David Leonardi, M.D. ABAAM, CNS

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Statins and Memory Loss

David Leonardi, M.D., ABAAM, CNS

There are numerous case reports of individuals suffering memory loss from statins1,2,3,4,5. One literature review n 2003 summarized 60 case reports of memory loss in statin users6. Sixty cases of memory loss could be classified as rare considering there were about ten million Americans taking statins in 2003. Yet, if you’re taking a statin and feel that it’s causing memory loss, you could be right. Interestingly, however, in every study (clinical trial) I could find, except one, on statins and memory or cognitive function, statins were shown to either slow the rate of age-related cognitive decline or improve cognitive function in subjects who had impairment from an illness or injury7,8,9,10,11,12,13. Three of these were animal studies9,10,11 and the other four were human clinical trials7,8,12,13. In the one study I discovered that showed statin-related cognitive decline beyond just an individual case report, a cardiology clinic reported memory loss in four out of fifty patients studied (8%). This was not proven by cognitive testing but simply by patients claiming memory loss on a questionnaire14. Indeed, statin use is associated with a reduced risk of developing Alzheimer’s disease15, particularly simvastatin, which is one of the few lipid soluble statins that can cross the blood-brain barrier and exert an anti-inflammatory effect on the brain. In a large observational study, simvastatin reduced Alzheimer’s risk by 54% and Parkinson’s disease risk by 49%16.

Why would we see so many case reports of memory loss in statin users when so many clinical studies demonstrated significant brain and cognitive benefits? The most likely explanation is that, aside from identical twins, people are all genetically different from one another. While statins are healthy for the brain in the vast majority of us, some of us may have a particular genetic susceptibility to an aspect of statins that causes memory loss. Certainly that’s the case in regard to muscle pain from statins . If you feel your statin is causing memory loss, what can be done about it?

There is a great deal of published evidence that what statins do to muscle cells is also happening in neurons (brain cells). Because of genetic differences, a minority of us seems to be susceptible to the muscle issue and a much smaller minority to the memory issue. All the evidence thus far points to a reduction in energy production in cells, to which brain and muscle are most susceptible. The reduced energy production, so far, appears related to a relative deficiency on two critical nutrients: Coenzyme Q10 and creatine.

Creatine’s Potential Brain Benefit

Bullet Points:

  • Brain and muscle share the characteristic of variable energy demand, making them very dependent upon creatine for energy.
  • Brain and muscle take up creatine by the same mechanism, shown to be blocked by statins.
  • Because creatine supplementation is effective for statin-associated muscle pain and supplemented creatine does reach the brain, it stands to reason that creatine will also help with statin-related memory loss, although this has not yet been tested in human clinical trials.

Details

Both brain and muscle are very dependent on creatine for adequate energy supply because their demand varies moment to moment according to activity levels (moving and thinking). All cells, including brain cells, ultimately use ATP (created from glucose using the electron transport chain) as an energy source. When the activity of a brain cell is accelerated, it doesn’t contain enough ATP to sustain the higher metabolic rate for very long. At some point early on, all the stored ATP (adenosine tri-phosphate) is depleted into low-energy adenosine di-phosphate (ADP). High-energy phosphate molecules are desperately needed to turn ADP back into ATP to prevent immediate and severe brain cell dysfunction. Of course, our brain cells don’t fail after 6 seconds of intense activity, so we know that they do obtain those phosphate groups to restore ATP. And the source of that phosphate group is creatine17,18. Scientists call this supply line the creatine-phosphate shuttle. When creatine enters the cell it collects a phosphate molecule via an enzyme called creatine kinase (CK) and can transfer (shuttle) that phosphate to ADP when needed to form ATP. You can find more about this on www.Wikipedia.org  or your favorite search engine. Brain cells are fragile and susceptible to insults from oxidative stress and exposure to toxins19. Energy supply is critical to enable brain cells to withstand oxidative and toxic stress and creatine has been shown to be neuroprotective in this regard20,21,22. In fact, studies are now underway investigating whether creatine can be therapeutic for neurodegenerative diseases including Parkinson’s, Alzheimer’s, Amyotrophic Lateral Sclerosis and Huntington’s diseases23,24. Orally supplemented creatine has been shown to be transported into the brain25, to reduce fatigue associated with mental tasks and to increase brain oxygen utilization26. Creatine has already been shown to be beneficial in an animal study of epilepsy27 and in a human clinical trial for depression28. There are numerous documented case reports of statin-associated memory loss and, while not yet proven, it is quite possible that reduced creatine availability to brain cells could be the cause29,30,31,32. No studies have been done yet to determine if statins interfere with creatine transport into brain cells but we already know that they block creatine transport into muscle cells33 and we know the mechanism for creatine transport into brain cells is identical to that for muscle: the sodium-potassium-ATPase pump. This pump, which actively transports creatine into the cell is dependent upon a gradient (unequal distribution) of chloride across the cell membrane. Statins have been shown to upset that gradient, which then reduces creatine transport into the cell. Supplementing creatine has been shown to remedy this problem for the muscle pain34, so it is highly likely that it will also be effective for the memory loss, particularly if used along with CoQ10.

The Advantage of Buffered Creatine

Now, there is an important caveat here. Not all creatine is created equal. When creatine is consumed, before it’s absorbed into our system, much of it is immediately transformed to creatinine (note the extra “in” syllable in creatinine), a waste product of muscle that, when it accumulates, is poisonous. The names are very similar as are their chemical structures but they have a very different effects on the body. Creatine is the energy supply link in muscle cells and creatinine is a waste product that is poisonous at higher levels. When you take standard creatine, such as creatine monohydrate, you lose some of the benefit of the creatine because of its rapid conversion to creatinine and additional strain is placed on the kidneys, required to eliminate that extra creatinine. At the Leonardi Institute, we did a pilot study comparing the effect of standard creatine to a special buffered creatine, designed for maximal absorption into the body with little or no conversion to creatinine. We looked at the blood levels of creatine and creatinine before and after taking standard and buffered creatine. We compared the affect of a daily dose of 9 grams of standard creatine monohydrate to only 3 grams of buffered creatine on blood levels of creatine and creatinine in a crossover trial with a washout period in between. After a week of supplementation, here is what we found.

Creatine Type
Percent increase in
blood creatine per gram ingested per day
Percent increase in
blood creatinine per gram ingested per day
Ordinary14-3.2
Buffered52-8.5

Per gram of product ingested each day, standard creatine monohydrate increased the blood creatine level by 14% while the buffered creatine increased it by 52%, a 3.6-fold difference. Meanwhile, gram for gram, neither the standard creatine monohydrate nor the buffered creatine increased the poisonous blood creatinine level but it dropped by more than double, gram for gram of creatine intake, using the buffered creatine (i.e. buffered creatine had a far more favorable impact). This would imply that, long term, the buffered creatine would be safer.

Clearly, the buffered creatine does more at a lower dose to bring creatine to the muscle and brain cells via the blood stream with no increase in blood level of the potentially harmful creatinine. And there is a very practical advantage: two capsules of buffered creatine can replace seven capsules (or a heaping teaspoon) of creatine monohydrate.

Memory Loss as related to CoQ10

All cells, including brain cells,  contain energy  factories called mitochondria.  It is in the mitochondria where sugar and fats are burned to produce energy in the form of adenosine triphosphate (ATP). Here’s a very simple sequence of how energy is produced from sugar in the mitochondria of our cells. When sugar is broken down, a compound is created called NADH. NADH is loaded with the energy from the sugar and is able to pass on the energy by transferring high-energy electrons down an assembly line of proteins that make up the “electron transport chain”. At each step, energy is extracted from the electrons. One of the key proteins in the electron transport chain is Coenzyme Q (also known as CoQ10). Statins reduce the body’s production of CoQ1034,35,36,37,38. Statin users have up to 40% lower CoQ10 levels in the blood  compared to non-users39. The reason is that CoQ10 is made in the body by the same enzyme that makes cholesterol (HMG CoA reductase) and statins are specifically designed to block this enzyme, which is precisely now they reduce cholesterol40,41,42,43. Since CoQ10 is a critical link in energy production in brain cells and statins deplete us of CoQ10, it’s no surprise that statins could cause memory loss in some genetically susceptible individuals. The obvious solution, then, would simply be to supplement CoQ10. However, it’s not that simple. There is only one clinical study I could find using CoQ10 to treat memory loss in statin users. It was effective in 4 out of 8 patients. The problem with this study is that those patients also stopped their statin medication, causing confusion as to what actually worked: CoQ10 or stopping the statin. Studies on the use of CoQ10 for the treatment of statin muscle pain are mixed. That is, some have shown significant benefit in relieving statin-associated pain,even while continuing their statin44,45,46 and others studies show no benefit47,48. Co Q10 is not the answer for everyone because there are genetic differences among us in regard to exactly where in our biochemistry statins invoke their energy interference within the muscle cell49. Some of us have susceptibility in one aspect of our chemistry and other’s of us in another aspect. That’s why creatine is so important, as discussed above. But even if you find that CoQ10 doesn’t resolve your memory loss, you should be aware of two other reasons to supplement it. First, CoQ10 depletion from statins can cause muscle weakness or discomfort mild enough to be beneath your radar. In other words, you may be weaker than you should be without even realizing it. Second, CoQ10 is critically important for normal function of heart muscle. Low levels of CoQ10 have been linked to a debilitating and dangerous condition called congestive heart failure due to reduced energy production in heart muscle50,51 and CoQ10 has been shown to correct it52,53,54,55. Finally, even in people not using statins, CoQ10 levels decline with age and even this normal depletion compromises heart function56,57. You don’t want to go through life with CoQ10 depletion.

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 simple 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. 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 back and forth 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 brain and muscles while reducing the risk of memory loss and muscle pain 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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