Statin drugs don't help prevent heart attacks--American Medical Journal
LDL immune sytem role, and on Liver textbook
LDL through immune function lenghten life--journal articles
Recommended Journal Articles
LDL through immune function lenghten life--journal articles

To lower LDL with drugs is bad medicine, as the articles demonstrate.  Not only does it make the patient more vulnerable to infection through lowering the immune function of LDL, but it also increases mortality in the elderly (those who take statins)—see bottom study.  Low level of LDL in population study is associated with higher rate of mortality.  This finding has been confirmed both in the Framingham Study but also in a Chinese study—bottom. Among the Chinese oldest old, higher LDL-C level was associated with lower risk of all-cause mortality.”    Cholesterol (especially LDL) is a marker for inflammation within artery walls caused by pathogens.  This infectious process is the single most significant cause for cardiovascular disease. Reducing an immune function that counters the effect of gram negative bacteria (half of all bacteria are gram negative) in the arteries promotes cardiovascular disease.  LDL found in artery walls are like firemen found at a fire—a symptom of a problem.  Both are called to the scene of the problem.  LDL is actively transported through receptors for LDL on the endothelial cells that line the arteries.  But pharma following the dollar (tobacco ethics) and teaches doctors to lower LDL with statin drugs.    

More journal articles on LDL’s immune functions http://healthfully.org/rl/id8.html, http://healthfully.org/rja/id1.html, and http://healthfully.org/rja/id1.html and review article on infections causing pathogenesis of atherosclerosis  by Uffre Ravnskov and Kilmer McCully

http://jem.rupress.org/content/182/1/267.abstract   http://jem.rupress.org/content/182/1/267.full.pdf+html

July 1, 1995 // JEM vol. 182 no. 1 267-272 

Triglyceride-rich lipoproteins prevent septic death in rats.

  1. T E ReadC GrunfeldZ L KumwendaM C CalhounJ P KaneK R Feingold, and J H Rapp


    Triglyceride-rich lipoproteins bind and inactive bacterial endotoxin in vitro and prevent death when given before a lethal dose of endotoxin in animals. However, lipoproteins have not yet been demonstrated to improve survival in polymicrobial gram-negative sepsis. We therefore tested the ability of triglyceride-rich lipoproteins to prevent death after cecal ligation and puncture (CLP) in rats. Animals were given bolus infusions of either chylomicrons (1 g triglyceride/kg per 4 h) or an equal volume of saline for 28 h after CLP. Chylomicron infusions significantly improved survival (measured at 96 h) compared with saline controls (80 vs 27%, P < or = 0.03). Chylomicron infusions also reduced serum levels of endotoxin, measured 90 min (26 +/- 3 vs 136 +/- 51 pg/ml, mean +/- SEM, P < or = 0.03) and 6 h (121 +/- 54 vs 1,026 +/- 459 pg/ml, P < or = 0.05) after CLP. The reduction in serum endotoxin correlated with a reduction in serum tumor necrosis factor, measured 6 h after CLP (0 +/- 0 vs 58 +/- 24 pg/ml, P < or = 0.03), suggesting that chylomicrons improve survival in this model by limiting macrophage exposure to endotoxin and thereby reducing secretion of inflammatory cytokines. Infusions of a synthetic triglyceride-rich lipid emulsion (Intralipid; KabiVitrum, Inc., Alameda, CA) (1 g triglyceride/kg) also significantly improved survival compared with saline controls (71 vs 27%, P < or = 0.03). These data demonstrate that triglyceride-rich lipoproteins can protect animals from lethal polymicrobial gram-negative sepsis.




    Inhibition of endotoxin-induced activation of human monocytes by human lipoproteins.

  1. W A FlegelA WölplD N Männel and  H Northof


Toxicity of lipopolysaccharide (LPS) (endotoxin) is, to a large extent, mediated by the activation of monocytes/macrophages and subsequent release of monokines, such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha). It is known that LPS binds readily to serum lipoproteins and that LPS-lipoprotein complexes are less toxic than unbound LPS. Here we present data analyzing the impact of the LPS-serum interaction at the cellular level. By measuring IL-1 TNF-alpha, and IL-6, the interaction of different LPSs or lipid A with human serum could be shown to prevent the activation of human monocytes. The amounts of LPS inactivated by normal human serum did not exceed 10 ng/ml. The LPS-inactivating capacity of serum was shown to be a function of the lipoproteins. Other serum components, such as naturally occurring anti-LPS immunoglobulin G, complement, or nutritive lipids, had no significant influence in our system. Our experiments suggest that serum lipoproteins control endotoxin-induced monocyte activation and monokine release.




Triglyceride-Rich Lipoproteins as Agents of Innate Immunity




Bacterial endotoxin (i.e., lipopolysaccharide [LPS]) elicits dramatic responses in the host, including elevated plasma lipid levels due to increased synthesis and secretion of triglyceride-rich lipoproteins by the liver and inhibition of lipoprotein lipase. This cytokine-induced hyperlipoproteinemia, clinically termed the “lipemia of sepsis,” was customarily thought to involve the mobilization of lipid stores to fuel the host response to infection. However, because lipoproteins can also bind and neutralize LPS, we have long postulated that triglyceride-rich lipoproteins (very-low-density lipoproteins and chylomicrons) are also components of an innate, nonadaptive host immune response to infection. Recent research demonstrates the capacity of lipoproteins to bind LPS, protect against LPS-induced toxicity, and modulate the overall host response to this bacterial toxin.

Thematic review series: The Pathogenesis of Atherosclerosis. 

Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host



Infection and inflammation induce the acute-phase response (APR), leading to multiple alterations in lipid and lipoprotein metabolism. Plasma triglyceride levels increase from increased VLDL secretion as a result of adipose tissue lipolysis, increased de novo hepatic fatty acid synthesis, and suppression of fatty acid oxidation. With more severe infection, VLDL clearance decreases secondary to decreased lipoprotein lipase and apolipoprotein E in VLDL. In rodents, hypercholesterolemia occurs attributable to increased hepatic cholesterol synthesis and decreased LDL clearance, conversion of cholesterol to bile acids, and secretion of cholesterol into the bile. Marked alterations in proteins important in HDL metabolism lead to decreased reverse cholesterol transport and increased cholesterol delivery to immune cells. Oxidation of LDL and VLDL increases, whereas HDL becomes a proinflammatory molecule. Lipoproteins become enriched in ceramide, glucosylceramide, and sphingomyelin, enhancing uptake by macrophages. Thus, many of the changes in lipoproteins are proatherogenic. The molecular mechanisms underlying the decrease in many of the proteins during the APR involve coordinated decreases in several nuclear hormone receptors, including peroxisome proliferator-activated receptor, liver X receptor, farnesoid X receptor, and retinoid X receptor.

APR-induced alterations initially protect the host from the harmful effects of bacteria, viruses, and parasites. However, if prolonged, these changes in the structure and function of lipoproteins will contribute to atherogenesis  [Just like firemen contribute to water damage in a building]. 


LPS is lipopolysaccharide binding protein The protein encoded by this gene is involved in the acute-phase immunologic response to gram-negative bacterial infections. Gram-negative bacteria contain a glycolipid, lipopolysaccharide (LPS), on their outer cell wall. Together with bactericidal permeability-increasing protein (BPI), the encoded protein binds LPS and interacts with the CD14 receptor, probably playing a role in regulating LPS-dependent monocyte responses. Studies in mice suggest that the encoded protein is necessary for the rapid acute-phase response to LPS but not for the clearance of LPS from circulation..  Wiki.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC199173/   FULL Posted at http://healthfully.org/rja/id1.html

LPS-binding protein circulates in association with apoB-containing lipoproteins and enhances endotoxin-LDL/VLDL interaction


LPS-binding protein (LBP) and serum lipoproteins cooperate in reducing the toxic properties of LPS. In the present study, we demonstrate that LBP circulates in association with LDL and VLDL in healthy persons. ApoB was found to account at least in part for the interaction of LBP with LDL and VLDL. Although LBP interacted with purified apoA-I in vitro, no association of LBP with apoA-I or HDL was found in serum. Consistent with the observed association of LBP with LDL and VLDL, these lipoproteins also were demonstrated to be the predominant LPS-binding lipoproteins. Most interestingly, the association of LBP with LDL and VLDL strongly enhanced the capacity of these lipoproteins to bind LPS. Because this function of LBP is of utmost importance during infection, the association of LBP and LPS with lipoproteins was also studied in serum from septic patients. In septic serum containing high LBP levels and a markedly altered lipoprotein spectrum, most of the LBP is associated with LDL and VLDL, although some LBP appeared to circulate free from lipoproteins. Also in this serum, LPS was found to bind predominantly to LDL and VLDL. The observed binding of LBP and LPS to LDL and VLDL, as well as the LBP-dependent incorporation of LPS into these lipoproteins, emphasizes a crucial role for circulating LBP-LDL/VLDL complexes in the scavenging of LPS.

Body of articles selected by JK

“This initiation of cellular responses is essential for the host defense against bacterial infections,,,, LPS is detoxified in the circulation by incorporation into lipoproteins (reviewed in ref. … Evidence for a physiological role for LBP in inflammation is supported by studies that demonstrate enhanced mortality and uncontrolled multiplication and spread of bacteria in LBP knockout mice compared with wild-type mice after intraperitoneal administration of bacteria ()…. We consider that the physical association of LBP with these lipoproteins may be important for the cooperation of LBP and lipoproteins in the detoxification of endotoxin….   Because it is firmly established that LDL and VLDL are critical in the survival of infection with gram-negative bacteria () and that circulating levels of these lipoproteins are relatively high during inflammation compared with HDL levels, the present study was undertaken to investigate whether LBP associates with LDL and VLDL. To this end, the distribution of LBP among lipoproteins was studied in serum of healthy and septic persons. Subsequently, we investigated the effect of the association of LBP with lipoproteins and apolipoproteins on the LPS-binding capacity…. The beneficial role for LDL in the host defense against bacteria is supported by a study that demonstrates that LDL-receptor–deficient mice with elevated circulating LDL concentrations are protected against lethal endotoxemia and severe infections with gram-negative micro-organisms (). … Overall, the data of this study suggest that LBP is a cofactor of circulating LDL and VLDL, which facilitates the uptake of endotoxin by these lipoproteins. This implies an important role for LBP/LDL and VLDL complexes in the defense against bacteria and endotoxin.”


11. Jack RS, et al. Lipopolysaccharide-binding protein is required to combat a murine gram-negative bacterial infection. Nature. 1997;389:742–745. [PubMed]


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441211/  FULL         Published in final edited form as:

Atherosclerosis. 2015 Mar; 239(1): 137–142.


Low-density Lipoprotein Cholesterol was Inversely Associated with 3-Year All-Cause Mortality among Chinese Oldest Old: Data from the Chinese Longitudinal Healthy Longevity Survey



Low-density lipoprotein cholesterol (LDL-C) is a risk factor for survival in middle-aged individuals, but conflicting evidence exists on the relationship between LDL-C and all-cause mortality among the elderly. The goal of this study was to assess the relationship between LDL-C and all-cause mortality among Chinese oldest old (aged 80 and older) in a prospective cohort study.


LDL-C concentration was measured at baseline and all-cause mortality was calculated over a 3-year period. Multiple statistical models were used to adjust for demographic and biological covariates.


During three years of follow-up, 447 of 935 participants died, and the overall all-cause mortality was 49.8%. Each 1 mmol/L increase of LDL-C concentration corresponded to a 19% decrease in 3-year all-cause mortality (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.71–0.92). The crude HR for abnormally higher LDL-C concentration (≥3.37 mmol/L) was 0.65 (0.41–1.03); and the adjusted HR was statistically significant around 0.60 (0.37–0.95) when adjusted for different sets of confounding factors. Results of sensitivity analysis also showed a significant association between higher LDL-C and lower mortality risk.


Among the Chinese oldest old, higher LDL-C level was associated with lower risk of all-cause mortality. Our findings suggested the necessity of re-evaluating the optimal level of LDL-C among the oldest old.

Keywords: LDL-C, mortality, oldest old, epidemiology, China



Prof. Marcia Angell, Harvard: “We certainly are in a health care crisis, ... If we had set out to design the worst system that we could imagine, we couldn't have imagined one as bad as we have.” Her excellent 77 minute lecture on pharma http://www.youtube.com/watch?v=ZqKY6Gr6D3Q