https://doi.org/10.1089/met.2021.0042

https://pubmed.ncbi.nlm.nih.gov/34918971

Abstract

Background: The objective of this open-label pilot study was to investigate the efficacy of a very-low-carbohydrate ketogenic diet (VLCKD), known as Nic's Ketogenic Diet, for 140 days on cardiometabolic markers in healthy adults with mildly elevated low-density lipoprotein cholesterol (LDL-C). Methods: Study assessments were conducted at Day 0, 28, 56, 70, 84, 112, and 140, and weight and blood pressure (BP) were measured and fasting blood was collected for analysis of plasma lipids. A DEXA scan was performed and body mass index recorded on Day 0, 70, and 140. Blood glucose, inflammatory, and thyroid markers were measured on Day 0 and 140. Compliance was assessed using weekly 3-day food records and daily blood glucose and ketone monitoring. Results: The results showed that body fat percentage decreased by 2.25% and 4.41% at Day 70 and 140, respectively (P  ≤ 0.012). Significant reductions in android, gynoid, and android/gynoid fat ratio and increases in muscle mass occurred by Day 70 and 140. Total cholesterol, LDL-C, and high-density lipoprotein cholesterol were increased and systolic BP and glycated hemoglobin (HbA1c) were decreased at Day 140 (P  < 0.05). Following this VLCKD for 140 days was found to be safe and was well tolerated. Conclusion: The VLCKD showed beneficial changes in body composition and cardiometabolic markers in eutrophic and overweight participants in a 140-day study suggesting a future role for this diet in populations at cardiovascular disease risk. Future research with larger sample size in a randomized double blind clinical trial is warranted to confirm these results. Clinical Trial Registration number: NCT04195594.

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Open Access: True

Authors: Nikolaos Tzenios - Erin D. Lewis - David C. Crowley - Mohamad Chahine - Malkanthi Evans -

Additional links:

https://doi.org/10.1089/met.2021.0042

“The American College of Cardiology/American Heart Association/Multisociety cholesterol guide- lines recommend adding a nonstatin if the low- density lipoprotein cholesterol (LDL-C) remains ≥70 mg/ dL in patients with high-risk atherosclerotic cardiovas- cular disease ASCVD,1 effectively creating a target of <70 mg/dL. The 2019 European Society of Cardiology/ European Atherosclerosis Society Dyslipidemia Guide- lines go further and recommend an LDL-C goal of <55 mg/dL for patients with very high-risk ASCVD and to consider an even lower goal of <40 mg/dL for patients with multiple cardiovascular events within 2 years despite optimal statin therapy.2 The advent of PCSK9 inhibition allows many patients to achieve even lower LDL-C levels. For example, evolocumab lowered LDL-C by 59% when added to statin therapy in the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhi- bition in Subjects With Elevated Risk), reducing LDL-C from a median of 93 mg/dL to 30 mg/dL.3 Nevertheless, a key question is whether there is evidence of continued clinical benefit with lowering LDL-C below 40 mg/dL…

Over the last 2 decades, we have seen the guide- lines shift to lower and lower LDL-C goals on the basis of clinical trials demonstrating that lower is better. The European Society of Cardiology/European Atheroscle- rosis Society Dyslipidemia Guidelines have selected an LDL-C goal of <40 mg/dL as the next step in this pro- gression. Previous clinical trials have proven that such levels are safe,3 and we have demonstrated in this study that there is continued effectiveness even below 40 mg/ dL in patients with high-risk ASCVD.

In conclusion, these data support the European Soci- ety of Cardiology/European Atherosclerosis Society Dyslipidemia Guidelines recommendations and suggest that lowering LDL-C well below 40 mg/dL in a wider range of patients with ASCVD would further lower car- diovascular risk.“

https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.056536?download=true

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7585909/

Abstract

Aim: The association between small dense low-density lipoprotein cholesterol (sdLDL-C) levels and carotid intimal medial thickness (cIMT) progression has not been evaluated fully. We assessed specialized lipoproteins, including sdLDL-C, with regard to cIMT progression in a prospective observational study in Japan.

Methods: Plasma total cholesterol, direct LDL-C, sdLDL-C, LDL-triglycerides (LDL-TG), high-density lipoprotein cholesterol (HDL-C), HDL2-C, HDL3-C, triglycerides, Lp(a), and adiponectin were measured in 2,030 men and women (median age 59 years, free of cardiovascular disease (CVD) and off cholesterol lowering medication). At both baseline and after a five-year follow-up, cIMT was assessed. Univariate, multivariate regression, and least square analyses were performed to examine the relationships between direct LDL-C, sdLDL-C, and other lipoproteins with cIMT progression.

Results: The median cIMT at baseline was 0.63 mm and five-year progression was 0.18 mm. After adjustment for standard CVD risk factors, including age, gender, systolic blood pressure, total cholesterol, HDL-C, smoking, diabetes, and hypertension treatment, only direct LDL-C, sdLDL-C, and the sdLDL-C/LDL-C ratio were associated with cIMT progression. ***Even in subjects with direct LDL-C < 100 mg/dL, who were considered at low CVD risk, elevated sdLDL-C were associated with cIMT progression (***P for trend = 0.009) in a model with established CVD risk factors, although the sdLDL-C/LDL-C ratio did not. Those correlations did not change by including triglycerides as a controlling factor or excluding premenopausal women from the analyzed population.

Conclusions: Small dense LDL-C has a stronger relationship with cIMT progression than LDL-C does; therefore, measuring sdLDL-C may allow for the formulation of optimal therapy for CVD prevention.

rticle Open Access Published: 11 November 2021

https://www.nature.com/articles/s41598-021-01738-w

Association between low density lipoprotein cholesterol and all-cause mortality: results from the NHANES 1999–2014

Ya Liu, Fubin Liu, […]Fengju Song Scientific Reports volume 11, Article number: 22111 (2021) Cite this article

Metrics details Abstract The association between low density lipoprotein cholesterol (LDL-C) and all-cause mortality has been examined in many studies. However, inconsistent results and limitations still exist. We used the 1999–2014 National Health and Nutrition Examination Survey (NHANES) data with 19,034 people to assess the association between LDL-C level and all-cause mortality. All participants were followed up until 2015 except those younger than 18 years old, after excluding those who died within three years of follow-up, a total of 1619 deaths among 19,034 people were included in the analysis. In the age-adjusted model (model 1), it was found that the lowest LDL-C group had a higher risk of all-cause mortality (HR 1.708 [1.432–2.037]) than LDL-C 100–129 mg/dL as a reference group. The crude-adjusted model (model 2) suggests that people with the lowest level of LDL-C had 1.600 (95% CI [1.325–1.932]) times the odds compared with the reference group, after adjusting for age, sex, race, marital status, education level, smoking status, body mass index (BMI). In the fully-adjusted model (model 3), people with the lowest level of LDL-C had 1.373 (95% CI [1.130–1.668]) times the odds compared with the reference group, after additionally adjusting for hypertension, diabetes, cardiovascular disease, cancer based on model 2. The results from restricted cubic spine (RCS) curve showed that when the LDL-C concentration (130 mg/dL) was used as the reference, there is a U-shaped relationship between LDL-C level and all-cause mortality. In conclusion, we found that low level of LDL-C is associated with higher risk of all-cause mortality. The observed association persisted after adjusting for potential confounders. Further studies are warranted to determine the causal relationship between LDL-C level and all-cause mortality

Low−/high-density lipoprotein cholesterol ratio and carotid plaques in patients with coronary heart disease: a Chinese cohort study

Zhu Li, Qi Cheng, […]Chunquan Yu Lipids in Health and Disease volume 20, Article number: 144 (2021) Cite this article

Metrics details Abstract

Background Evidence on the relationship between the low−/high-density lipoprotein cholesterol ratio (LDL-C/HDL-C) and carotid plaques remains limited. This study aimed to examine the association between LDL-C/HDL-C and carotid plaques in participants with coronary heart disease (CHD) and to further explore the extent to which a healthy lifestyle reduces the risk of LDL-C/HDL-C-related carotid plaques.

Methods This large-scale and multi-centre retrospective study included 9426 CHD patients (aged 35–75 years) between January 1, 2014 and September 30, 2020. The LDL-C/HDL-C values were converted to the following tertiles: lowest (< 2.15), middle (2.15–3), and highest (> 3). Healthy lifestyle-related factors referred to whether or not the participant was a non-smoker and non-drinker. Participants were divided into an unfavourable group (those who did not adhere to healthy lifestyle factors), intermediate (only one unhealthy factor), and favourable (neither of the two unhealthy factors). Logistic regression was used for statistical analyses.

Results Of the 9426 participants, 6989 (74.15%) CHD patients had carotid plaques. After adjustment for confounders, each unit increase in the LDL-C/HDL-C was significantly associated with carotid plaques (OR: 1.61; 95%CI: 1.43–1.84; P <  0.001). Multivariate logistic regression revealed that carotid plaques risk for the highest tertile (> 3) was 1.18 times that of the lowest quartile (< 2.15). Compared with an unfavourable lifestyle, an intermediate or a favourable lifestyle was associated with a significant 30% (OR: 0.70; 95%CI: 0.64–0.78; P <  0.001) or 67% (OR: 0.33; 95%CI: 0.29–0.37; P <  0.001) reduction in carotid plaques risk, respectively, among CHD patients with high LDL-C/HDL-C. There were significantly additive and multiplicative interactions between lifestyle and LDL-C/HDL-C with regards to carotid plaques.

Conclusion A high LDL-C/HDL-C is associated with a risk of carotid plaques developing in CHD patients. Adhering to a healthy lifestyle has additive beneficial effects on reducing the risk of carotid plaques, especially in relation to the highest LDL-C/HDL-C.

Research Open Access Published: 12 September 2021 Low density lipoprotein cholesterol and all-cause mortality rate: findings from a study on Japanese community-dwelling persons

Ryuichi Kawamoto, Asuka Kikuchi, […]Teru Kumagi Lipids in Health and Disease volume 20, Article number: 105 (2021) Cite this article

Metrics details

https://lipidworld.biomedcentral.com/articles/10.1186/s12944-021-01533-6

Abstract

Background Low-density lipoprotein cholesterol (LDL-C) independently impacts aging-related health outcomes and plays a critical role in cardiovascular diseases (CVDs). However, there are limited predictive data on all-cause mortality, especially for the Japanese community population. In this study, it was examined whether LDL-C is related to survival prognosis based on 7 or 10 years of follow-up.

Methods Participants included 1610 men (63 ± 14 years old) and 2074 women (65 ± 12 years old) who participated in the Nomura cohort study conducted in 2002 (first cohort) and 2014 (second cohort) and who continued throughout the follow-up periods (follow-up rates: 94.8 and 98.0%). Adjusted relative risk estimates were obtained for all-cause mortality using a basic resident register. The data were analyzed by a Cox regression with the time variable defined as the length between the age at the time of recruitment and that at the end of the study (the age of death or censoring), and risk factors including gender, age, body mass index (BMI), presence of diabetes, lipid levels, renal function, serum uric acid levels, blood pressure, and history of smoking, drinking, and CVD.

Results Of the 3684 participants, 326 (8.8%) were confirmed to be deceased. Of these, 180 were men (11.2% of all men) and 146 were women (7.0% of all women). Lower LDL-C levels, gender (male), older age, BMI under 18.5 kg/m2, and the presence of diabetes were significant predictors for all-cause mortality. Compared with individuals with LDL-C levels of 144 mg/dL or higher, the multivariable-adjusted Hazard ratio (and 95% confidence interval) for all-cause mortality was 2.54 (1.58–4.07) for those with LDL-C levels below 70 mg/dL, 1.71 (1.15–2.54) for those with LDL-C levels between 70 mg/dL and 92 mg/dL, and 1.21 (0.87–1.68) for those with LDL-C levels between 93 mg/dL and 143 mg/dL. This association was particularly significant among participants who were male (P for interaction = 0.039) and had CKD (P for interaction = 0.015).

Conclusions There is an inverse relationship between LDL-C lev

https://doi.org/10.1177/17085381211035282

https://pubmed.ncbi.nlm.nih.gov/34311590

Abstract

BACKGROUND

It is indicated that Low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (LDL-C/HDL-C ratio) has greater predictive value for thickened carotid intima-media thickness (CIMT) comparing with classic lipid parameters. However, there have been few reports about their association in general Chinese population.

METHOD

We included a total of 1220 CIMT participants and 2440 matched controls, who had ultrasonography of carotid artery during 2009 and 2016. Univariate and multivariate logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for thickened CIMT risk associated with LDL-C/HDL-C ratio.

RESULT

In the univariate logistic regression model, there was significant association between LDL-C/HDL-C ratio and thickened CIMT (Q4 vs. Q1, OR = 1.94, 95% CI: 1.60-2.36,p trend < 0.05). After adjusting for potential covariates, LDL-C/HDL-C ratio remained significantly associated with thickened CIMT (Q4 vs. Q1, OR = 1.81, 95% CI: 1.41-2.34,p trend < 0.001, ≥3.05 v.s. <3.05, OR = 1.66, 95% CI: 1.37-2.02). In subgroup analyses, the association between LDL-C/HDL-C ratio and thickened CIMT remained significant in the subgroups stratified by sex, impaired fasting glucose (IFG), hypertension, and fatty liver disease but only remained significant in the subgroups of ≥45 years (OR = 2.01, 95% CI: 1.46-2.76,P trend*<* 0.05), BMI ≥24 (kg/m^(2) ) (OR = 2.22, 95% CI = 1.63-3.03, Ptrend < 0.05) and BMI ≥25 (kg/m^(2) ) (OR = 2.50, 95% CI: 1.76-3.54,P trend < 0.05), dyslipidemia (OR = 3.28, 95% CI: 1.83-5,85,P trend*<* 0.001), and without periodontitis (OR = 2.08, 95% CI: 1.54-2.81 , Ptrend < 0.05) comparing Q4 to Q1. Similar results were observed in the subgroup analyses for LDL-C/HDL-C ratio ≥3.05 v.s. <3.05 except for the age stratification.

CONCLUSION

High LDL-C/HDL-C ratio could significantly increase the risk of thickened CIMT independent of gender, IFG, hypertension, and fatty liver disease in general Chinese population.

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Open Access: False

Authors: Zhucheng Zhang - Yang Liu - Yanyan Zhang - Pei Qin - Ping Zhao - Changyi Wang - Li W

Fish Physiol Biochem

. 2021 Jul 29. doi: 10.1007/s10695-021-00965-2. Online ahead of print.

Metabolic responses of Chinese perch (Siniperca chuatsi) to different levels of dietary carbohydrate

Yanpeng Zhang 1 2, Xu-Fang Liang 3 4, Shan He 1 2, Jie Wang 1 2, Ling Li 1 2, Zhen Zhang 1 2, Jiao Li 1 2, Xu Chen 1 2, Lu Li 1 2, Muhammad Shoaib Alam 1 [2](https://pubmed.ncbi.nlm.nih.gov/34324096/#affi

https://doi.org/10.1161/JAHA.120.019140

https://pubmed.ncbi.nlm.nih.gov/33586462

Abstract

Background Elevated plasma levels of direct low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C), low-density lipoprotein (LDL) triglycerides, triglycerides, triglyceride-rich lipoprotein cholesterol, remnant lipoprotein particle cholesterol, and lipoprotein(a) have all been associated with incident atherosclerotic cardiovascular disease (ASCVD). Our goal was to assess which parameters were most strongly associated with ASCVD risk. Methods and Results Plasma total cholesterol, triglycerides, high-density lipoprotein cholesterol, direct LDL-C, sdLDL-C, LDL triglycerides, remnant lipoprotein particle cholesterol, triglyceride-rich lipoprotein cholesterol, and lipoprotein(a) were measured using standardized automated analysis (coefficients of variation, <5.0%) in samples from 3094 fasting subjects free of ASCVD. Of these subjects, 20.2% developed ASCVD over 16 years. On univariate analysis, all ASCVD risk factors were significantly associated with incident ASCVD, as well as the following specialized lipoprotein parameters: sdLDL-C, LDL triglycerides, triglycerides, triglyceride-rich lipoprotein cholesterol, remnant lipoprotein particle cholesterol, and direct LDL-C. Only sdLDL-C, direct LDL-C, and lipoprotein(a) were significant on multivariate analysis and net reclassification after adjustment for standard risk factors (age, sex, hypertension, diabetes mellitus, smoking, total cholesterol, and high-density lipoprotein cholesterol). Using the pooled cohort equation, many specialized lipoprotein parameters individually added significant information, but no parameter added significant information once sdLDL-C (hazard ratio, 1.42,P <0.0001) was in the model. These results for sdLDL-C were confirmed by adjusted discordance analysis versus calculated non-high-density lipoprotein cholesterol, in contrast to LDL triglycerides. Conclusions sdLDL-C, direct LDL-C, and lipoprotein(a) all contributed significantly to ASCVD risk on multivariate analysis, but no parameter added significant risk information to the pooled cohort equation once sdLDL-C was in the model. Our data indicate that small dense LDL is the most atherogenic lipoprotein parameter.

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Open Access: Tru

BMC Med

. 2021 Jun 16;19(1):142. doi: 10.1186/s12916-021-02014-4.

The risk of ischemic stroke and hemorrhagic stroke in Chinese adults with low-density lipoprotein cholesterol concentrations < 70 mg/dL

Zhijun Wu # 1, Zhe Huang # 2, Alice H Lichtenstein 3, Yesong Liu 4, Shuohua Chen 5, Yao Jin 1, Muzi Na 6, Le Bao 7, Shouling Wu 8, Xiang Gao 9Affiliations expand

• PMID: 34130689
• DOI: 10.1186/s12916-021-02014-4

Abstract

Background: The risk of stroke in individuals with very low low-density lipoprotein cholesterol (LDL-C) concentrations remains high. We sought to prioritize predictive risk factors for stroke in Chinese participants with LDL-C concentrations < 70 mg/dL using a survival conditional inference tree, a machine learning method.

Methods: The training dataset included 9327 individuals with LDL-C concentrations < 70 mg/dL who wer

“American physicians are now treating dyslipidemia according to a fifth iteration of national guidelines for the use of lipid-lowering therapies [1]. These guidelines are developed with considerable care and deliberation and are, by design, as evidence-based as possible. Specific recommendations are made in order to safely and optimally use pharmacologic interventions to maximize clinical benefit. Since publication of the first Adult Treatment Panel for the Management of Blood Cholesterol, over three decades have elapsed. The association of serum low-density lipoprotein cholesterol (LDL-C) with atherosclerotic cardiovascular disease is one of the most extensively studied and highly established issues in all of medicine [2].

There is unequivocal evidence that the use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) significantly reduce ASCVD events (myocardial infarction [MI], stroke, need for revascularization, and mortality) in both primary and secondary prevention settings [3,4]. Moreover, statin therapy is just as beneficial in the elderly with established vascular disease as it is in younger groups of patients [5]. Higher dose statin therapy with greater LDL-C reduction provides additional ASCVD event rate reduction compared to lower dose statin therapy [6]. Other LDL-C lowering agents such as ezetimibe [7] and the proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies [8,9] provide incremental risk reduction when used as adjuvant therapies to background statin use in high risk patients. Despite the great specificity and clarity of guidelines both in the US and in other regions of the world, the appropriate use of lipid-lowering therapies (LLT) is disappointingly and frustratingly low. Given the incontrovertible strength of evidence, why has this become such a perennial, lasting observation?

… Perhaps it is time to change the view of LDL-C. LDL-C is the end product of lipoprotein metabolism. Its precursors, very low-density lipoprotein and interediate density lipoprotein, are reservoirs of oxidizable substrate (triglycerides, fatty acids). LDL is highly concentrated with cholesterol. The histologic components of arterial walls cannot catabolize cholesterol. The assumption is that LDL distributes this cholesterol as a vital regulator of cell membrane fluidity or is an important donor of cholesterol to steroidogenic tissues. All somatic cells have the capacity to produce their own cholesterol. When

http://www.onlinejacc.org/content/59/13_Supplement/E1622

Paul Michael Lavigne, Haseeb Jafri and Richard Karas

Background

We recently reported, in a meta-analysis of statin trials, a strong association between low concentrations of low-density lipoprotein cholesterol (LDL-C) and incident cancer risk. Interpretation of these data has been a point of significant debate. At issue is whether low LDL-C concentration signifies a predisposition to cancer development, or rather results from the presence of even a subclinical neoplastic process (reverse causality). Of pivotal importance to this debate is the duration of low LDL-C levels prior to cancer diagnosis. We explored this controversy using data from the Framingham Heart Study Offspring Cohort to assess the trend of LDL-C for an extended period prior to cancer diagnosis.

Methods

Incident cancer cases and control subjects (propensity score matched for age, gender, diabetes, tobacco use, blood pressure, and body mass index) without history of lipid-lowering therapy, were followed for 4 time points prior to cancer diagnosis. Linear mixed model regression analyses delineated the relationship of LDL-C between cancer and cancer-free participants over time.

Results

201 incident cancer cases and 402 matched controls were identified. LDL-C values were lower in cancer subjects than matched controls at each point of assessment throughout an average of 18.7 years prior to diagnosis (F = 4.32, p = .038). The trend for lower LDL-C in cancer patients compared with control subjects was consistent throughout the duration of the study (F = .14, p = .968 for differences between time points). These findings did not change when controlling for high-density lipoprotein cholesterol levels.

Conclusion

Our analysis demonstrates an inverse association between LDL-C and cancer extending over 18 years prior to diagnosis. This is inconsistent with the reverse causality hypothesis, but rather supports that low levels of LDL-C can predate cancer diagnosis by decades. While not itself indicative of an etiologic role for LDL-C in predisposition to cancer, these findings underscore the need for further study in this area, particularly in light of current LDL-C lowering guidelines.

This is the profile that Dave Feldman has put forward as likely being a healthy profile. It appears it has already been looked at in a cohort study.

https://www.ncbi.nlm.nih.gov/pubmed/11176761 ; https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/647239 ; https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/647239/ioi00156.pdf

Abstract

Background A high triglyceride (TG)–low high-density lipoprotein cholesterol (HDL-C) level (TG ≥1.60 mmol/L [≥142 mg/dL] and HDL-C ≤1.18 mmol/L [≤46 mg/dL]) is associated with a high risk of ischemic heart disease (IHD), whereas a low TG–high HDL-C level (TG ≤1.09 [≤97 mg/dL] and HDL-C ≥1.48 mmol/L [≥57 mg/dL]) is associated with a low risk. Conventional risk factors tend to coexist with high TG–low HDL-C levels. We tested the hypothesis that subjects with conventional risk factors would still have a low risk of IHD if they had low TG–high HDL-C levels.

Methods Observational cohort study of 2906 men aged 53 to 74 years free of IHD at baseline.

Results During 8 years, 229 subjects developed IHD. Stratified by conventional risk factors—low-density lipoprotein cholesterol level (≤4.40 mmol/L or >4.40 mmol/L [≤170 mg/dL or >170 mg/dL] [median value]), hypertensive status (blood pressure >150/100 mm Hg or taking medication), level of physical activity (>4 h/wk or ≤4 h/wk), and smoking status (nonsmokers vs smokers)—the incidence in men with high TG–low HDL-C levels was 9.8% to 12.2% in the low-risk and 12.2% to 16.4% in the high-risk strata; the corresponding values in men with low TG–high HDL-C concentrations were 4.0% to 5.1% and 3.7% to 5.3%, respectively. Based on an estimate of attributable risk, 35% of IHD might have been prevented if all subjects had had low TG–high HDL-C levels.

Conclusion Men with conventional risk factors for IHD have a low risk of IHD if they have low TG–high HDL-C levels.

-------

Main results

The major new finding from this study was that men with major classic risk factors of IHD such as a high LDL-C level, hypertension, low physical activity, and smoking2,[3](https://jamanetwork.com/journals/jamainternalme

OKay, I've done some blood tests and, without a doubt, Pterostilbene raises LDL-C. I went from 113 - 163 in three months. With that said, I did a bit of research and found that pterostilbene does not bind to sirtuin 1. Sirtuin 1 activators are expected to improve lipid management . But I still do not understand WHY this happens? How is it that Pterostilbene raises LDL, I do not understand this path. Can someone explain this to me?

But...but, it's the BAD cholesterol!

https://www.frontiersin.org/articles/10.3389/fneur.2018.00952/full?fbclid=IwAR3n2fK8vs3HL5lhsXgW-y4u2uTo54koCx_Ai1dZpNWE8ES8-vRRI98W5AY

Edit: Fix link

https://www.frontiersin.org/articles/10.3389/fneur.2018.00952/full?fbclid=IwAR3n2fK8vs3HL5lhsXgW-y4u2uTo54koCx_Ai1dZpNWE8ES8-vRRI98W5AY

The study did adjust for age, sex, years of education, APOE-ε4 genotype, BMI, depression, diabetes, hyprtension and stroke.

If statins were not an adjustment, then that is an obvious suspect for cognitive decline.

Many of the hyposthesis below are not exclusive....

Although the exact biological mechanism of LDL-C's potential protective effect is still unknown, we conjecture that one possibility is that high LDL-C might indicate a good nutritional status or health condition.

Lower cholesterol has been found to be associated with a higher mortality in the elderly, and it may accompany malnutrition, chronic diseases and cancer, which in turn may positively associate with cognitive decline.

On the other hand, because cholesterol is a major component of the brain, it is possible that decreasing cholesterol levels in the elderly is associated with cerebral atrophy, a typical anatomic syndrome of dementia.

Another speculation is that high LDL-C could reduce neurons' impairments or facilitate compensatory repair of injured neurons. The inhibitions of dendrite outgrowth and synaptogenesis, and the acceleration of neurodegeneration have been observed when neurons was a short of cellular cholesterol or cholesterol supply.

Besides, cholesterol plays an important role in the synthesis, transportation and metabolism of steroid hormones as well as lipid-soluble vitamins, both of which have an impact on synaptic integrity and neurotransmission.

https://www.mdpi.com/2077-0383/8/10/1571/htm

Abstract: We aimed to test the association between low-density lipoprotein cholesterol (LDL-C) and cardiovascular disease (CVD), cancer, and all-cause mortality in non-statin users. A total of 347,971 subjects in Kangbuk Samsung Health Study (KSHS.57.4% men, mean follow up: 5.64 ± 3.27 years) were tested. To validate these associations, we analyzed data from another cohort (Korean genome and epidemiology study, KoGES, 182,943 subjects). All subjects treated with any lipid-lowering therapy and who died during the first 3 years of follow up were excluded. Five groups were defined according to baseline LDL-C concentration (<70, 70–99, 100–129, 130–159, ≥160 mg/dL). A total of 2028 deaths occurred during follow-up in KSHS. The lowest LDL-C group (LDL < 70 mg/dL) had a higher risk of all-cause mortality (HR 1.95, 1.55–2.47), CVD mortality (HR 2.02, 1.11–3.64), and cancer mortality (HR 2.06, 1.46–2.90) compared to the reference group (LDL 120–139 mg/dL). In the validation cohort, 2338 deaths occurred during follow-up. The lowest LDL-C group (LDL < 70 mg/dL) had a higher risk of all-cause mortality (HR 1.81, 1.44–2.28) compared to the reference group. Low levels of LDL-C concentration are strongly and independently associated with increased risk of cancer, CVD, and all-cause mortality. These findings suggest that more attention is needed for subjects with no statin-induced decrease in LDL-C concentrations. Keywords: low density lipoprotein cholesterol; mortality; cancer; cardiovascular disease