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.

Brazil nuts improve lipids, oxidative stress and blood vessel function in obese adolescents

Posted on November 24, 2011 by Dr. Jonathan

Summary: Brazil nuts protect against vascular disease in overweight female adolescents.

Recent research published in the journal Nutrition & Metabolism offers evidence that Brazil nuts, besides being more effective at raising serum selenium levels than selenium taken as a supplement, improve the lipid profile and protect against blood vessel damage. The authors state:

“Obesity is a chronic disease associated to an inflammatory process resulting in oxidative stress that leads to morpho-functional microvascular damage that could be improved by some dietary interventions. In this study, the intake of Brazil nuts (Bertholletia excelsa), composed of bioactive substances like selenium, α- e γ- tocopherol, folate and polyunsaturated fatty acids, have been investigated on antioxidant capacity, lipid and metabolic profiles and nutritive skin microcirculation in obese adolescents.”

Their study subjects comprising obese female adolescents were randomized to a group that consumed 15-25 g/day of Brazil nuts in capsules for 16 weeks and a placebo group. Anthropometry, metabolic-lipid profiles, oxidative stress, capillary diameters, functional capillary density, red blood cell velocity (RBCV) were measured at baseline (T0) and after the Brazil nut intervention (T1). What did the data show?

“At T1, BNG [the Brazil nut group] had increased selenium levels, RBCV and RBCVmax and reduced total (TC) and LDL-cholesterol. Compared to PG [placebo group], Brazil nuts intake reduced TC, triglycerides and LDL-ox and increased RBCV.”

In other words, compared to the placebo group, the Brazil nut cohort had better blood vessel function, lower total and LDL cholesterol and, importantly, reduced oxidized cholesterol (LDL-ox, the truly ‘bad’ cholesterol). Naturally, they also had higher selenium levels. The authors conclude:

“Brazil nuts intake improved the lipid profile and microvascular function in obese adolescents, possibly due to its high level of unsaturated fatty acids and bioactive substances.

Fasting before blood tests may not be necessary for children

Posted on August 17, 2011 by Dr. Jonathan

With the unprecedented expansion of overweight, obesity and pre-diabetes in the pediatric population it is becoming increasing important to evaluate metabolic status with appropriate blood tests at a younger age. Anything that makes this task less onerous is desirable. A welcome study just published in the journal Pediatrics offers evidence that fasting may not be necessary to reliably evaluate lipid status in children. The authors state:

“Fasting lipid panels are recommended to screen for lipid abnormalities; however, fasting can be difficult for children and make screening difficult. Results of studies in adult patients are raising questions of whether fasting is needed before lipid screening.”

They examined total cholesterol (TC), HDL (high-density lipoprotein), LDL (low-density lipoprotein), and triglyceride cholesterol components in relation to fasting in 12,744 children aged 3 to 17 (varying times for young children and the usual fasting for those older than 12 years). The data appear to give kids a break:

“TC, HDL, LDL, or triglyceride values were available for 12 744 children. Forty-eight percent of the TC and HDL samples and 80% of the LDL and triglyceride samples were collected from children who had fasted ≥8 hours. Fasting had a small positive effect for TC, HDL, and LDL, resulting in a mean value for the sample that was 2 to 5 mg/dL higher with a 12-hour fast compared with a no-fast sample. Fasting time had a negative effect on triglycerides, which resulted in values in the fasting group that were 7 mg/dL lower.”

Furthermore…

“For TC, nonfasting screening inappropriately classifies ≈1% of children as normal, who would have had borderline values with fasting. In addition, ≈1% of children with borderline nonfasting values would actually have elevated results if fasting. For LDL, 1.2% of children with borderline fasting levels would have normal results postprandially, and 1.6% of children with increased calculated LDL while fasting, would now be considered to have borderline results. For triglycerides,≈4% of the children classified with normal triglycerides when fasting would have elevated values postprandially.”

In other words, most of the time the difference between fasting and non-fasting in children is not clinically significant.

The authors conclude:

“Comparing a nationally representative cross-section of children who had fasted for various lengths of time, we demonstrated that nonfasting measurements of TC, calculated LDL, and HDL cholesterol values had only small differences from fasting values. Although statistically significant, these differences are unlikely to result in important clinical changes in the results of screening for cholesterol abnormalities. …Across a large, nationally representative sample of children, the levels of TC, HDL, non-HDL cholesterol, and LDL cholesterol vary minimally on the basis of fasting time. It is not known if these small differences in lipoprotein components consistently weaken or strengthen the usefulness of lipid values for the assessment of current health risks or prediction of future cardiovascular risks, but it is clear that testing regardless of fasting status would reduce barriers to screening. Therefore, future research with people in longitudinal samples is warranted. If those results confirm our findings, professional societies might wish to reconsider their recommendations and encourage providers follow lipid screening guidelines at the point of care, regardless of fasting status.”

It will be helpful if future studies can offer data specifically quantifying the impact of fasting versus non-fasting on subsequent cardiovascular and metabolic risks. However, on the basis of the evidence we have now, my personal preference is to make it as easy on the kids as possible. Fasting a galloping pediatric metabolism risks a low blood sugar state that is not only globally miserable but elicits a vasoconstrictive autonomic response that makes phlebotomy much more difficult and traumatic.

Sugar turns LDL cholesterol “ultra-bad”

Posted on June 19, 2011 by Dr. Jonathan

That serving of french toast may be doing more to contribute to cardiovascular disease than promoting insulin resistance and dyslipidemia. A paper just published in the journal Diabetes details how excess blood sugar causes LDL cholesterol to stick more readily to arterial plaque. Inflamed vulnerable plaque on arterial walls is the main precipitating factor for heart attacks and strokes. The authors set out to…

“…study whether modification of LDL by methylglyoxal (MG), a potent arginine-directed glycating agent that is increased in diabetes, is associated with increased atherogenicity.”

Glycation is the damaging process by which sugar binds to substances in the body that it shouldn’t do normally. As the practitioners reading this know, hemoglobin A1c (HbgA1c, produced by glycation of hemoglobin) is an important laboratory metric for determining how high a person’s blood sugar has been on average over the previous few months. People with pre-diabetes (metabolic syndrome) and type 2 diabetes have higher levels. By modifying human LDL by methylglyoxal to reproduce what happens in vivo, the authors were able to measure the effect on LDL particle characteristics and its tendency to deposit in the arterial wall. What did they find?

“MGmin-LDL [glycated LDL] had decreased particle size, increased binding to proteoglycans, and increased aggregation in vitro. Cell culture studies showed that MGmin-LDL was bound by the LDL receptor but not by the scavenger receptor and had increased binding affinity for cell surface heparan sulfate–containing proteoglycan. Radiotracer studies in rats showed that MGmin-LDL had a similar fractional clearance rate in plasma to unmodified LDL but increased partitioning onto the aortal wall…A computed structural model predicted that MG modification of apoB100 induces distortion, increasing exposure of the N-terminal proteoglycan–binding domain on the surface of LDL. This likely mediates particle remodeling and increases proteoglycan binding.”

In other words, glycated LDL is a nasty compound that is less likely to be scavenged from the bloodstream; and it is smaller, denser and stickier than normal LDL so that it has a higher tendency to adhere to the blood vessel well. Glycated LDL has been called the “ultra-bad cholesterol“. It also shows part of the reason why blood sugar lowering therapies reduce cardiovascular disease. The authors conclude:

“MG modification of LDL forms small, dense LDL with increased atherogenicity that provides a new route to atherogenic LDL and may explain the escalation of cardiovascular risk in diabetes and the cardioprotective effect of metformin.”

Low cholesterol associated with higher mortality

Posted on January 21, 2011 by Dr. Jonathan

Most readers here are aware that cholesterol is the substrate for all steroid hormones and a component of all cell membranes, so that when too low it is a contributing factor to a range of disorders. A study just published in the Journal of Epidemiology provides more evidence for the association between low cholesterol and death from all causes. The authors state:

“We investigated the relationship between low cholesterol and mortality and examined whether that relationship differs with respect to cause of death.”

They conducted their study using 12,334 healthy adults from 12 rural areas in Japan. They correlated serum total cholesterol with total mortality, noting sex and cause of death. The average follow-up period was 11.9 years. What did their data show?

“As compared with a moderate cholesterol level (4.14-5.17 mmol/L)[161.5-201.5 mg/dL], the age-adjusted hazard ratio (HR) [risk] of low cholesterol (<4.14 mmol/L)[161.5 mg/dL] for mortality was 1.49 [50% increase in mortality]… High cholesterol (≥6.21 mmol/L)[≥242 mg/dL] was not a risk factor. This association was unchanged in analyses that excluded deaths due to liver disease… The multivariate-adjusted HRs [hazard ratios = risks]…of the lowest cholesterol group for hemorrhagic stroke, heart failure (excluding myocardial infarction), and cancer mortality [were] significantly higher than those of the moderate cholesterol group, for each cause of death.”

Numerous lines of reasoning, documented in a broad accumulation of scientific evidence (of which a small ‘taste’ is reported in this venue) converge on the assertion that inflammation, rather than cholesterol per se, is the primary villain in cardiovascular disease. Clinicians and patients alike should bear in mind the authors’ conclusion:

“Low cholesterol was related to high mortality even after excluding deaths due to liver disease from the analysis. High cholesterol was not a risk factor for mortality.“

Why measuring oxidized LDL (lipid peroxides) is important

Posted on November 23, 2010 by Dr. Jonathan

Cholesterol is the precursor for all steroid hormones and a constituent of every cell membrane, but it participates in cardiovascular diseases (in which blood vessels are damaged by inflammation) when it becomes damaged by oxidation. A paper just published in the Journal of Vascular Research elucidates the molecular mechanisms by which oxidized LDL damages blood vessels. Specifically, the authors…

“…tested the hypothesis that oxidized low-density lipoprotein (oxLDL)-induced inactivation of Akt within endothelial progenitor cells (EPCs) is mediated at the level of Phosphoinositide 3-kinase (PI3K), specifically by nitrosylation of the p85 subunit of PI3K, and that this action is critical in provoking oxLDL-induced EPC apoptosis.”

Endothelial progenitor cells play a critical role in repair of blood vessel walls. When their function is impaired there is a much greater risk of cardiovascular disease. EPC apoptosis is the death of these important cells. Akt is a kinase ‘signaling molecule’ that prevents apoptosis. Additionally, the PI3K pathway is necessary for normal blood vessel function through endothelial nitric oxide synthase (eNOS) which produces the beneficial nitric oxide that instigates blood vessel relaxation, endothelial growth and repair. When oxidized LDL (oxLDL) is taken up by EPCs they are subject to oxidative stress that impairs their survival. Specifically what did they find when EPCs were exposed to oxLDL?

“oxLDL increased O2– and H2O2 in these cells and induced a dose- and time-dependent reduction in the p-Akt/Akt ratio and increase in EPC apoptosis. These effects were significantly reduced by the antioxidants superoxide dismutase, L-NAME, epicatechin and FeTPPs. oxLDL also induced nitrosylation of the p85 subunit of PI3K…an effect significantly reduced by all the antioxidant agents tested.”

In other words, the ‘bad news’ is that oxidized LDL is ‘death’ to blood vessel cells; the ‘good news’ is that the antioxidants that were examined can protect against this effect. Thus the authors conclude:

“The present findings indicate that oxLDL disrupts the PI3K/Akt signaling pathway at the level of p85 in EPCs. This dysfunction can be reversed by ex vivo antioxidant therapy.”

The serum lipid peroxides (blood) test is our objective indicator for the amount of LDL oxidation.

Cholesterol levels vary with the menstrual cycle

Posted on August 13, 2010 by Dr. Jonathan

A study recently published in The Journal of Clinical Endocrinology & Metabolism proves that we must take the menstrual cycle into consideration when testing cholesterol in cycling women.

“The objective of the study was to evaluate the association between endogenous [internally produced] estrogen and serum lipoproteins across the menstrual cycle.”

The authors found that total and LDL cholesterol were lower during the luteal phase (second half, when progesterone is higher) than the follicular phase:

“More women were classified above the desirable range (LDL ≥130 mg/dl or total cholesterol ≥200 mg/dl) when measured during the follicular phase [first half].”

HDL was higher when estradiol had peaked, corresponding also to lower LDL and triglycerides.

“Because lipoprotein cholesterol levels vary across the menstrual cycle, cyclic variations in lipoprotein levels may need to be considered in the design and interpretation of studies in reproductive-age women and in the clinical management of women’s cholesterol.“

Your brain controls your cholesterol level

Posted on June 20, 2010 by Dr. Jonathan

Yet another reason to ascertain the functional integrity of the brain and central nervous system for chronic degenerative disease and aging is presented in this interesting paper in the journal Nature Neuroscience. An editorial commenting on this study just published in Science Translational Medicine comments:

“Early on, it was thought that the cholesterol we eat is a major determinant of our circulating cholesterol levels, and many people tried to avoid eating cholesterol-rich foods like egg yolks, meat, and dairy products in order to lower their blood cholesterol. It turned out, however, that the amount of cholesterol we eat has only a modest impact on our blood cholesterol concentrations…Because the brain controls metabolic functions such as hepatic glucose production and lipid metabolism in fat, it is reasonable to think that the brain might also regulate the metabolic pathways that control circulating cholesterol. Now Perez-Tilve et al. have demonstrated in a series of studies that this is the case.”

The authors who performed the research state:

“We found that the CNS is also an important regulator of cholesterol in rodents. Inhibiting the brain’s melanocortin system by pharmacological, genetic or endocrine mechanisms increased circulating HDL cholesterol by reducing its uptake by the liver independent of food intake or body weight.”

In the course of their experiments they made this interesting observation”

“We found that the gut-brain control of cholesterol metabolism is independent of changes in food intake or body weight.”

Noting that the gut hormone ghrelin increased fat storage and cholesterol, they then determined that melanocortin in the brain controls ghrelin expression. They demonstrated that inhibiting melanocortin increased cholesterol by inhibiting its clearance from the bloodstream. They then showed that activating the brain melanocortin system decreased cholesterol levels. They conclude with this promising statement:

“…circulating levels of cholesterol are under remote, but direct, control of specific neuroendocrine circuits in the CNS…Direct or indirect pharmacological modulation of hypothalamic melanocortin tone may offer a potent way to treat hypercholesterolemia and to simultaneously target all major components of the metabolic syndrome.

Science Translational Medicine And the editorial further states:

“These findings also suggest that other brain signals—nutrients, emotions, and stress, for example—could also regulate cholesterol metabolism. This may be a mechanism through which alternative medicine practices such as acupuncture and aromatherapy could regulate cardiovascular risk factors. These techniques can modulate the autonomic nervous system, which is probably the main peripheral mediator of the brain control of cholesterol metabolism.”

This is another reason why regulating the central and autonomic nervous systems is a fundamental element in our approach to treatment, and why profiling the autonomic nervous system with heart rate variability analysis is so valuable.

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!

More reasons to go nuts for heart disease

Posted on May 18, 2010 by Dr. Jonathan

A paper just published in the Archives of Internal Medicine analyzes the evidence from 25 intervention trials on the effect of eating nuts on blood lipid levels and heart disease. The authors begin by noting:

“Epidemiological studies have consistently associated nut consumption with reduced risk for coronary heart disease…The objectives of this study were to estimate the effects of nut consumption on blood lipid levels and to examine whether different factors modify the effects.”

They pooled the data from 25 trials in 7 countries for cholesterol, LDL, ratio of LDL to HDL, and triglycerides. Improvements were documented in all of these factors. The data also showed that:

“The effects of nut consumption were dose related, and different types of nuts had similar effects on blood lipid levels…the lipid-lowering effects of nut consumption were greatest among subjects with high baseline LDL-C and with low body mass index and among those consuming Western diets.”

In other words, eating more nuts improved the lipid-lowering effect. Hence their conclusion:

“Nut consumption improves blood lipid levels in a dose-related manner, particularly among subjects with higher LDL-C or with lower BMI.”