Low LDL cholesterol associated with worse cognitive performance

Posted on January 20, 2012 by Dr. Jonathan

Summary: cholesterol plays critical roles in cell membranes and steroid hormone production. This study associates low LDL cholesterol with worse cognitive performance. As expected, the effect is amplified by inflammation. Care should be taken to apply a balanced approach to cholesterol lowering therapies.

A truly fascinating study was just published in the journal Neurobiology of Aging investigating lipoproteins and loss of cognitive function. The authors state:

“The aim of this study was to examine the associations between high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides, and cognition and focus on the modifying effect of inflammation.”

They collected biological and cognitive data on 1003 persons ≥ 65 years of age over 6 years of follow-up, measuring cognition with the Mini-Mental State Examination (general cognition), Auditory Verbal Learning Test (memory), and Coding Task (information processing speed). High HDL was associiated with better memory performance, but their data seem to suggest the importance of sufficient LDL cholesterol in brain neuronal membranes:

“We found an independent association between high HDL cholesterol and better memory performance. In addition, low LDL cholesterol was predictive of worse general cognitive performance and faster decline on information processing speed.”

Not at all surprisingly they found that inflammation compounds the adverse effects of low LDL:

“Furthermore, a significant modifying effect of inflammation (C-reactive protein, α-antichymotrypsin) was found. A negative additive effect of low LDL cholesterol and high inflammation was found on general cognition and memory performance.”

And since high triglycerides are commonly provoked by the high insulin levels due to insulin resistance which also have deleterious effects on the brain…

“Also, high triglycerides were associated with lower memory performance in those with high inflammation.”

The authors conclude by suggesting that HDL, LDL and inflammatory indicators can be used as predictors of poor cognitive function:

“Thus, a combination of these factors may be used as markers of prolonged lower cognitive functioning.”

This compels us to use caution and see the ‘big picture’ when designing strategies to manage lipids—care should be taken to not suppress LDL cholesterol to too low a level.

Lifestyle reduction of cardiovascular risk factors improves erectile dysfunction

Posted on September 17, 2011 by Dr. Jonathan

While hormone balance, autonomic nervous system function, anatomic and other factors are necessary aspects of case management for erectile dysfunction, the capacity of the local vascular system to regulate blood delivery to the tissues of interest is as important for sexual as it is for cardiac function. No wonder a paper just published in the Archives of Internal Medicine provides evidence that lifestyle modification of cardiovascular function improves erectile dysfunction. The authors state:

“Erectile dysfunction (ED) shares similar modifiable risks factors with coronary artery disease (CAD). Lifestyle modification that targets CAD risk factors may also lead to improvement in ED. We conducted a systematic review and meta-analysis of randomized controlled trials evaluating the effect of lifestyle interventions and pharmacotherapy for cardiovascular (CV) risk factors on the severity of ED.”

They examined multiple electronic databases from randomized controlled clinical trials with follow-up of at least 6 weeks of lifestyle modification intervention or pharmacotherapy for cardiovascular risk factor reduction. Their main outcome measure was differences in the International Index of Erectile Dysfunction (IIEF-5) score. Their data demonstrated significant effectiveness:

“A total of 740 participants from 6 clinical trials in 4 countries were identified. Lifestyle modifications and pharmacotherapy for CV risk factors were associated with statistically significant improvement in sexual function (IIEF-5 score): weighted mean difference, 2.66. If the trials with statin intervention (n = 143) are excluded, the remaining 4 trials of lifestyle modification interventions (n = 597) demonstrate statistically significant improvement in sexual function: weighted mean difference, 2.40.”

Readers may wish to search this site for several reports on the cautions and limitations associated with statin use. There are, however, no risks associated with skillful lifestyle modification of CV risk factors. The authors conclude:

“The results of our study further strengthen the evidence that lifestyle modification and pharmacotherapy for CV risk factors are effective in improving sexual function in men with ED.”

Heart attacks much more likely after a tiny stroke (TIA)

Posted on March 25, 2011 by Dr. Jonathan

Evidence supporting the expectation that the underlying causal factors resulting in a TIA (transient ischemic attack) also increase the risk of heart attacks was just published in the journal Stroke. The authors first observe that although…

“Coronary artery disease is the leading cause of death after TIA. Reliable estimates of the risk of MI [myocardial infarction = heart attack] after TIA, however, are lacking…Our purpose was to determine the incidence of and risk factors for MI after TIA.”

They cross-referenced data from the Rochester Epidemiology Project for TIA (1985–1994) and MI (1979–2006) to identify all community residents with incident MI after incident TIA. They then compared it to the age-, sex-, and period-specific MI incidences in the general population. What did the data show?

“Relative risk for incident MI in the TIA cohort compared to the general population was 2.09. This was highest in patients younger than 60 years old. “

In other words, having had a TIA doubles the risk of having a heart attack. And very interestingly…

“Increasing age, male sex, and the use of lipid-lowering therapy at the time of TIA were independent risk factors for MI after TIA.”

The hazard ratio for using lipid-lowering therapy (statins) was 3.10, meaning that this tripled the incidence of myocardial infarction.

This study alerts clinicians to think comprehensively and cautiously when considering lipid-lowering agents in cardiovascular prophylaxis after a TIA. Patients who consider a TIA to be a relatively minor event should understand that the underlying causal factors can be a ‘ticking time bomb’ if not addressed. The authors conclude:

“Average annual incidence of MI after TIA is…approximately double that of the general population. The relative risk increase is especially high in patients younger than 60 years old. These data are useful for identifying subgroups of patients with TIA at highest risk for subsequent MI.”

Statins do not decrease mortality in primary prevention

Posted on February 25, 2011 by Dr. Jonathan

A systematic review just published in the journal Evidence-Based Medicine adds more clarity to the proper use of statin medications. Clinicians reading this are likely aware of the controversy raised by the extensive JUPITER trial. The authors note:

“Low-density lipoprotein (LDL) cholesterol (LDL-C) is a risk factor for cardiovascular disease (CVD). Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) lower LDL-C concentrations by about 30–50% and have been shown to reduce mortality in patients with prevalent CVD. However, it is not clear whether statin treatment is beneficial in a primary prevention setting, that is in people without prevalent CVD who are at relatively lower risk. The recent results of the JUPITER trial have fueled an intense debate whether statins should be given for primary prevention of CVD.”

They performed a comprehensive analysis of studies published in the MEDLINE and Cochrane Collaboration databases involving trials of statin use whose subjects were without prevalent CVD at baseline. They performed a detailed meta-analysis employing sophisticated statistical methods with all-cause mortality as the primary outcome of interest. In all, 11 studies involving 65,229 patients met their inclusion criteria, comprising 244,000 person-years of observation. An interesting picture emerged when the numbers were crunched:

“…LDL-C concentration was not predictive of mortality. Statin therapy was not associated with a significant survival benefit…The exclusion of the two trials comprising only patients with diabetes did not substantively change these results. Furthermore, the authors did not find a correlation between mortality reduction and baseline LDL-C concentration or with relative LDL-C reduction in the treatment arm.”

In other words, in this large cohort of patients without already active cardiovascular disease, statin therapy showed no benefit in mortality reduction. The authors state in their conclusion:

“This investigation is by far the largest analysis of statin therapy in a purely primary prevention setting…the authors observed a consistent null result (for statin benefit) independent of mean baseline LDL concentration and mean LDL-C reduction in the treatment arm and without evidence of relevant heterogeneity across cohorts…This study therefore questions the widespread practice of prescribing statins to middle-aged patients with an average cardiovascular risk profile who do not have overt CVD…The inference can be made that individuals with lower cardiovascular risk are likely to benefit even less from statin therapy.”

Statin therapy is not without serious risks and must be pondered carefully for each individual patient. It should not be simply employed as a surrogate for a thorough analysis of the underlying causes promoting dyslipidemia, and most importantly, vascular inflammation—the driving pathological process in cardiovascular disease. The authors further conclude:

“Taken together, the study is the first to meta-analyse statin therapy in a purely primary prevention setting. Its conclusive null result (for statin benefit on all-cause mortality) raises important questions about the current practice of widespread use of statins for primary prevention of CVD in individuals with average cardiovascular risk.”

Should statins be used when someone has had a stroke?

Posted on January 12, 2011 by Dr. Jonathan

A decision analysis just published in the Archives of Neurology offers cautionary evidence that statins should be avoided for people who have suffered an intracerebral hemorrhage (bleeding in the brain). The authors first observe:

“Statins are widely prescribed for primary and secondary prevention of ischemic cardiac and cerebrovascular disease…results from a recent clinical trial suggested increased risk of intracerebral hemorrhage (ICH) associated with statin use. For patients with baseline elevated risk of ICH, it is not known whether this potential adverse effect offsets the cardiovascular and cerebrovascular benefits.”

They used life expectancy measured as as an outcome measure, examining how it varied according to a range of clinical parameters location of hemorrhage, ischemic heart and brain risks, and the magnitude of ICH risk that could be associated with statin use. What did their data show?

“Avoiding statins was favored over a wide range of values for many clinical parameters, particularly in survivors of lobar ICH who are at highest risk of ICH recurrence. In survivors of lobar ICH without prior cardiovascular events, avoiding statins yielded a life expectancy gain of 2.2 quality-adjusted life-years compared with statin use…In patients with lobar ICH who had prior cardiovascular events, the annual recurrence risk of myocardial infarction would have to exceed 90% to favor statin therapy. Avoiding statin therapy was also favored, although by a smaller margin, in both primary and secondary prevention settings for survivors of deep ICH.”

Thus the authors conclude:

“Avoiding statins should be considered for patients with a history of ICH, particularly those cases with a lobar location.“

In an editorial published in the same issue, its author states that despite the many questions that remain:

“The data are, however, generally consistent with the conclusion of the decision analysis—the risk of statin therapy likely outweighs any potential benefit in patients with (at least recent) brain hemorrhage and should generally be avoided in this setting. Until and unless there are data to the contrary, or warranted by specific clinical circumstances, the use of statins in patients with hemorrhagic stroke should be guided by the maxim of nonmaleficence— Primum non nocere.”

Two new studies confirm statins do not help in primary prevention of cardiovascular disease

Posted on June 30, 2010 by Dr. Jonathan

Archives of Internal Medicine Although there is evidence that pharmacological lowering of lipids with statins may reduce mortality when coronary heart disease has already been established, there is a massive accumulation of data that confirm they do not reduce mortality when used for prevention. The authors of a study just published in Archives of Internal Medicine observe:

“…it remains uncertain whether statins have similar mortality benefit in a high-risk primary prevention setting. Notably, all systematic reviews to date included trials that in part incorporated participants with prior cardiovascular disease (CVD) at baseline. Our objective was to reliably determine if statin therapy reduces all-cause mortality among intermediate to high-risk individuals without a history of CVD.”

The authors synthesized data from 11 studies including 65,229 participants encompassing 244,000 person-years. What did the data show?

“The use of statins in this high-risk primary prevention setting was not associated with a statistically significant reduction in the risk of all-cause mortality.”

To fully appreciate the significance of their findings, consider the editorial statement in the same issue:

“Ray and colleagues present what is to date the cleanest and most complete meta-analysis of pharmacological lipid lowering for primary prevention. Limiting the analysis to patients without existing coronary disease is critical because studies that include both groups of patients may appear to show benefit for all patients, when all the benefit accrues to those with existing disease. The patients in their analysis reduced their average levels of low-density lipoprotein cholesterol from 139 to 98 mg/dL and are therefore representative of those being treated in primary care today.”

This puts the authors’ conclusion in perspective:

“This literature-based meta-analysis did not find evidence for the benefit of statin therapy on all-cause mortality in a high-risk primary prevention set-up.”

And this same issue of Archives includes a critical reappraisal of the evidence for the use of statins for prevention from the much-touted JUPITER ((Justification for the Use of Statins in Primary Prevention) study. Their forthright conclusion is consonant with the rest of the evidence:

“The results of the trial do not support the use of statin treatment for primary prevention of cardiovascular diseases and raise troubling questions concerning the role of commercial sponsors.”

IMHO: I consider elevated lipoprotein phospholipase A2 (Lp-PLA2) as evidence of already existing vascular disease even when the person has not suffered a heart attack or stroke. I then seriously consider recommending a natural statin with the appropriate co-factors and customized supports until we confirm that the condition has been brought under control.

Cholesterol crystals are a trigger for local and systemic inflammation. What then?

Posted on June 6, 2010 by Dr. Jonathan

There is an evidence-based middle ground between the dogmas of those who assert that cholesterol is the main cause of cardiovascular disease and those who insist that its contribution is trivial. An interesting paper just published in the Journal of Clinical Lipidology illustrates an important mechanism by which cholesterol crystals trigger an inflammatory response.

“The response to arterial wall injury is an inflammatory process, which over time becomes integral to the development of atherosclerosis and subsequent plaque instability…In this review, a model of plaque rupture is hypothesized with two stages of inflammatory activity.”

In the first stage buildup of cholesterol crystals inside the “foam” cells that accumulate cholesterol induces their death (“apoptosis”); these dead cells elicit an inflammatory response that gathers more lipids into a vulnerable plaque. In stage two further expansion of crystals leads to intimal (blood vessel wall) injury…

“…which can manifest as a clinical syndrome with a systemic inflammation response…We recently demonstrated that when cholesterol crystallizes from a liquid to a solid state, it undergoes volume expansion, which can tear the plaque cap. This observation of cholesterol crystals perforating the cap and intimal surface was made in the plaques of patients who died with acute coronary syndrome.”

The authors refer to their previous work showing that alcohol, aspirin and statins can dissolve cholesterol crystals. Their conclusion:

“…we propose that cholesterol crystallization could help explain in part both local and systemic inflammation associated with atherosclerosis.”

American Journal of Cardiology Of course there are a number of other pathways to inflammation in cardiovascular disease (please see related posts) but this is one of the reasons why I prefer that patients who have both high cholesterol and evidence of inflammation have the benefit of the natural statin derived from red rice yeast with the necessary supportive and protective cofactors including coenzyme Q10. This paper published recently in the American Journal of Cardiology provides evidence that red rice yeast is as effective and better tolerated than the commonly prescribed drug pravastatin:

“The present trial evaluated the tolerability of red yeast rice versus pravastatin in patients unable to tolerate other statins because of myalgia.”

The authors enrolled adults who had to discontinue statins due to muscle pain. Their findings are reassuring for those who prefer a natural alternative to pharma statins:

“The low-density lipoprotein cholesterol level decreased 30% in the red yeast rice group and 27% in the pravastatin group. In conclusion, red yeast rice was tolerated as well as pravastatin and achieved a comparable reduction of low-density lipoprotein cholesterol in a population previously intolerant to statins.”

This is a serious issue. Statin-associated myalgia or the diagnosis rhabdomyolysis does not do justice to the devastating side effects I recently observed in a patient who had a bad reaction to lovastatin.

Atherosclerosis But how do we know when to intervene since high cholesterol alone is not a reliable risk factor and CRP (c-reactive protein) may not be elevated if the inflammation it is supposed to report is also preventing the liver from making it? One very helpful test for discriminating whether high cholesterol is contributing to vascular disease is the lipoprotein-associated phospholipase A2 (Lp-PLA2, PLAC) test, described here in an earlier post, that is associated specifically with inflammation in plaques. Another relies on the fact that it is cholesterol that has been damaged by oxidation that participates in the vascular lesion. To gauge this we can measure lipid peroxides. As this paper published in the journal Atherosclerosis documents, atherosclerosis is strongly associated with the presence of oxidized LDL:

“We investigated the relation between serum lipids including oxidized LDL and the severity of coronary atherosclerosis. Serum lipids and oxidized LDL was measured in 62 men (33–66 years), who underwent diagnostic coronary angiography and sonography to measure the carotid intima-media thickness…Regression analysis indicated that the carotid intima-media thickness and…the ox-LDL:LDL ratio…were the only factors associated independently with the severity of coronary atherosclerosis.”

We have also a fascinating study just published in the German medical journal Seminars in Thrombosis & Hemostasis that shows how oxidized LDL taken up by platelets induces inflammation in the blood vessel:

“Platelets are involved in the initiation of atherosclerosis by adherence to inflamed endothelium…In this study we investigated the functional consequences of oxidized low-density lipoprotein (oxLDL) uptake on platelet function and interaction with the endothelium.”

The authors were actually able to visualize the intracellular vesicles (microscopic sacs) containing the oxidized LDL using immunoflorescence microscopy. They made a fascinating observation: the platelets containing oxLDL provoked more cellular stickiness than regular LDL, oxLDL in the bloodstream or platelets without oxLDL.

“Furthermore, oxLDL-laden platelets induced foam cell development from CD34+ progenitor cells. On endothelial regeneration, oxLDL-laden platelets had the opposite effect: The number of CD34+ progenitor cells (colony-forming units) able to transform into endothelial cells was significantly reduced in the presence of oxLDL-platelets, whereas native LDL had no effect.”

This is a striking insight: it was only the oxidized LDL that prevented the endothelial cells (lining the blood vessel wall) from repairing, not the ‘native’ LDL.

Doctors and patients alike need to bear in mind the summary of their findings:

“Our results demonstrate that activated platelets internalize oxLDL and that oxLDL-laden platelets activate endothelium, inhibit endothelial regeneration, and promote foam cell development. Platelet oxLDL contributes significantly to vascular inflammation and is able to promote atherosclerosis.”

Lipids But, you may ask, since diabetes and pre-diabetes (metabolic syndrome) are so strongly associated with cardiovascular disease shouldn’t there be some kind of connection here? This study published in the journal Lipids shows the evidence that there is.

“Oxidized low-density lipoprotein (ox-LDL) plays a key role in the progression of atherosclerosis and diabetes complications. The aim of this study was first, to evaluate the association between ox-LDL and diabetes duration, and second, to examine serum level of ox-LDL in patients with prolonged diabetes and a desirable LDL-cholesterol level.”

It’s important to appreciate that the study group had ‘regular’ LDL in the desirable range, so a typical blood test would appear to be fine. Their very interesting observation is that the longer the person had diabetes (= the longer the risk factor for cardiovascular disease was building up) the more oxLDL they had in proportion to regular LDL:

“The ox-LDL-to-LDL ratio was dramatically higher in patients with diabetes duration >5 years in comparison to newly diagnosed patients and healthy participants. Ox-LDL was significantly associated with diabetes duration.”

Their final comments must be borne in mind by anyone caring for patients with both diabetes and a significant burden of insulin resistance:

“In conclusion, this study showed that the serum ox-LDL level increases with the length of diabetes, even though the patients’ LDL-cholesterol level is maintained at a desirable level. Our findings highlight that possibly more attention should be focused on markers of oxidative stress in the management of lipids in diabetic patients.”

Can we reliably measure oxidized LDL as implied by the lab test mentioned above? This study published in the journal Blood Pressure assure us that we can:

“Cardiovascular diseases are accompanied by the presence of active oxygen species and organic free radical generation. The aim of this study was to examine the possibility of using malondialdehyde (MDA)-modified low-density lipoprotein (LDL) analyses as a diagnostic and prognostic biomarker.”

MDA-modified LDL is the same as oxLDL. What conclusion did they draw from their data?

“MDA-modified LDL estimation has a diagnostic accuracy and may be used as an independent biochemical marker for atherosclerosis.”

Truthfully, the functional approach to cardiovascular disease encompasses a number of other important aspects, but I’m wondering if you’ve gotten this far. As a reward for your diligence I’ll conclude this limited post with a few interesting items of satisfying practical significance. First we have a paper just published in The Journal of Steroid Biochemistry & Molecular Biology that reassures us of the benefit of vitamin D in the prevention and treatment of cardiovascular disease.

“Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). In type 2 diabetics, the prevalence of vitamin D deficiency is 20% higher than in non-diabetics, and low vitamin D levels nearly double the relative risk of developing CVD compared to diabetic patients with normal vitamin D levels.”

The authors endeavored to uncover the mechanism behind vitamin D’s benefit:

“We found that 1,25-dihydroxy vitamin D3 [1,25(OH)2D3] suppressed foam cell formation by reducing acetylated low density lipoprotein (AcLDL) and oxidized low density lipoprotein (oxLDL) cholesterol uptake in diabetics only. …In addition, 1,25(OH)2D3…improved insulin signaling, downregulated SR-A1 expression, and prevented oxLDL- and AcLDL-derived cholesterol uptake.”

You can remember their conclusion when getting your vitamin D level checked:

“The results of this research reveal novel insights into the mechanisms linking vitamin D signaling to foam cell formation in diabetics and suggest a potential new therapeutic target to reduce cardiovascular risk in this population.”

Throw some nuts in there too. A nice original study was published not long ago in The Anatolian Journal of Cardiology evaluated the benefit of hazelnuts (filberts) on atherosclerosis. The authors observed a number of interesting effects:

“Lag time for oxidation and α-tocopherol content of LDL were found to be increased while ox-LDL levels decreased during the study period. Total cholesterol, LDL-cholesterol, apolipoprotein (apo) B and apo B/apo AI ratio were found to be significantly lower while apo AI was higher. In respect to LDL subfraction, ratio of large/small LDL was significantly increased at the end of the study.”

They summed up their ‘take home’ message on hazelnuts (which earlier posts suggest applies to most if not all nuts) accordingly:

“Hazelnut-enriched diet may play important role in decrease in atherogenic tendency of LDL by lowering the susceptibility of LDL to oxidation and plasma ox-LDL levels, and increasing the ratio of large/small LDL beyond its beneficial effect on lipid and lipoprotein levels.”

Digestive Diseases and Sciences Helicobacter pylori infection is, as you likely know, extremely common—according to WHO the most common infection in the world. It is a causative agent in almost all gastric ulcers. We see it here all the time. Finding out if you have it and getting it treated is another important therapeutic point for cardiovascular disease as this paper just published in the journal Digestive Diseases and Sciences reminds us. The authors investigated the impact of H. pylori infection on coronary atherosclerosis by examining the effects of infection on levels of serum lipid, high-sensitivity C-reactive protein (hsCRP) and oxidized low-density protein (oxLDL). What did their data show?

“The levels of total cholesterol, LDL, apolipoprotein B, serum hsCRP, oxLDL were significantly elevated and the severity of coronary atherosclerosis was significantly increased in H. pylori…group.”

Their conclusion echoes the findings of other investigators:

“More serious coronary atherosclerosis was observed in CHD patients with H. pylori…infection. H. pylori…infection might be involved in coronary atherosclerosis by modifying serum lipids, enhancing LDL oxidation, and activating the inflammatory responses.”

Remember, the most reliable ways to diagnose H. pylori infection are by stool antigens, a provoked breath test, or PCR (DNA amplification). H. pylori antibodies are not dependable.

Although it’s a major topic that deserves more space, mention at least much be made of the autoimmune aspect of cardiovascular disease as described in this recent paper published in the journal Angiology:

“Atherosclerosis is now recognized as a chronic inflammatory disease and is characterized by features of inflammation at all stages of its development. It also appears to display elements of autoimmunity, and several autoantibodies including those directed against oxidized low-density lipoprotein (ox-LDL) and heat shock proteins (Hsps) have been identified in atherosclerosis.”

The authors then describe their investigation of immune complexes, antibodies and receptor signaling in this process. Certain cases demand a thorough evaluation of the autoimmune component of their CVD.

It would also not be appropriate to close without at least alluding to the influence of hormones on cardiovascular disease, a topic that has many aspects treated in other posts. This paper recently published in the journal Endocrinology makes a very important but little known point for men (for whom most everyone knows that too little testosterone or excess conversion to estrogen is a big risk factor for CVD). Testosterone is normally converted into its dihydrotestosterone form (DHT) which does a lot of the heavy lifting because it’s ten times stronger than the original. Men with prostate disease are commonly prescribed medications (including saw palmetto) that block the conversion of testosterone to DHT, but without first measuring the levels of the bioactive forms of these hormones. These medications don’t always help because not everyone with a prostate condition has too much DHT. Moreover, DHT is important for protection against cardiovascular disease. The authors…

“…investigated the effect of…dihydrotestosterone (DHT) on the rabbit atherogenesis in relation to…oxidized-low-density lipoprotein receptor-1 (LOX-1) and its downstream molecules.”

What did they find?

“…DHT significantly reduced HCD-induced [high cholesterol diet-induced] foam cell formation…DHT inhibited the formation of foam cells induced by oxidized low-density lipoprotein. Moreover, the expression of LOX-1 and inflammatory cytokines in the cultured macrophages was significantly suppressed by DHT.”

Inappropriately blocking the conversion of testosterone to DHT can thus open a door to cardiovascular disease. So remember, both gentlemen and ladies: no hormone interventions without measuring the free-fraction bioactive levels before and after!

Major depression and low Coenzyme Q10

Posted on January 18, 2010 by Dr. Jonathan

Neuroendocrinology Letters Brain inflammation and oxidative stress are important aspects of the biological component of major depression. The authors of this interesting paper recently published in the journal Neuro Endocrinology Letters state that “There is now evidence that major depression is accompanied by an induction of inflammatory and oxidative and nitrosative stress (IO&NS) pathways and by a lowered antioxidant status. Coenzyme Q10 (CoQ10) is a strong antioxidant that has anti-inflammatory effects.” They go on to report “We found that plasma CoQ10 was significantly (p=0.0002) lower in depressed patients than in normal controls,” and note a particularly strong correlation in those with treatment resistant depression (TRD) or chronic fatigue (CFS). They find “The results show that lower CoQ10 plays a role in the pathophysiology of depression and in particular in TRD and CFS accompanying depression.” Interestingly, they conclude with an observation that links the cholesterol lowering statin drugs to the risk of depression: “Since statins significantly lower plasma CoQ10, depressed patients and in particular those with TRD and CFS represent populations at risk to statin treatment.”