Statins reduce spirochetal burden/modulate immune responses in mouse model of LD

Topics with information and discussion about published studies related to Lyme disease and other tick-borne diseases.
Posts: 2758
Joined: Thu 1 Jul 2010 8:33

Statins reduce spirochetal burden/modulate immune responses in mouse model of LD

Postby RitaA » Sat 26 Mar 2016 17:29

Microbes Infect. 2016 Mar 16. pii: S1286-4579(16)00050-2. doi: 10.1016/j.micinf.2016.03.004. [Epub ahead of print]

Statins reduce spirochetal burden and modulate immune responses in the C3H/HeN mouse model of Lyme disease.

Van Laar TA1, Hole C1, Rajasekhar Karna SL1, Miller CL1, Reddick R2, Wormley FL1, Seshu J3.

Author information

1 South Texas Center for Emerging Infectious Diseases, Center for Excellence in Infection Genomics and Department of Biology, The University of Texas at San Antonio, San Antonio, TX 78249, USA.
2 The Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78249, USA.
3 South Texas Center for Emerging Infectious Diseases, Center for Excellence in Infection Genomics and Department of Biology, The University of Texas at San Antonio, San Antonio, TX 78249, USA.


Lyme disease (LD) is a systemic disorder caused by Borrelia burgdorferi. Lyme spirochetes encode for a functional 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR EC serving as a rate limiting enzyme of the mevalonate pathway that contribute to components critical for cell wall biogenesis. Statins have been shown to inhibit B. burgdorferi in vitro. Using a mouse model of Lyme disease, we found that statins contribute to reducing bacterial burden and altering the murine immune response to favor clearance of spirochetes.

Copyright © 2016. Published by Elsevier Masson SAS.


Borrelia burgdorferi; Cell wall biogenesis; Lyme disease; Statins

PMID: 26993029 [PubMed - as supplied by publisher]

Edited to update to direct link to the Rel-Risk blog entry: ... et-al.html

Thursday, March 24, 2016

Notes from:
Van Laar TA, et al. Statins reduce spirochetal burden and modulate immune responses in the C3H/HeN mouse model of Lyme disease. Microbes Infect. 2016 Mar 15.

Sequence analysis of the borrelial genome indicates the presence of homologs of the mevalonate pathway (MP) leading to the synthesis of isopentenyl-5-pyrophosphate (IPP). IPP is an essential component of several isoprenoids and a precursor for peptidoglycan synthesis contributing to the structural integrity of several organisms.

Previous studies from our laboratory have shown that B. burgdorferi possesses a functional MP. The rate-limiting step of the MP is the reduction of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) to mevalonate by HMG-CoA reductase (HMGR). We also determined that B. burgdorferi has a functional HMGR and that enzyme activity could be inhibited using two commercially available HMGR inhibitors (statins). Though the mevalonate pathway is found in many genera of bacteria known to cause human disease, including Staphylococcus, Streptococcus, Listeria, and Borrelia, the potential antimicrobial use of statins has not been fully explored.

The inhibitory property of stains has several implications for interactions of B. burgdorferi with its hosts. As our in vitro data showed that statins were able to exert an inhibitory effect on B. burgdorferi, we wanted to test the effects of statins on a susceptible C3H/HeN [mouse] model of Lyme disease.

Though we have previously found that statins are able to inhibit survival of B. burgdorferi in vitro, the levels of statins in the blood of treated animals do not reach the concentrations necessary for complete bactericidal effects in vitro. However, the numbers of bacteria reaching distal tissues are significantly lower in statin-treated mice, providing evidence that even some bactericidal activity can have an impact on the course of a borrelial infection.

Statins have also been previously shown to negatively affect bacterial growth and survival, even in bacteria that do not encode an hmgr homolog due to their cholesterol lowering properties. Bacteria which require host cholesterol have defects in growth when cholesterol levels are lowered. As B. burgdorferi absolutely require cholesterol for their outer membranes, it is likely that the lowered levels of cholesterol would provide less cholesterol for B. burgdorferi to sequester, thus preventing B. burgdorferi from properly forming its membrane.

It appears that statin treatment contributes to decreased bacterial burden in infected mice, which could be due to either direct interference with spirochetal growth or by limiting available cholesterol to the bacteria. Moreover, it is also possible that alterations in the immune response to the spirochetes could lead to increased bacterial clearance. It is interesting to speculate that statins could potentially have a number of as yet uncharacterized primary or secondary anti-borrelial effects.

[Time to buy stock in statins before Lyme activists discover this paper. So do more people not taking statins contract overt LD than do people on a regular regimen of statins? Is that a beneficial side-effect for people living in LD endemic areas?]
Last edited by RitaA on Tue 29 Mar 2016 20:06, edited 1 time in total.

Posts: 2758
Joined: Thu 1 Jul 2010 8:33

Re: Statins reduce spirochetal burden/modulate immune responses in mouse model of LD

Postby RitaA » Sun 27 Mar 2016 1:59

Member dlf posted this previously in another thread, but I think it might be worthwhile including it here as well:

Proc Natl Acad Sci U S A. 2015 Apr 28; 112(17): 5491–5496.
Published online 2015 Apr 13. doi: 10.1073/pnas.1502561112PMCID: PMC4418910

Hypercholesterolemia and ApoE deficiency result in severe infection with Lyme disease and relapsing-fever Borrelia

Alvaro Toledo,a Javier D. Monzón,a James L. Coleman,a,b Juan C. Garcia-Monco,a and Jorge L. Benacha,1

a Department of Molecular Genetics and Microbiology and
b New York State Department of Health, Center for Infectious Diseases, Stony Brook University, Stony Brook, NY, 11794

Edited by Yasuko Rikihisa, The Ohio State University, Columbus, OH, and approved March 20, 2015 (received for review February 9, 2015)


Elevated levels of cholesterol and other lipid abnormalities are common diseases of adults. Cholesterol is an essential nutrient for Borrelia. To test whether increased levels of cholesterol could affect the infection with Borrelia, we used two types of mice with different deficiencies in cholesterol transport that result in increased cholesterol levels and infected them with two species of Borrelia. Infection with the agent of Lyme disease resulted in higher severity, increased number of bacteria in the joints, and ankle swelling. The higher mortality found in infections with relapsing-fever Borrelia was associated with an apolipoprotein E deficiency and was independent of cholesterol levels. Elevated serum lipids are common diseases that could be a risk factor for increased severity in Lyme disease.

Keywords: cholesterol, Lyme disease, relapsing fever, Borrelia, tick-borne


The Lyme disease (Borrelia burgdorferi) and relapsing-fever (Borrelia hispanica) agents have distinct infection courses, but both require cholesterol for growth. They acquire cholesterol from the environment and process it to form cholesterol glycolipids that are incorporated onto their membranes. To determine whether higher levels of serum cholesterol could enhance the organ burdens of B. burgdorferi and the spirochetemia of B. hispanica in laboratory mice, apolipoprotein E (apoE)-deficient and low-density lipoprotein receptor (LDLR)-deficient mice that produce large amounts of serum cholesterol were infected with both spirochetes. Both apoE- and LDLR-deficient mice infected with B. burgdorferi had an increased number of spirochetes in the joints and inflamed ankles compared with the infected wild-type (WT) mice, suggesting that mutations in cholesterol transport that result in high serum cholesterol levels can affect the pathogenicity of B. burgdorferi. In contrast, elevated serum cholesterol did not lead to an increase in the spirochetemia of B. hispanica. In the LDLR-deficient mice, the course of infection was indistinguishable from the WT mice. However, infection of apoE-deficient mice with B. hispanica resulted in a longer spirochetemia and increased mortality. Together, these results argue for the apoE deficiency, and not hypercholesterolemia, as the cause for the increased severity with B. hispanica. Serum hyperlipidemias are common human diseases that could be a risk factor for increased severity in Lyme disease.

Posts: 2758
Joined: Thu 1 Jul 2010 8:33

Re: Statins reduce spirochetal burden/modulate immune responses in mouse model of LD

Postby RitaA » Sun 27 Mar 2016 16:46

While obesity may not always result in higher cholesterol levels, the relationship between diet-induced obesity and dissemination of Lyme disease is one area that Toronto-based researcher Tara Moriarty and her team are investigating: ... iarty-tara

Tara Moriarty BA, BSc, PhD

Research location: University of Toronto - St. George Campus (downtown)

Primary Research Area: Infectious Diseases & Immunopathology

Secondary Research Area: Molecular & Cell Biology

Research Statement:
Blood-borne dissemination of pathogens is responsible for most of the mortality associated with bacterial infections, but dissemination mechanisms remain largely uncharacterized. We investigate the dissemination mechanisms of invasive bacteria (especially the Lyme disease spirochete Borrelia burgdorferi), in an effort to develop alternative therapeutic approaches for treating bacterial infection.


... 3) Roles of chemotaxis and motility in Borrelia dissemination; 4) Role of diet-induced obesity in enhanced host susceptibility to disseminated Lyme disease;


... my major current research goal is to ensure timely publication of the projects we are currently executing.

Edited to add:


4. Role of diet-induced obesity in enhanced host susceptibility to disseminated Lyme disease

Lyme disease is the most common vector-borne disease in the northern hemisphere, and its incidence is increasing rapidly throughout the industrialized world (nearly a three-fold increase over the last twenty years). Although climate warming and associated expansion of tick habitat are thought to contribute to increasing Lyme disease incidence, the reasons for the rising prevalence of this disease are not yet fully understood. Increasing Lyme disease incidence has occurred in parallel with rising rates of obesity in the industrialized world. One of the major groups affected by Lyme disease is the middle-aged, in whom obesity and associated conditions such as diabetes and cardiovascular disease are now widely prevalent. We recently found that high fat diet-induced obesity in mice is associated with a significantly elevated bacterial burden in many tissues to which Borrelia disseminates. Currently, we are investigating the mechanisms responsible for enhanced Borrelia infectivity in obese hosts, and are examining the effects of hyperglycemia and systemic vascular inflammation to disseminated Lyme disease.


Posts: 2758
Joined: Thu 1 Jul 2010 8:33

Re: Statins reduce spirochetal burden/modulate immune responses in mouse model of LD

Postby RitaA » Sun 27 Mar 2016 20:23 ... at.1003109


Lipid Exchange between Borrelia burgdorferi and Host Cells

Jameson T. Crowley , Alvaro M. Toledo , Timothy J. LaRocca , James L. Coleman , Erwin London , Jorge L. Benach

Published: January 10, 2013 DOI: 10.1371/journal.ppat.1003109


Borrelia burgdorferi, the agent of Lyme disease, has cholesterol and cholesterol-glycolipids that are essential for bacterial fitness, are antigenic, and could be important in mediating interactions with cells of the eukaryotic host. We show that the spirochetes can acquire cholesterol from plasma membranes of epithelial cells. In addition, through fluorescent and confocal microscopy combined with biochemical approaches, we demonstrated that B. burgdorferi labeled with the fluorescent cholesterol analog BODIPY-cholesterol or 3H-labeled cholesterol transfer both cholesterol and cholesterol-glycolipids to HeLa cells. The transfer occurs through two different mechanisms, by direct contact between the bacteria and eukaryotic cell and/or through release of outer membrane vesicles. Thus, two-way lipid exchange between spirochetes and host cells can occur. This lipid exchange could be an important process that contributes to the pathogenesis of Lyme disease.

[The full article follows.]



Through the use of fluorescent and radiolabeled cholesterol, we showed that a lipid exchange between spirochetes and host cells can occur. Two main conclusions can be derived from our studies. First, we show that when B. burgdorferi come in direct contact with epithelial cells the spirochetes can extract cholesterol from epithelial cell membranes. Second, both cholesterol and the antigenic cholesterol-glycolipids of B. burgdorferi are transferred to epithelial cells through direct contact between the spirochete and the plasma membrane and through released OMV.

As an extracellular pathogen, nutrient acquisition from the immediate environment is an essential process for B. burgdorferi to be able to persist in the host. Here we provide evidence that B. burgdorferi can extract cholesterol, an essential membrane lipid, from eukaryotic cells. We demonstrated that B. burgdorferi attach to epithelial cells and can incorporate cholesterol directly from the plasma membrane. Using fluorescence microscopy, B. burgdorferi were shown to attach to epithelial cells and associate with BODIPY-cholesterol labeled regions of the plasma membrane. Evidence that the spirochetes extract cholesterol from epithelial cells comes from confocal microscopy images which showed colocalization of the BODIPY-cholesterol from the HeLa cells and the lipoprotein OspB at the point of attachment, and also the presence of BODIPY-cholesterol throughout the spirochete which extended away from the cell. Cholesterol acquisition has been shown to also be an important process for extracellular pathogens.


Given the limited biosynthetic capabilities of B. burgdorferi to make cholesterol and other important lipids, the process of cholesterol extraction from host cells is likely to be more biologically significant for the nutrition of the spirochetes early in infection as nutrient acquisition is crucial for the replication of the bacteria. Once the bacteria have disseminated and an infection has been established, it is likely that even at low levels, the transfer of antigenic lipids from the spirochete to host cells becomes more significant. Whether inserted directly into the plasma membrane of eukaryotic cells, or attached to the surface of these cells, the presence of foreign antigens with similar composition and structural characteristics could have multiple consequences for the host immune response. It is also possible that these transferred lipids could contribute to heightened inflammation and arthritis. Furthermore, if the immune response were to recognize cells with transferred lipid antigens, the cells themselves become targets of immune effectors.

The last sentence certainly sounds like an interesting avenue for Lyme disease researchers to pursue. Are transferred lipid antigens contributing to a persistent immune response (as opposed to a persistent infection) in some (but not all) cases where people continue to experience symptoms despite antibiotic treatment?

Posts: 294
Joined: Sun 7 Apr 2013 15:36

Re: Statins reduce spirochetal burden/modulate immune responses in mouse model of LD

Postby dlf » Sun 27 Mar 2016 21:56

Statin medications are currently portrayed by the medical community (and pharmaceutical companies) as being extremely beneficial and relatively benign. However, there can be some very serious side effects and consequences associated with their use.

Consider the following studies and links as cautionary warnings as to why it may not be a particularly good idea to use them for all Lyme patients, (especially patients with neuroborreliosis).

McFarland AJ, Anoopkumar-Dukie S, Arora DS, et al. Molecular Mechanisms Underlying the Effects of Statins in the Central Nervous System. Harry GJ, ed. International Journal of Molecular Sciences. 2014;15(11):20607-20637. doi:10.3390/ijms151120607.

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly referred to as statins, are widely used in the treatment of dyslipidaemia, in addition to providing primary and secondary prevention against cardiovascular disease and stroke. Statins’ effects on the central nervous system (CNS), particularly on cognition and neurological disorders such as stroke and multiple sclerosis, have received increasing attention in recent years, both within the scientific community and in the media. Current understanding of statins’ effects is limited by a lack of mechanism-based studies, as well as the assumption that all statins have the same pharmacological effect in the central nervous system. This review aims to provide an updated discussion on the molecular mechanisms contributing to statins’ possible effects on cognitive function, neurodegenerative disease, and various neurological disorders such as stroke, epilepsy, depression and CNS cancers. Additionally, the pharmacokinetic differences between statins and how these may result in statin-specific neurological effects are also discussed.

Are statins really wonder drugs?
Grover, Harpreet Singh et al.
Journal of the Formosan Medical Association , Volume 113 , Issue 12 , 892 - 898

Statins [3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase], are wonder drugs that have reshaped the treatment of hypercholesterolemia and associated cardiovascular diseases. However, evidence from various studies indicates existence of many statin-induced side effects such as myopathies, rhabdomyolysis, hepatotoxicity, peripheral neuropathy, impaired myocardial contractility, diabetes, autoimmune diseases, and erectile dysfunction (ED). Physician awareness of these side effects is reported to be very low even for the adverse effects (AEs) most widely reported by patients. This can lead to incorrect treatment decisions, compromised patient care, and an increase in patient morbidity. Therefore, the aim of this article is to highlight the AEs of statin therapy as well as rational management of these complications to further improve safety of these excellent drugs.

Miron VE, Zehntner SP, Kuhlmann T, et al. Statin Therapy Inhibits Remyelination in the Central Nervous System. The American Journal of Pathology. 2009;174(5):1880-1890. doi:10.2353/ajpath.2009.080947.

Remyelination of lesions in the central nervous system contributes to neural repair following clinical relapses in multiple sclerosis. Remyelination is initiated by recruitment and differentiation of oligodendrocyte progenitor cells (OPCs) into myelinating oligodendrocytes. Simvastatin, a blood-brain barrier-permeable statin in multiple sclerosis clinical trials, has been shown to impact the in vitro processes that have been implicated in remyelination. Animals were fed a cuprizone-supplemented diet for 6 weeks to induce localized demyelination in the corpus callosum; subsequent return to normal diet for 3 weeks stimulated remyelination. Simvastatin was injected intraperitoneally during the period of coincident demyelination and OPC maturation (weeks 4 to 6), throughout the entire period of OPC responses (weeks 4 to 9), or during the remyelination-only phase (weeks 7 to 9). Simvastatin treatment (weeks 4 to 6) caused a decrease in myelin load and both Olig2strong and Nkx2.2strong OPC numbers. Simvastatin treatment (weeks 4 to 9 and 7 to 9) caused a decrease in myelin load, which was correlated with a reduction in Nkx2.2strong OPCs and an increase in Olig2strong cells, suggesting that OPCs were maintained in an immature state (Olig2strong/Nkx2.2weak). NogoA+ oligodendrocyte numbers were decreased during all simvastatin treatment regimens. Our findings suggest that simvastatin inhibits central nervous system remyelination by blocking progenitor differentiation, indicating the need to monitor effects of systemic immunotherapies that can access the central nervous system on brain tissue-repair processes.

Negative Impact of Statins on Oligodendrocytes and Myelin Formation In Vitro and In Vivo
Steve Klopfleisch1,*, Doron Merkler2,*, Matthias Schmitz1, Sabine Klöppner1, Mariann Schedensack2, Gunnar Jeserich4, Hans H. Althaus1, and Wolfgang Brück2,3

Statins are widely prescribed drugs in cardiovascular diseases. Recent studies also demonstrated anti-inflammatory and immunomodulatory properties of statins by modulating the activity of small GTPases. Statins are thus considered as potential therapeutic drug for the inflammatory demyelinating disease multiple sclerosis (MS). However, little is known about the effects of statins on myelin-forming oligodendrocytes. Here, we show that statins hamper process and myelin formation in vitro by interfering with Ras and Rho signaling in mature oligodendrocytes and provide evidence that statins impair ongoing remyelination in vivo. Our findings may have significant implications for the application of statins in MS patients and in other demyelinating diseases of the CNS.

<snip from conclusion>

In this context, our study indicates that statins should be used carefully since long-term application may negatively influence the intrinsic remyelinating capacity, not only in MS patients, but also in other demyelinating diseases of the CNS.

Lancet Neurol. 2011 Aug;10(8):691-701. doi: 10.1016/S1474-4422(11)70144-2.
Simvastatin as add-on therapy to interferon β-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4 trial.
Sorensen PS1, Lycke J, Erälinna JP, Edland A, Wu X, Frederiksen JL, Oturai A, Malmeström C, Stenager E, Sellebjerg F, Sondergaard HB; SIMCOMBIN study investigators.


Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partly effective. We aimed to establish whether add-on of simvastatin, a statin with anti-inflammatory properties, improves this efficacy.

We enrolled treatment-naive patients with relapsing-remitting multiple sclerosis in a multicentre, placebo-controlled, double-blind, randomised, parallel-group trial of simvastatin (80 mg daily) as add-on treatment to intramuscular interferon beta-1a (30 μg weekly). After starting treatment with interferon beta, patients were randomly assigned (in computer-generated blocks of four patients) to simvastatin 80 mg per day or placebo for 1-3 years. Patients and treating and evaluating physicians were masked to treatment allocation. The primary outcome measure was annual rate of documented relapses; analysis was by intention to treat. This trial is registered at, NCT00492765.

We randomly assigned 307 patients to interferon beta plus simvastatin (n=151) or plus placebo (n=156). Annual rate of documented relapses was 0·19 (95% CI 0·13 to 0·28) in the simvastatin group and 0·14 (95% CI 0·09 to 0·23) in the placebo group (absolute difference 0·059, 95% CI -0·21 to 0·09; p=0·35). Time to first documented relapse (20th percentile) was 18·1 months in patients on simvastatin and 21·5 months in those on placebo (hazard ratio 1·21, 95% CI 0·74 to 1·99; p=0·51). Mean number of new or enlarging T2 lesions was 2·96 in the simvastatin group and 2·52 in the placebo group (ratio of new lesions, 1·17, 95% CI 8·89 to 1·55; p=0·25). Eight (6%) patients on simvastatin and 17 (13%) on placebo had no disease activity (odds ratio 0·42, 95% CI 0·17 to 1·00; p=0·05). No unexpected adverse events were seen. Generally, adverse events were mild and there were no group differences in infections or musculoskeletal disorders, including myalgia (five [3%] patients on simvastatin and nine [6%] on placebo). Rhabdomyolysis and myoglobinuria were not reported and there were no differences in serum creatine phosphokinase.

We found no beneficial effect of simvastatin as add-on therapy to interferon beta-1a. Although unlikely, we can not exclude that combination of other statins with other disease-modifying drugs still could be beneficial.

For this last study, the interpretation looks like it was written to minimize reporting any poor outcomes. From the findings section, the patients taking the statin medication had more annual relapses, more rapid first time relapses, more new or enlarging T2 lesions and fewer patients with no increased disease activity than the placebo cohort. Sounds to me like the study should have reported that patients taking statin medications had statistically poorer outcomes than those who didn't and that statin use might be contraindicated for patients with multiple sclerosis.

Posts: 2758
Joined: Thu 1 Jul 2010 8:33

Re: Statins reduce spirochetal burden/modulate immune responses in mouse model of LD

Postby RitaA » Sun 27 Mar 2016 22:22

dlf wrote:Statin medications are currently portrayed by the medical community (and pharmaceutical companies) as being extremely beneficial and relatively benign. However, there can be some very serious side effects and consequences associated with their use.

Consider the following studies and links as cautionary warnings as to why it may not be a particularly good idea to use them for all Lyme patients, (especially patients with neuroborreliosis).

I was just doing a quick tour of the internet to see what I could find regarding Cholestyramine (CSM) ("a resin which has been historically used for lowering cholesterol levels”), that is sometimes prescribed by doctors who limit their practice to the treatment of Lyme disease. While some Lyme disease patients do report improvement while taking this cholesterol-lowering prescription medication, others do not. I have yet to see any published research to support the routine use of any cholesterol-lowering medication (including statins) in humans with Lyme disease at this point in time.

I would definitely not start (or recommend) taking any statin on the off-chance that it might prevent the dissemination of Lyme disease. There are simply too many unknowns/risks/side effects associated with statins from what I've seen and heard. Here is just one example that comes to mind: ... edication/

It's Not Dementia, It's Your Heart Medication: Cholesterol Drugs and Memory

Why cholesterol drugs might affect memory

By Melinda Wenner Moyer on September 1, 2010

Cholesterol-lowering statins such as Lipitor, Crestor and Zocor are the most widely prescribed medications in the world, and they are credited with saving the lives of many heart disease patients. But recently a small number of users have voiced concerns that the drugs elicit unexpected cognitive side effects, such as memory loss, fuzzy thinking and learning difficulties. Hundreds of people have registered complaints with MedWatch, the U.S. Food and Drug Administration’s adverse drug reaction database, but few studies have been done and the results are inconclusive. Nevertheless, many experts are starting to believe that a small percentage of the population is at risk, and they are calling for increased public awareness of the possible cognitive side effects of statins—symptoms that may be misdiagnosed as dementia in the aging patients who take them.


Vulnerable Genes?

Many experts agree that for most people the risk is quite low, but they are beginning to believe the effects are real. “A subset of the population is vulnerable,” argues Joe Graedon, co-founder of the consumer advocacy Web site the People’s Pharmacy, which has collected hundreds of reports of cognitive-related statin side effects in the past decade. Some researchers believe these people have a genetic profile that puts them at risk.


Edited to add:

Please note that I’m not personally recommending any of the following, however here is a list of alternatives to statins in case anyone else was also wondering about this: ... ternatives

Statin Alternatives

There are many non-statin medications your doctor might prescribe:

- Bile acid-binding resins, like cholestyramine (Prevalite, Questran) and colesevelam (Welchol), remove cholesterol-rich bile acids, important for digestion, from your intestines. Your body then pulls cholesterol out of your blood to make more of them, which brings your numbers down.

- Fibrates such as clofibrate (Atromid-S), fenofibrate (Antara, Fenoglide, Lipofen), and gemfibrozil (Lopid) mostly help your heart by reducing the amount of blood fat (called triglycerides) and raising “good” HDL levels.

- Niacin, a B vitamin, affects how your body makes blood fats and can also lower LDL.

- Ezetimibe (Zetia) lowers the amount of cholesterol your intestines absorb. A recent study suggests that “on top of statins, adding ezetimibe further lowers LDL and the risk of heart attack or stroke,” Cannon says.

- Omega-3s are found in fatty fish like mackerel, trout, herring, sardines, albacore tuna, and salmon. You can also get them in supplements and medication. You mainly take them to lower triglycerides.

- PCSK9 inhibitors help clear cholesterol from your blood. They “have been developed for people who are not at their goal cholesterol despite current treatments,” Cannon says. The FDA has approved two of these drugs: alirocumab (Praluent) and evolocumab (Repatha). It’s not clear yet how these meds affect a person’s risk for heart attack and stroke.

New Drugs on the Way

Scientists also are researching new types of medicines that can bring down cholesterol. None of them are available yet, but possibilities include:

- ETC-1002 works inside the liver to change how the body uses cholesterol and fats.

- CETP inhibitors such as anacetrapib and evacetrapib raise HDL and lower LDL. Previous studies found that these drugs didn't work well or even increased heart risks, but scientists are now looking at more promising versions.

Posts: 2758
Joined: Thu 1 Jul 2010 8:33

Re: Statins reduce spirochetal burden/modulate immune responses in mouse model of LD

Postby RitaA » Mon 28 Mar 2016 6:52

My apologies for drifting somewhat off topic, however I found this archived webpage from Ohio State University that mentions a correlation between bacteria levels and cholesterol levels in mice for another tick-borne disease:


(Last updated 7/2/07)

COLUMBUS , Ohio – People who have high cholesterol levels may be much more susceptible to a particular disease transmitted by the bites of ticks, a new study in mice suggests.

Scientists infected mice with Anaplasma phagocytophilum, the bacterium that causes human granulocytic anaplasmosis (HGA), a disease with flu-like symptoms. Bacteria levels were 10 times greater in mice that were genetically predisposed to high cholesterol levels and that were also fed a high-cholesterol diet.

The results confirmed what the researchers had suspected – that A. phagocytophilum depends on its host's cholesterol stores for its survival.

The implication is that the higher a person's cholesterol levels, the more susceptible that person may be to developing a severe case of HGA, said Yasuko Rikihisa, the study's lead author and a professor of veterinary biosciences at Ohio State University.

Yet HGA is difficult to accurately diagnose, as symptoms are similar to those of the flu and include high fever, muscle aches, chills and headaches. But in some cases misdiagnosis can be devastating.

“Young, healthy people probably don't develop very severe symptoms,” Rikihisa said. “But left undetected, the infection could kill an older person or someone with a weakened immune system.”

She added that immune function slowly declines and blood cholesterol levels typically increase as we age.

The researchers report their findings in a recent issue of the Journal of Infectious Diseases. Rikihisa conducted the study with Qingming Xiong and Xueqi Wang, both graduate students in Rikihisa's laboratory.

Experts say that HGA is on the rise in the United States , where anywhere from 400 to more than 1,000 people contract the disease each year. It is transmitted by the bite of Ixodes scapularis, or deer tick. Deer ticks also spread Lyme disease, and are found primarily in the upper Midwest, New England, parts of the mid-Atlantic States and northern California.

The disease attacks immune cells called granulocytes, which the body normally uses to destroy infectious pathogens.

In the current study, Rikihisa and her colleagues studied two groups of mice. Animals in one group lacked a protein important for maintaining normal blood cholesterol levels, while mice in the other group had this protein, called apoliprotein E (apoE).

For about a month several mice from each group ate a diet high in cholesterol, while the rest of the animals ate a diet with normal cholesterol levels. At the end of the month, some of the mice from each feeding group were infected with A. phagocytophilum.

Ten days after infecting the mice, the researchers collected blood samples from each mouse and also harvested each animal's spleen and liver. They determined the extent of the infection based on the amount of bacteria found in each tissue. Since the spleen and liver both filter blood, and the liver makes and stores cholesterol, the researchers thought that they may find higher concentrations of bacteria in these organs.

A. phagocytophilum levels were 10 times higher in mice predisposed to high blood cholesterol levels and that ate the high-cholesterol diet than in any other group of mice, including the animals that were predisposed and ate a normal-cholesterol diet.

Bacterium levels were highest in the blood and the spleen, and were quite low in the liver of any of the mice.

Cholesterol levels increased four times in the mice that ate the high-cholesterol diet and that were predisposed to high cholesterol. Yet cholesterol levels remained normal in the mice which had the cholesterol predisposition but consumed the normal-cholesterol diet.

Some people have mutations in the apoE gene, which controls apoE production. As a result, they cannot adequately maintain blood cholesterol. In humans, this mutation can cause blood cholesterol levels to significantly increase when they eat a diet high in cholesterol, Rikihisa said.

“A high-cholesterol diet really boosted infection levels in the mice without apoE,” Rikihisa said. “The findings suggest that humans may be more susceptible to HGA if they eat a high-cholesterol diet and if they are otherwise prone to high blood cholesterol levels.”

Studies by other researchers have found a link between older age and the level of A. phagocytophilum infection. In one study, infected patients averaged 51 years old, while 39 was the average age for a person infected with Lyme disease.

“Our blood cholesterol levels generally rise as we age,” Rikihisa said. “Someone who suspects he was bitten by a tick needs to seek prompt antibiotic therapy. Additionally, lowering cholesterol levels through diet or with medication may help decrease the chance of developing HGA, or at least reduce the severity of its symptoms.”

A grant from the National Institutes of Health supported this work.

Lowering cholesterol levels (whether through diet and/or medication) may decrease the chance of developing HGA and/or Lyme disease, or at least reduce the severity of symptoms. I'm guessing that a lot more research will need to be carried out to confirm or disprove this hypothesis when it comes to humans.

Edited to add:

Here's a link to the full research article:

J Infect Dis. (2007) 195 (10): 1497-1503.
doi: 10.1086/514819

High-Cholesterol Diet Facilitates Anaplasma phagocytophilum Infection and Up-Regulates Macrophage Inflammatory Protein—2 and CXCR2 Expression in Apolipoprotein E-Deficient Mice

Qingming Xiong, Xueqi Wang and Yasuko Rikihisa

Author Affiliations

Department of Veterinary Biosciences, College of Veterinary Medicine, Ohio State University, Columbus


Conclusion. Our results suggest that high blood cholesterol levels resulting from an interaction between dietary and genetic factors facilitate A. phagocytophilum infection and up-regulate a proinflammatory chemokine and its receptor, which may contribute to HGA pathogenesis.

Posts: 2758
Joined: Thu 1 Jul 2010 8:33

Re: Statins reduce spirochetal burden/modulate immune responses in mouse model of LD

Postby RitaA » Tue 29 Mar 2016 0:06

One (hopefully) last post from me as far as this thread is concerned. For those (like myself) who prefer a more natural (i.e. dietary) approach whenever possible, here's something to consider when it comes to lowering cholesterol levels and reducing inflammation:

Biochem Biophys Res Commun. 2015 Nov 27;467(4):872-8. doi: 10.1016/j.bbrc.2015.10.051. Epub 2015 Oct 19.

Curcumin retunes cholesterol transport homeostasis and inflammation response in M1 macrophage to prevent atherosclerosis.

Chen FY1, Zhou J1, Guo N2, Ma WG1, Huang X1, Wang H1, Yuan ZY1.

Author information

1 Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
2 Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.


Lipoprotein cholesterol metabolism dysfunction in the arterial wall is a major contributor to atherosclerosis, and excessive lipid intake and failed cholesterol homeostasis may accelerate the atherogenic process. Curcumin exerts multiple effects by alleviating inflammation, hyperlipidemia, and atherosclerosis; however, its role in cholesterol transport homeostasis and its underlying impact on inflammatory M1 macrophages are poorly understood. This work aimed to investigate the effect of curcumin on cholesterol transport, the inflammatory response and cell apoptosis in M1 macrophages. RAW264.7 macrophages (M0) were induced with LPS plus IFN-γ for 12 h to develop a M1 subtype and were then incubated with curcumin at different concentrations (6.25 and 12.5 μmol/L) in the presence or absence of oxLDL. Then, cholesterol influx/efflux and foam cell formation as well as inflammation and apoptosis were evaluated. It was found that curcumin increased cholesterol uptake measured by the Dil-oxLDL binding assay, and simultaneously increased cholesterol efflux carried out by Apo-A1 and HDL in M1 cells. Curcumin further reinforced ox-LDL-induced cholesterol esterification and foam cell formation as determined by Oil Red O and BODIPY staining. Moreover, curcumin dramatically reduced ox-LDL-induced cytokine production such as IL-1β, IL-6 as well as TNF-α and M1 cell apoptosis. We also found that curcumin upregulated CD36 and ABCA1 in M1 macrophages. Curcumin increased PPARγ expression, which in turn promoted CD36 and ABCA1 expression. In conclusion, curcumin may increase the ability of M1 macrophages to handle harmful lipids, thus promoting lipid processing, disposal and removal, which may support cholesterol homeostasis and exert an anti-atherosclerotic effect.

Copyright © 2015 Elsevier Inc. All rights reserved.


Cholesterol efflux; Cholesterol uptake; Curcumin; Inflammation; M1 macrophages; PPARγ

PMID: 26471308 [PubMed - indexed for MEDLINE] ... s/curcumin



- Turmeric is a spice derived from the rhizomes of Curcuma longa, a member of the ginger family. Curcuminoids are polyphenolic compounds that give turmeric its yellow color; curcumin is the principal curcuminoid in turmeric.

- The results of phase I clinical trials in colorectal cancer patients suggest that biologically active levels of curcumin can be achieved in the gastrointestinal tract through oral curcumin supplementation. Such trials provide support for further clinical evaluation in people at risk for gastrointestinal cancers. (More information)

- Until the safety and efficacy of curcumin in individuals with cystic fibrosis has been evaluated in clinical trials, the Cystic Fibrosis Foundation does not recommend the use of curcumin as a therapy for cystic fibrosis. (More information)

- Although a few preliminary trials suggest that curcumin may have anti-inflammatory activity in humans, larger randomized controlled trials are needed to determine whether oral curcumin supplementation is effective in the treatment of inflammatory diseases. (More information)

- As a result of promising findings in animal models of Alzheimer’s disease, clinical trials of curcumin supplementation in patients with early Alzheimer’s disease are under way. (More information)


- Turmeric is a spice derived from the rhizomes of Curcuma longa, which is a member of the ginger family (Zingiberaceae). Rhizomes are horizontal underground stems that send out shoots as well as roots. The bright yellow color of turmeric comes mainly from fat-soluble, polyphenolic pigments known as curcuminoids (Figure 1). Curcumin, the principal curcuminoid found in turmeric, is generally considered its most active constituent (1). Other curcuminoids found in turmeric include demethoxycurcumin and bisdemethoxycurcumin. In addition to its use as a spice and pigment, turmeric has been used in India for medicinal purposes for centuries. More recently, evidence that curcumin may have anti-inflammatory and anticancer activities has renewed scientific interest in its potential to prevent and treat disease.

There is lots more to read in the link above. Although it may not be possible to "overdose" on curcumin/turmeric, please be sure to read the "Safety" section.

Return to “Published Studies”

Who is online

Users browsing this forum: No registered users and 1 guest