum 25 (OH) vitamin D levels (<32 ng/mL) are associated with reversible myositis-myalgia in statin-treated patients.

 

21Am J Med 2002; 112:659-62. Vitamin D insufficiency among free-living healthy young adults.

 

22Nutr Rev 2003; 61:107- 13. Prevalence of vitamin D insufficiency in Canada and the United States: importance to health status and efficacy of current food fortification and dietary supplement use.

 

23J Nutr 2005; 135:310-6. Vitamin D intake: a global perspective of current status.

 

24Br J Nutr. 2011 May 17:1-6. [Epub ahead of print] Diabetes prevalence is associated with serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in US middle-aged Caucasian men and women: a cross-sectional analysis within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

 

25Eur J Clin Nutr. 2011 Jul 6. doi: 10.1038/ejcn.2011.68. [Epub ahead of print]
An estimate of the global reduction in mortality rates through doubling vitamin D levels.

 

26J Nutr. 2011 Jun 22. [Epub ahead of print] Low Serum Vitamin D Is Associated with High Risk of Diabetes in Korean Adults.

 

27Appl Physiol Nutr Metab. 2011 Apr;36(2):264-70. Serum 25OH vitamin D level, femur length, and risk of type 2 diabetes among adults.

 

28Scand J Clin Lab Invest. 2011 Apr 26. [Epub ahead of print] Serum 25-hydroxyvitamin D levels are inversely associated with glycated haemoglobin (HbA(1c)). The Tromsø Study.

 

29Diabetes Care. 2011 Jun;34(6):1284-8. Epub 2011 Apr 22. Vitamin d status in relation to glucose metabolism and type 2 diabetes in septuagenarians.

 

30Med J Aust. 2011 Apr 4;194(7):334-7. Serum 25-hydroxyvitamin D and glycated haemoglobin levels in women with gestational diabetes mellitus.

 

31Diabetes Care. 2013 May;36(5):1422-8. doi: 10.2337/dc12-0962. Blood 25-hydroxy vitamin D levels and incident type 2 diabetes: a meta-analysis of prospective studies.

 

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