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Inflammation, statins, and cardiovascular disease: Is D the missing link?

Posted on: February 19, 2013   by  John Cannell, MD


Oxidative stress is thought to underlie cardiovascular and many other diseases. Oxidative stress reflects an imbalance between the byproducts of humans being on fire (oxidizing), and human’s ability to readily repair that damage with our antioxidant systems. Malondialdehyde (MDA) is a complex molecule that serves as a marker for oxidative stress, the higher the MDA, the worse the oxidative stress.

Inflammation (Latin root “to set alight or burn”) is a complex biological response to harmful stimuli, such as pathogens, damaged cells, toxins, or antigens. Inflammation is an attempt by the organism to remove the injurious stimuli and begin the healing process. C-reactive protein (CRP) is a protein found in the blood, the levels of which rise in response to inflammation: the higher the CRP, the worse the inflammation.

Both statins and vitamin D have pleiotropic effects, meaning they have many different effects on the body and appear to work in different ways. Pleiotropic comes from the Greek, meaning “more,” and “convert.” While the mechanism of action of vitamin D’s pleiotropy is easy to explain (vitamin D has as many mechanisms of action as genes it regulates), the same cannot be said of statins. How do they work other than reducing cholesterol?

Dr Thozhukat Sathyapalan and colleagues of the Hull York Medical School in England recently conducted a remarkable study of two statins.

Sathyapalan T, Shepherd J, Atkin SL, Kilpatrick ES. The effect of atorvastatin and simvastatin on vitamin D, oxidative stress and inflammatory marker concentrations in patients with type 2 diabetes: a crossover study. Diabetes Obes Metab. 2013 Jan 28.

The two statin drugs studied were atorvastatin (Lipitor) and simvastatin (Zocor). Both lower cholesterol equally well and both are used to prevent cardiovascular disease. However, at least one study shows that cardiovascular events are lower with atorvastatin than simvastatin.

Jacobson TA, Wertz DA, Hoy T, Kuznik A, Grochulski D, Cziraky M. Comparison of cardiovascular event rates in patients without cardiovascular disease in whom atorvastatin or simvastatin was newly initiated. Mayo Clin Proc. 2008 Dec;83(12):1316-25.

That is, Lipitor may work better than Zocor in preventing cardiovascular disease. Is that because Lipitor reduces oxidative stress and inflammation better than Zocor? Remember, both drugs lower cholesterol equally well. If Lipitor works better at lowering inflammation and oxidative stress than Zocor does, what is Lipitor’s mechanism of action? We know that statins as a group elevate vitamin D levels.

Wilding PM. Cardiovascular disease, statins and vitamin D. Br J Nurs. 2012 Feb 23-Mar 7;21(4):214-20. Review.

However, Dr Sathyapalan wanted to find out if Lipitor increased vitamin D levels more than Zocor, and if so, was that elevation associated with better CRP and MDA levels. So he studied lipid levels, 25(OH)D levels, markers of inflammation (CRP) and a marker of oxidative stress (MDA) in 26 patients taking one or the other drug. He then did a cross-over study.

After 3 months on one statin, lipids, CRP, 25OHD and MDA were measured repeatedly. The patient’s statin was then switched and the same procedure was then followed after taking the other statin. LDL cholesterol concentrations were similar whether the same patients took Zocor or Lipitor. However, the mean 25OHD was higher and both the CRP and MDA concentrations lower while on Lipitor compared to Zocor.

Furthermore, the average 25OHD was higher after Lipitor than Zocor. What’s more, the changes in 25OHD predicted the changes in CRP (p=0.002) and MDA (p=0.001) levels. Thus, compared to Zocor, Lipitor demonstrates more beneficial effects in raising 25OHD levels, and Lipitor lowers markers of oxidative stress and inflammation better than Zocor.

Is that why Lipitor works better than Zocor, because it raises vitamin D levels higher?

The authors wrote,

“In conclusion, 25OHD concentrations are higher in patients when taking atorvastatin rather than simvastatin at doses that lead to equivalent reductions in LDL. The vitamin D rise is associated with significant improvements in markers of oxidative stress and inflammation suggesting this may be a mechanism by which atorvastatin, in particular, exerts its pleiotropic effects.”

18 Responses to Inflammation, statins, and cardiovascular disease: Is D the missing link?

  1. Karsten

    So then, controlling for the impact of statins on the level of vitamin D, do statins have any impact on CVD? Or are they just a very roundabout way to cause liver damage?

  2. [email protected]

    And dementia, memory loss, impotens, diabetes, all kind om joint pain, muscle weekness and pain to rabdomyolysis, the list of damages and sideeffects from statins can be lifelong.

    Besides, cholesterol is essential. The best way to lower the oxidativ stress in the body is to eat less carbohydrates, especially fructose an HFCS, skip the short sugars.

  3. Rita and Misty


    I appreciate your thoughts on cholesterol, and diet.

    Perhaps you know something about NALD?

    A recent ultrasound of mine, taken due to a kidney stone attack, indicated that my liver is slightly swollen…my HMO is telling me NALD…. My total cholesterol is only 156. My fasting glucose is typically under 90. I am underweight. I run (at least) 6 miles, every single day of the week. I haven’t touched sugar, especially, especially HFCS, in years. And for the last 6 months I’ve followed a Paleo diet (with few transgressions).

    I’m at a loss.

    The liver is a pretty necessary organ.

    I am certainly attached to mine, and would like to heal it.


  4. Rita and Misty

    Regarding my above post…I certainly didn’t mean to limit replies to @eelisabethpuur.

    I will consider any knowledge out there on NALD.

    I’m certainly frightened to learn about my sick liver. Especially as I try to be so health conscious. And, I really don’t have a knowledgeable physician (imo).

    The liver is an essential organ–in everyone’s opinion.

  5. pab

    rita and misty, since you are already paleo….this may not apply, but, try the diet for celiac disease. It is understood that NALD can be related to that.

  6. [email protected]

    To Rita and Misty
    Regarding NALD – have found lecithin granules /choline supplements to help. And the four key nutrients that I’ve seen clear up so many liver problems are Alpha Lipoic Acid, N-Acetyl-Cysteine, Selenium, and Milk Thistle. Artichokes are a liver-friendly food. And beware if you are on any meds/otc. Patrick

  7. Dan

    So Vitamin D is the real benefit, once again. Everyone I know that went on a Statin eventually developed memory problems. No surprise since Cholesterol makes up 70% of the brain.

    Exercise is stress so doing excessive exercise while liver under stress is counterproductive.

    Reishi Mushroom Extract can can liver repair per studies.

  8. Rita and Misty

    Thanks, Patrick!

    I take all of the supplements you mentioned…except for artichokes.

    I was Vitamin D deficient for years. Really, my 25(OH)D level has only been corrected since the latter half of 2011.

    I lost a tremendous amount of weight upon correction of my d level.

    I lost 30% of my total body weight within 6 weeks..with no change to diet or exercise.

    Perhaps this weight loss has taxed my liver?

    I feel awesome. I’m not tired. I can run 6 miles up and down hill without effort.

    I take my physical health to be a good sign.

    Regarding kidney stone/liver connection…I continue to alkalize my body with magnesium and potassium.

    We shall see what my future holds….

    Again, thank you kindly for your reply.


  9. Doctorsh

    @rita and misty
    Get yourself checked for iron overload, hemochromatosis and other liver disorders. An ultrasound is only a picture. Pictures don’t indicate function.

  10. [email protected]

    @Rita and Misty Hi,

    I know only a little about this kind of NALD (Neonatal adrenoleukodystrophy (NALD) is a disorder that is a member of a family of disorders that result from defects in the biogenesis and/or functioning of the peroxisomes and are referred to as peroxisome biogenesis disorders, PBDs. NALD belongs to the Zellweger spectrum PBDs which includes Zellweger syndrome and infantile Refsum disease (IRD). Zellweger syndrome represents the extreme of the clinical manifestation of peroxisome biogenesis dysfunction with patients rarely surviving their first year of life. Zellweger syndrome is associated with either severe, moderate or mild defects in all peroxisome functions. An additional phenotypic spectrum in PBDs is represented by rhizomelic chondrodysplasia punctata, RCDP. RCDP is distinguished from the Zellweger spectrum PBDs by manifesting with more severe skeletal involvement as well as specific biochemical characteristics.)

    Is it that NALD you mean?

    If you want to be nice to your liver, you can eat raw red beets. Now I am not sure of the English words, maybe it is “cheese grater” to “grate” the beets? It is know since old times that raw beets and spinach is good for the liver. Also I can that raw ginger, also grated? don´t know the right word and turmeric powder, Remember that turmeric needs some dairy, creame, creme fraiche … some dairy, to be optimal anti-inflammatory. I also agree to Samoapat´s recommendations.

  11. Rita and Misty

    @doctorsh–thanks…hope I can do these tests on my own…and I do not have an accommodating physician. Long story, with an unhappy ending for me (currently).

    @[email protected]–Thanks for your kind reply. I am being told I (potentially) have non alcoholic fatty liver disease…a metabolic condition (I think).

    It’s amazing…I work so hard at maintaining health…this has simply thrown me for a loop.

    I feel absolutely wonderful…I am in good weight…I have endurance…
    (I think for now I will simply choose to put this ultra sound out of my mind–what’s the worst thing that could happen?)

  12. Rita and Misty

    @pab–thank you for your response as well re: celiac disease… I’m open to looking at all options w/in my control.

  13. Richard Barkley

    @Rita and Misty – Loosing 30% of your body weight in 6 weeks is astounding and may help explain your liver problems. As you may know, but haven’t thought of, your fat is where most of the toxins that your body can’t get rid of (mostly through the liver) are stored. When you loose weight, they are released into circulation and the liver has to deal with them.

  14. Rita and Misty

    @Richard Barkley,

    Thank you for your helpful post. Yes, the thought of toxins in my liver had crossed my mind.


    Back in the fall of 2011, I raised my Vitamin D level from what had typically been around 32 ng/ml to a healthier reading of 75 ng/ml…. and within 6 weeks my weight dropped from 130 lbs to 105 lbs. I am small framed at 5’2″.


    I’ve always been fanatical regarding diet and exercise; however, my hormones became unbalanced at age 40, and I was also borderline hypo at a reading of 3.8….I trudged along grumpy and plump until 2011 (age 46).

    I keep my 25(OH)D level at around 100 ng/ml now.

    I feel great.

    BTW–I think my HMO would like to “blame” my inflamed liver on my Vitamin D level.

    Isn’t that absolutely crazy?

    (you never know how unlucky you are until you are without a competent physician…just ask me)

  15. [email protected]

    @Rita and Misty

    I should have known that NALD, we say it exactly the same way in Swedish. Read the article, modified corn starch is everywhere. NALD is caused by carbs, especially HFCS. Did you sheck your thyroide again? sometimes the hypo becomes a hyper, it would explain yout weight loss in six weaks.

    Experts agree – sugar truly is a health destroyer. And whether it’s real sugar or sugar in the form of high-fructose corn syrup, negative health effects will surely pop up wHFCSith over-consumption. But some research does indeed pinpoint HFCS specifically for causing a concerning amount of damage. Two studies coming to these conclusions found evidence showing that HFCS promotes obesity and causes damage to the liver.
    One study, conducted by Duke University
    researchers, found that HFCS leads to scarring of the liver, similar to liver disease. Some research has said that HFCS scars the liver as bad as excessive alcohol consumption. Other research also found that it worsens the condition of those with non-alcoholic fatty liver disease (NAFLD).Researchers looked at more than 400 patients with NAFLD and asked them questions about their HFCS consumption, specifically in beverages sweetened with the sweet stuff (like sodas). Those who consumed the greatest amount of HFCS had the most severe scarring of their livers.
    another study, researchers found the link between HFCS and obesity was more pronounced than that of sucrose and obesity. The experiment was done on rats, one group of which was fed a solution of sugar and another with HFCS. The group fed HFCS gained “significantly” more weight than the others. Then, they monitored changes in rats who ate rat chow compared with those who supplemented their rat chow with a HFCS solution—those with the HFCS gained about 48% more weight than those without.

    Read more:

  16. Rita and Misty

    @[email protected]

    Gracias for your response….

    Calmly speaking, I understand fully that an ultrasound is simply a picture. I am being told that my “picture” indicates slight scarring of the liver. Calmly speaking: who knows? this might be very old scarring….

    I haven’t touched HFCS in years..nor simple sugars.

    Yes, I have been known to indulge in carbs…but not for the last 6 months…

    I’ve tightened up my diet even more..and am focusing on high protein, low calorie items.

    Again, I feel absolutely awesome…my energy level and endurance are peak.

    I think for now I will do the “ostrich pose” on this issue…. 🙂

    Thanks for mentioning hyperthyroidism…but, I’m not hyperthyroid (at least by old-fashioned temperature monitoring).

    I’d like to take some space to say a BIG THANK YOU to everyone who has kindly responded to my concerns….

    The liver is a pretty necessary organ…I will heed as much of the above advice as possible. Unfortunately, regarding requesting tests, I am at the mercy of a bureaucratic HMO….I plan to do the tests I can do on my own… 🙂

  17. boston

    check out reconnectivetherapy.com
    i’ve been using this therapy (happily) for many years –and have seen miracles with my friends and family on it too—
    [email protected]

  18. [email protected]

    What can the mechanism be for statins raising VitD-level? Where does the vitamin D come from in this case?? Siri Dyvik

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