Recent Research/Data Thread...

[nothuman]

19 nors make you crazy?!

Maybe 5mg prozac is a solution!

1.7. Stimulation of allopregnanolone biosynthesis by antidepressants​

The selective serotonin reuptake inhibitor (SSRI) fluoxetine has widespread use in medicine and is one of the antidepressant drugs that are most commonly used as a positive control during preclinical experiments. This is because it consistently decreases immobility time by increasing swimming in the FST (as originally described by Detke and Lucki, 1995), which is a parameter related to serotonergicmechanisms. Interestingly, the first evidence of a drug-induced modulation of brain allopregnanolone in the context of depression was provided by Uzunov and colleagues in the following year, and also had fluoxetine as the main comparable substance (Uzunov et al., 1996). In this report, a single injection of fluoxetine or paroxetine increased allopregnanolone levels in corticolimbic brain regions of rats for at least 2 h after treatment. These observations sparked interest regarding the capability of other SSRIs to act as selective brain steroidogenic stimulants (SBSSs), a possibility that was further supported by subsequent in vitro experiments that demonstrated the increased activity of neurosteroidogenic enzymes associated with fluoxetine, paroxetine and sertraline (Griffin and Mellon, 1999). Furthermore, in vivo increases in cerebrocortical allopregnanolone levels induced by numerous SSRIs were later reported after a three-week treatment with paroxetine in male mice (Nechmad et al., 2003) and with fluoxetine, desipramine, sertraline and venlafaxine in olfactory bulbectomized male rats (Uzunova et al., 2004). It is worth mentioning that other classes of drugs have also been reported to increase brain allopregnanolone levels, namely the atypical antipsychotics clozapineand olanzapine (Marx et al., 2006, 2003) and the benzodiazepines midazolam (Qiu et al., 2015) and estazolam (Xu et al., 2018b). On the other hand, a single injection of the tricyclic antidepressantimipramine at behaviorally active doses has consistently been shown not to change brain allopregnanolone levels after 30 min (Pinna et al., 2003, 2004b; Uzunov et al., 1996), probably due to its reported lack of effect on neurosteroidogenic enzymes (Griffin and Mellon, 1999). This is relevant because it is one of the lines of evidence that indicates that not all antidepressants act by this mechanism and that allopregnanolone upregulation is not simply a side effect of monoamine reuptake, but rather a direct effect of SSRIs like fluoxetine. The precise mechanism by which fluoxetine increases brain allopregnanolone levels has not yet been fully determined, but early evidence pointed to the direct activation of the 3α-HSD enzyme which converts 5α-dihydroprogesterone into allopregnanolone (Griffin and Mellon, 1999). This finding could not be replicated, however (Trauger et al., 2002), and more recent evidence indicates that, at least in female rats, the inhibition of a steroid microsomal dehidrogenase may consist in a more robust mechanism by avoiding allopregnanolone oxidation to 5α-dihydroprogesterone (Fry et al., 2014).
Importantly, fluoxetine has been shown to increase brain neurosteroid content at doses remarkably lower than those needed to inhibit serotonin reuptake, as determined by ex vivo uptake measurements on brain slices or in vivo serotonin detection by microdialysis(Devall et al., 2015; Pinna et al., 2003, 2004b). Thus, these findings granted further support for a direct action of fluoxetine on steroidogenesis, as outlined above. Additionally, they raised the question of whether the administration of fluoxetine at such low doses is capable of eliciting a similar antidepressant-like action by upregulating brain allopregnanolone while being devoid of any significant serotonergic action. Early studies have failed to detect an antidepressant-like effect in the mice FST with low-range doses (1 and 5 mg/kg) (Khisti et al., 2000; Khisti and Chopde, 2000), but a later work achieved this goal in rats using doses as low as 1 and 2 mg/kg (Molina-Hernández et al., 2005). This indicates that a possible antidepressant-like effect of non-SSRI doses of fluoxetine hovers just over the detectable threshold in the FST, and different species or subtle modifications in the protocol might affect its results.
Given the difficulty generated by such a low and narrow dose window, most of the studies that investigated the antidepressant-like action of allopregnanolone opted to directly administer the neurosteroid instead of upregulating its levels by using drugs that act indirectly and might exert the same target effect by confounding mechanisms.

Reference: The role of allopregnanolone in depressive-like behaviors: Focus on neurotrophic proteins​

Pregnenolone supplementation raises allopregnanolone as well. I’d use that instead.

 

[danieltx]

Omega 3 Supplements Slow Biological Aging

This article is behind a paywall so what's quoted is all that's visible without a subscription.

https://nature.com/articles/d41586-025-00355-1

Clinician-scientist Heike Bischoff-Ferrari and geroscientist Steve Horvath take omega-3 and vitamin D supplements every day to prevent ageing-related health issues. “I do this every morning with my coffee,” says Horvath, who is based at biotechnology company Altos Labs in Cambridge, UK. “I practise what we publish.”

In Nature Aging today, the pair are co-authors on a study that showed that these supplements over a three-year period slowed biological ageing by three to four months, particularly when combined with exercise. Biological ageing is measured at a molecular level; people of the same chronological age can have faster or slower age-related decline depending on their health.

Three to four months’ slowing of biological ageing sounds small, but this can translate to important public-health benefits such as a reduction in the prevalence of some age-related health conditions, says Bischoff-Ferrari at the University of Basel in Switzerland.

The study analysed data from the DO-HEALTH trial on the effects of supplements and exercise in older people, that took place across five European countries from 2012 to 2014. The researchers reviewed data on more than 700 people aged 70 or over who were given either a placebo or omega-3, vitamin D and exercise alone or in combination. All the participants were from Switzerland and around half were healthy, with no major chronic illnesses or disabilities.

Blood samples taken from participants at the start and end of the study were analysed using four biological clocks. These measure the extent of biological ageing on the basis of additions and deletions of methyl groups to the DNA.

“The use of multiple DNA methylation clocks is a strength, as different clocks capture distinct aspects of biological ageing,” says Luigi Fontana, a biogerontologist at the University of Sydney in Australia.

Stronger together​

One of those clocks, called PhenoAge, showed that older people avoided several months of biological ageing over 3 years by taking 1 gram of polyunsaturated omega-3 fatty acids, derived from algae, with additive benefits from taking vitamin D (2,000 international units per day) and engaging in 30 minutes of exercise 3 times a week. Together, the 3 treatments reduced biological ageing by 2.9–3.8 months.

On its own, omega-3 slowed biological ageing in three of the epigenetic clocks the researchers used.

 

[Stewie]

Omega 3 Supplements Slow Biological Aging

This article is behind a paywall so what's quoted is all that's visible without a subscription.

https://nature.com/articles/d41586-025-00355-1

Post 36 on the previous page has the full literature.

Recent Research/Data Thread...

Yes, I am very similar but Primo also hits LDL for me. I have bloods soon on 350mg Test/EQ to measure lipids and E2. Please let me know how this goes. Interested in equipoise and lipids for sure. I will say Primo hits E2 but EQ is a hammer did my E2.

www.professionalmuscle.com

 

[Jerry5000]

I was taking Gorilla Mind's Omega-3 Elixir daily for a few months. From all the research I did it seemed like a good product. Anyone else use this?

 

[Stewie]

Endocrinology, Volume 166, Issue 2, February 2025, bqae165,

GLP-1 and Its Analogs: Does Sex Matter?


●Abstract
While obesity and diabetes are prevalent in both men and women, some aspects of these diseases differ by sex. A new blockbuster class of therapeutics, glucagon-like peptide 1 (GLP-1) analogs (eg, semaglutide), shows promise at curbing both diseases. This review addresses the topic of sex differences in the endogenous and therapeutic actions of GLP-1 and its analogs. Work on sex differences in human studies and animal research is reviewed. Preclinical data on the mechanisms of potential sex differences in the endogenous GLP-1 system as well as the therapeutic effect of GLP-1 analogs, focusing on the effects of the drugs on the brain and behavior relating to appetite and metabolism, are highlighted. Moreover, recent clinical evidence of sex differences in the therapeutic effects of GLP-1 analogs in obesity, diabetes, and cardiovascular disease are discussed. Lastly, we review evidence for the role of GLP-1 analogs in mood and reproductive function, with particular attention to sex differences. Overall, while we did not find evidence for many qualitative sex differences in the therapeutic effect of clinically approved GLP-1 analogs, a growing body of literature highlights quantitative sex differences in the response to GLP-1 and its analogs as well as an interaction of these therapeutics with estrogens. What also clearly emerges is the paucity of data in female animal models or women in very basic aspects of the science of GLP-1—gaps that should be urgently mended, given the growing popularity of these medications, especially in women.

https://academic.oup.com/endo/article/166/2/bqae165/7931638

 

[Stewie]

First published: 19 November 2024
Anabolic Sensitivity in Healthy, Lean, Older Men Is Associated With Higher Expression of Amino Acid Sensors and mTORC1 Activators Compared to Young

●ABSTRACT
Background
Sarcopenia is thought to be underlined by age-associated anabolic resistance and dysregulation of intracellular signalling pathways. However, it is unclear whether these phenomena are driven by ageing per se or other confounding factors.

●Methods
Lean and healthy young (n = 10, 22 ± 3 years, BMI; 23.4 ± 0.8 kg/m2) and old men (n = 10, 70 ± 3 years, BMI; 22.7 ± 1.3 kg/m2) performed unilateral resistance exercise followed by intake of essential amino acids (EAA). Muscle biopsies were collected from the rested and the exercised leg before, immediately after and 60 and 180 min after EAA intake. Muscle samples were analysed for amino acid concentrations, muscle protein synthesis (MPS) and associated anabolic signalling.

●Results
Following exercise, peak plasma levels of EAA and leucine were similar between groups, but the area under the curve was ~11% and ~28% lower in Young (p < 0.01). Absolute levels of muscle EAA and leucine peaked 60 min after exercise, with ~15 and ~21% higher concentrations in the exercising leg (p < 0.01) but with no difference between groups. MPS increased in both the resting (~0.035%·h−1 to 0.056%·h−1, p < 0.05) and exercising leg (~0.035%·h−1 to 0.083%·h−1, p < 0.05) with no difference between groups. Phosphorylation of S6K1Thr389 increased to a similar extent in the exercising leg in both groups but was 2.8-fold higher in the resting leg of Old at the 60 min timepoint (p < 0.001). Phosphorylation of 4E-BP1Ser65 increased following EAA intake and exercise, but differences between legs were statistically different only at 180 min (p < 0.001). However, phosphorylation of this site was on average 78% greater across all timepoints in Old (p < 0.01). Phosphorylation of eEF2Thr56 was reduced (~66% and 39%) in the exercising leg at both timepoints after EAA intake and exercise, with no group differences (p < 0.05). However, phosphorylation at this site was reduced by ~27% also in the resting leg at 60 min, an effect that was only seen in Old (p < 0.01). Total levels of Rheb (~45%), LAT1 (~31%) and Rag B (~31%) were higher in Old (p < 0.001).

●Conclusion
Lean and healthy old men do not manifest AR as evidenced by potent increases in MPS and mTORC1 signalling following EAA intake and exercise. Maintained anabolic sensitivity with age appears to be a function of a compensatory increase in basal levels of proteins involved in anabolic signalling. Therefore, our results suggest that age per se does not appear to cause AR in human skeletal muscle.

https://onlinelibrary.wiley.com/doi/10.1002/jcsm.13613

 

[danieltx]

https://www.cnn.com/2025/02/09/health/belly-fat-liver-alcohol-wellness/index.html

3 health conditions increase risk of liver damage if you drink, study says​

Drinking alcohol if you have a large belly or diabetes more than doubles the risk of serious liver damage, while having high blood pressure and drinking nearly doubles the risk, a new study found.

That’s important news to consider this Super Bowl Sunday, said Dr. Andrew Freeman, director of cardiovascular prevention and wellness at National Jewish Health in Denver, Colorado, who was not involved in the study.

“People are going to do exactly what they shouldn’t do, and poison themselves during the Super Bowl,” Freeman said. “Particularly during big football games, people will eat things like hot dogs, sausage, bacon, pepperoni and ham — and these processed meats are in the same category as cigarettes for cancer risk.

“When you’re eating all these highly processed, high fat, high sugar foods, insulin goes into overdrive, which creates insulin resistance, then excess blood sugar, and then fatty liver,” Freeman added. “Then if you’re drinking on top of it, it just amplifies the risk.”

A waist measurement of 35 inches or more for women and 40 inches or more for men, which is often associated with obesity, is one of several cardiometabolic risk factors that also include high blood sugar and elevated blood pressure.

Nearly half of all Americans have high blood pressure, more than 1 in 3 have pre-diabetes, while about 40% of the population is considered obese, according to the US Centers for Disease Control and Prevention.

These health conditions contribute to a buildup of fat in the liver, experts say, which can then lead to fibrosis, or scarring of the liver.

“Most people don’t realize this, but before one develops diabetes, for example, they typically first develop fatty liver,” Freeman said. “It has to do with sugar dysregulation — when you have high blood sugars, your liver is storing fat to get rid of some of that sugar, and it’s that excess fat that impairs liver function.”

Separately, drinking damages liver cells trying to metabolize alcohol and can lead to additional fat buildup. The inflammation and scarring caused by excess fat may eventually lead to cirrhosis, which increases the risk of liver failure and liver cancer.

This double whammy of fatty deposits may be a reason behind the significant increase in liver scarring the study found among moderate to heavy drinkers with chronic conditions, said lead study author Dr. Brian Lee, an associate professor of clinical medicine at the University of Southern California’s Keck School of Medicine.

“The results identify a very high-risk segment of the population prone to liver disease and suggest that preexisting health issues may have a large impact on how alcohol affects the liver,” Lee said in a statement.

Just because a person may not have a big belly, high blood pressure or diabetes does not mean that it’s safe for people to heavily consume alcohol, Lee said.

“We know that alcohol is toxic to the liver and all heavy drinkers are at risk for advanced liver disease,” Lee said.

What is a ‘heavy’ drinker?​

The study, published recently in the journal of Clinical Gastroenterology and Hepatology, analyzed data from the National Health and Nutrition Examination Survey, a national government survey of nearly 41,000 people. Of those, over 2,200 were categorized as “heavy” drinkers.

In the study, women who drank more than 0.7 ounces (20 grams) or more a day and men who drank 1.05 ounces (30 grams) or more a day were defined as heavy drinkers.

.However, that amount of alcohol is typically considered to be “moderate” drinking, according to the CDC. A standard drink in the United States is defined as 0.6 ounces (14 grams) of pure liquor.

That’s equivalent to 5 ounces of wine with 12% alcohol, a 12-ounce can of beer that is 5% alcohol or 1.5 ounces (one shot) of liquor (80 proof) or distilled spirts. Most people don’t realize they are pouring drinks that far exceed those standards, experts say.

“If you look at what people drink with dinner or as a cocktail, they’re filling up their glass with three or four ounces,” Freeman said. “If a restaurant came out and poured you five ounces of wine, you’d complain that they didn’t fill your glass. People are probably drinking much more than they realize.”

An alarming number of new studies are finding that any amount of alcohol is dangerous to health. In January, then-US Surgeon General Dr. Vivek Murthy issued a strongly worded advisory about the link between alcohol and cancer.

“Alcohol is a well-established, preventable cause of cancer responsible for about 100,000 cases of cancer and 20,000 cancer deaths annually in the United States – greater than the 13,500 alcohol-associated traffic crash fatalities per year in the US – yet the majority of Americans are unaware of this risk,” Murthy said.

However, only 45% of Americans surveyed by the American Institute for Cancer Research in 2019 said they believed that drinking alcohol causes cancer, the new advisory notes.

How to cut back on alcohol​

One easy way is to substitute mocktails for alcohol, especially in a social setting where you want to feel part of the party. Some mocktails rely on manufactured non-alcoholic spirits, botanicals and bitters but others are simple mixtures of fruit juice, soda, and syrup, experts say.

If you find mocktails don’t satisfy your urges for alcohol, experts suggest using the SMART method to set attainable goals. The acronym stands for:

1. Specific: Set an achievable goal, such as cutting back on drinking three days a week. You can add days until you reach your final goal.

2. Measurable: How many drinks will you cut — and are you watching the size of your drink?

3. Achievable: Reduce the number of social engagements where alcohol is likely to be served during your move toward becoming alcohol free.

4. Relevant: Ask yourself how not drinking will help you with with life and health.

5. Time based: Set a reasonable time frame to reduce alcohol consumption.

“If you set a bar too high, you may fail, so it’s better to set smaller goals to achieve it,” Dr. Sanam Hafeez, a neuropsychologist based in New York City, told CNN in a prior interview.

To start, Hafeez noted, it’s good to be aware of what you’re already doing: “Nothing starts without an honest conversation with yourself.”

 

[Stewie]

Association studies can be noteworthy for more detailed future causative studies. If enough evidence warrants further investigations.

Oddly, my HDL-C has for the most part been highish +/- 50-65 mg/dL for as long as I can remember. I was diagnosed with stage 1 glaucoma and few years ago.

Nevertheless.

2025 Feb 4:bjo-2024-326062.
doi: 10.1136/bjo-2024-326062.

Associations between serum lipids and glaucoma: a cohort study of 400 229 UK Biobank participants

Abstract
Purpose: To examine the associations of commonly-used serum lipid measures (high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and triglycerides (TG)) with glaucoma.

Methods: This prospective cohort study included 400 229 participants from the UK Biobank. Cox regression and restricted cubic spline models and polygenic risk scores were employed to investigate the associations between serum lipids and glaucoma.

Results: Over a mean follow-up of 14.44 years, 6868 (1.72%) participants developed glaucoma. Multivariate Cox regression revealed that higher levels of HDL-C were associated with an increased risk of glaucoma (HR for 1-SD increase in HDL-C 1.05, 95% CI 1.02 to 1.08, p=0.001), while elevated levels of LDL-C (HR 0.96, 95% CI 0.94 to 0.99, p=0.005), TC (HR 0.97, 95% CI 0.94 to 1.00, p=0.037) and TG (HR 0.96, 95% CI 0.94 to 0.99, p=0.008) were all associated with reduced risk. The analysis examining the associations between polygenic risk score of serum lipids and glaucoma showed per 1-SD increment of HDL-C genetic risk was associated with a 5% greater hazard of glaucoma (HR 1.05, 95% CI 1.00 to 1.11, p=0.031). However, the polygenic risk score of LDL-C, TC, and TG did not show a significant association with glaucoma.

Conclusions: Elevated HDL-C is associated with an increased risk of glaucoma, while elevated LDL-C, TC, and TG levels are associated with a lower risk of glaucoma. This study enhances our understanding of the association between lipid profile and glaucoma and warrants further investigation of lipid-focused treatments in glaucoma management.

Associations between serum lipids and glaucoma: a cohort study of 400 229 UK Biobank participants - PubMed

Elevated HDL-C is associated with an increased risk of glaucoma, while elevated LDL-C, TC, and TG levels are associated with a lower risk of glaucoma. This study enhances our understanding of the association between lipid profile and glaucoma and warrants further investigation of lipid-focused...

pubmed.ncbi.nlm.nih.gov

 

[aDw32]

Testosterone exacerbates neutrophilia and cardiac injury in myocardial infarction via actions in bone marrow​

Testosterone exacerbates neutrophilia and cardiac injury in myocardial infarction via actions in bone marrow - Nature Communications

Men develop larger myocardial infarction (MI) sizes than women. Here, the authors show that male sex and testosterone, via bone marrow stroma, exacerbates MI-induced neutrophilia and cardiac injury and that response to anti-inflammatory treatment in MI is greater in men than women

www.nature.com

"A new study has discovered the reason why men tend to sustain more heart muscle damage following a heart attack than women: the hormone testosterone. The researchers have also discovered a potential fix in the form of an existing drug."
Background: Testosterone has been implicated in worsening myocardial infarction (MI) injury by promoting neutrophilia, which increases infarct size and cardiac damage. This study explores the role of testosterone in MI outcomes and evaluates potential therapeutic strategies to mitigate its effects.

Methods: Researchers conducted experiments on male and female mice, comparing neutrophil levels and infarct sizes post-MI. Castration was used to induce testosterone deficiency, and its effects were analyzed. In addition, some castrated mice received testosterone replacement to evaluate its impact. Androgen receptor (AR) knockout models were also used to determine the role of testosterone signaling in bone marrow stromal cells (BMSCs). Clinical trial data from patients with first-time MI were analyzed to assess sex differences in neutrophil response and the efficacy of IL-6 receptor inhibitor tocilizumab.

Results: Male mice exhibited significantly higher neutrophil counts and larger infarct sizes than females. Castration reduced neutrophil levels by 91%, leading to smaller infarct sizes and improved survival. Testosterone replacement reversed these benefits, increasing markers of cardiac injury. AR knockout in BMSCs mimicked the protective effects of castration, suggesting that testosterone influences neutrophil release via the suppression of CXCL12. Clinical data showed that men had higher neutrophilia than women post-MI, and tocilizumab was more effective at reducing infarct size in men.

Conclusions: Testosterone contributes to greater cardiac injury in MI by increasing neutrophil mobilization from the bone marrow. Lowering testosterone levels or inhibiting AR activity may provide cardioprotective benefits. These findings highlight the importance of considering sex differences in developing anti-inflammatory treatments for MI. Further research is needed to explore long-term clinical applications and potential therapeutic interventions.

My conclusion? Avoid hart attacks

 

[Stewie]

Testosterone exacerbates neutrophilia and cardiac injury in myocardial infarction via actions in bone marrow​

Testosterone exacerbates neutrophilia and cardiac injury in myocardial infarction via actions in bone marrow - Nature Communications

Men develop larger myocardial infarction (MI) sizes than women. Here, the authors show that male sex and testosterone, via bone marrow stroma, exacerbates MI-induced neutrophilia and cardiac injury and that response to anti-inflammatory treatment in MI is greater in men than women

www.nature.com

"A new study has discovered the reason why men tend to sustain more heart muscle damage following a heart attack than women: the hormone testosterone. The researchers have also discovered a potential fix in the form of an existing drug."
Background: Testosterone has been implicated in worsening myocardial infarction (MI) injury by promoting neutrophilia, which increases infarct size and cardiac damage. This study explores the role of testosterone in MI outcomes and evaluates potential therapeutic strategies to mitigate its effects.

Methods: Researchers conducted experiments on male and female mice, comparing neutrophil levels and infarct sizes post-MI. Castration was used to induce testosterone deficiency, and its effects were analyzed. In addition, some castrated mice received testosterone replacement to evaluate its impact. Androgen receptor (AR) knockout models were also used to determine the role of testosterone signaling in bone marrow stromal cells (BMSCs). Clinical trial data from patients with first-time MI were analyzed to assess sex differences in neutrophil response and the efficacy of IL-6 receptor inhibitor tocilizumab.

Results: Male mice exhibited significantly higher neutrophil counts and larger infarct sizes than females. Castration reduced neutrophil levels by 91%, leading to smaller infarct sizes and improved survival. Testosterone replacement reversed these benefits, increasing markers of cardiac injury. AR knockout in BMSCs mimicked the protective effects of castration, suggesting that testosterone influences neutrophil release via the suppression of CXCL12. Clinical data showed that men had higher neutrophilia than women post-MI, and tocilizumab was more effective at reducing infarct size in men.

Conclusions: Testosterone contributes to greater cardiac injury in MI by increasing neutrophil mobilization from the bone marrow. Lowering testosterone levels or inhibiting AR activity may provide cardioprotective benefits. These findings highlight the importance of considering sex differences in developing anti-inflammatory treatments for MI. Further research is needed to explore long-term clinical applications and potential therapeutic interventions.

My conclusion? Avoid hart attacks

Murine cytokine expression and activation differ vastly compared to humans. Immulogical responses differ between species. I've mentioned this several times in the past extrapolating such models.

This is one of several different, very well defined literatures denoting the difference.

Human neutrophils ≠ murine neutrophils: does it matter? - PMC

Human and murine neutrophils differ with respect to representation in blood, receptors, nuclear morphology, signaling pathways, granule proteins, NADPH oxidase regulation, magnitude of oxidant and hypochlorous acid production, and their repertoire ...

pmc.ncbi.nlm.nih.gov

 

[KingOfSushi]

FDA issues class-wide labeling changes for testosterone products

FDA issues class-wide labeling changes for testosterone products

www.fda.gov

Found this interesting

 

[nothuman]

Not new research, but I asked Grok AI if low HDL is harmful when LDL is less than 100. The answer appears to be not really.


The question of whether low HDL (high-density lipoprotein, or "good cholesterol") is harmful when LDL (low-density lipoprotein, or "bad cholesterol") is below 100 mg/dL is an interesting one, as it challenges the conventional focus on HDL as a protective factor against cardiovascular disease (CVD). Let’s break this down based on available research up to my knowledge base and address what studies say about this specific scenario.

### General Context
- **HDL Role**: HDL is traditionally viewed as cardioprotective because it facilitates reverse cholesterol transport (removing cholesterol from arteries) and has anti-inflammatory properties. Low HDL (<40 mg/dL in men, <50 mg/dL in women) is often considered a risk factor for CVD in guidelines like those from the American Heart Association.
- **LDL Role**: LDL below 100 mg/dL is generally considered "optimal" or "near optimal" per standard lipid guidelines, suggesting a lower risk of atherosclerosis.
- **Interaction**: The interplay between low HDL and low LDL is less straightforward, and research has increasingly questioned whether low HDL is universally harmful, especially when LDL is well-controlled.

### Studies Addressing Low HDL with Low LDL
While no single study perfectly isolates "low HDL with LDL <100" as its primary focus, several investigations provide relevant insights:

1. **Framingham Heart Study (Revisited Data)**:
- The Framingham cohort, a foundational study for lipid-CVD relationships, initially showed low HDL as an independent risk factor for coronary heart disease (CHD), even when total cholesterol was low. However, later analyses (e.g., Gordon et al., 1989, and subsequent reviews) suggested that the risk from low HDL diminishes when LDL is very low. For example, in subgroups with LDL <100 mg/dL, the predictive power of HDL for CHD events weakened significantly, though it wasn’t entirely absent.

2. **Atherosclerosis Risk in Communities (ARIC) Study**:
- This large cohort study (e.g., Sharrett et al., 2001) examined lipid profiles and CVD outcomes. In individuals with LDL <100 mg/dL, low HDL was still associated with a modest increase in risk, but the hazard ratio was much lower compared to when LDL was elevated. This suggests that low HDL’s harm is context-dependent, with LDL acting as a modifier.

3. **Post-Hoc Analyses of Statin Trials**:
- Studies like the **JUPITER trial** (Ridker et al., 2008) evaluated rosuvastatin in patients with low LDL (<130 mg/dL at baseline) and low HDL. In participants achieving LDL <100 mg/dL on treatment, low HDL did not significantly predict major cardiovascular events. This hints that aggressive LDL reduction may mitigate the risk of low HDL.
- Similarly, the **TNT trial** (Barter et al., 2007) found that among patients with LDL <70 mg/dL on atorvastatin, HDL levels had minimal impact on residual CVD risk.

4. **Mendelian Randomization Studies**:
- Genetic studies (e.g., Voight et al., 2012, *Nature Genetics*) used Mendelian randomization to test HDL’s causal role in CVD. They found that genetically low HDL (isolated from LDL levels) did not consistently increase CVD risk when LDL was low. This challenges the idea that low HDL is inherently harmful, suggesting it may be more of a marker than a direct cause when LDL is controlled.

5. **Cardiovascular Health Study (CHS)**:
- In older adults with LDL <100 mg/dL, low HDL was associated with increased CVD risk in some analyses (e.g., Curb et al., 2004), but the effect size was small, and other factors (e.g., triglycerides, inflammation) often confounded the relationship.

### Key Takeaways from Studies
- **Reduced Harm**: When LDL is below 100 mg/dL, the harmful impact of low HDL appears to be diminished. Many studies show that low HDL’s association with CVD weakens significantly in this context, likely because LDL-driven plaque formation (atherogenesis) is less active.
- **Not Entirely Benign**: Some residual risk may persist with low HDL, particularly if other risk factors (e.g., high triglycerides, diabetes, or smoking) are present. However, the absolute risk increase is typically small when LDL is low.
- **Functional HDL Matters**: Emerging research (e.g., Rader & Hovingh, 2014, *The Lancet*) suggests that HDL quality (its functionality in cholesterol efflux) may matter more than its quantity. Low HDL levels might not be harmful if the HDL is still effective, which isn’t always measured in standard studies.

### Limitations
- Most studies don’t specifically stratify for "LDL <100 mg/dL and low HDL" as a primary endpoint, so we’re often interpreting subgroup or post-hoc data.
- Observational studies can’t fully prove causation, and interventional trials raising HDL (e.g., with niacin or CETP inhibitors) have famously failed to reduce CVD risk, even with low LDL, casting doubt on HDL’s role.

### Conclusion
No definitive study says low HDL is *completely harmless* when LDL is <100 mg/dL, but the evidence strongly suggests its harm is substantially reduced. The consensus leans toward LDL as the dominant driver of CVD risk, with low HDL playing a secondary role that’s less impactful in a low-LDL environment.

 

[aDw32]

Not scientific publication yet, but super interesting.

There’s a chance we’ll still be lifting easily into our 100s

"Scientists Have Created A Hydrogel That Strengthens Bones In Weeks. Bone Density Increased By 5X In A Lab"

Scientists Have Created A Hydrogel That Strengthens Bones In Weeks. Bone Density Increased By 5X In A Lab - Gulf Insider

A groundbreaking injectable hydrogel may soon offer a faster, more effective treatment for osteoporosis a condition that weakens bones & increases fracture risk

www.gulf-insider.com

 

[Swifto]

Vitamin E lowers LDL.



Nutr Metab Cardiovasc Dis

2025 Feb 25:103964.
doi: 10.1016/j.numecd.2025.103964.Online ahead of print.

Vitamin E ameliorates blood cholesterol level and alters gut microbiota composition: A randomized controlled trial​

Bangwei Chen 1, Yaxin Li 2, Zhiming Li 3, Xiaojie Hu 4, Hefu Zhen 3, Hongyun Chen 3, Chao Nie 3, Yong Hou 3, Shida Zhu 5, Liang Xiao 3, Tao Li 6
Affiliations expand

• PMID: 40087044
• DOI: 10.1016/j.numecd.2025.103964

Abstract​

Background and aims: Antioxidants, including vitamin E (VE) and grape seed extract (GSE), as anti-aging supplementation have been widely used to improve human health. The gut microbiota plays a crucial role in health and affects the treatment effect of various interventions. However, the role of gut microbiota in VE remains unclear. This study aimed to assess the longitudinal impact of VE treatment on body health and the gut microbiota.
Methods and results: A randomized controlled trial was conducted with 90 healthy individuals. The participants were randomly assigned to three groups: a treatment group receiving VE, another antioxidant treatment group receiving GSE, and a control group receiving a placebo. We found that VE ameliorated blood cholesterol levels by reducing the levels of low-density lipoprotein cholesterol (LDL-C) in healthy volunteers. After the intervention, there was an increase in the relative abundance of short-chain fatty acid (SCFA)-producing bacteria and bile acid metabolizers. Specifically, the abundances of Lachnospira sp. and Faecalibacterium spp. increased in the VE. Interestingly, the gut microbiota of poor responders harbored a greater proportion of disease-associated bacterial species.
Conclusions: VE could promote health by lowering LDL-C, partly and indirectly by affecting gut bacteria with the ability to produce SCFAs or metabolize bile acids.

Source: https://pubmed.ncbi.nlm.nih.gov/40087044/

 

[Swifto]

Nutrition
2025 Feb 18:134:112717.
doi: 10.1016/j.nut.2025.112717. Online ahead of print.

Ellagic acid ameliorates atherosclerosis by inhibiting PCSK9 through the modulation of FoxO3 and HNF1α​

Li-Tian Wang 1, Huai-Liu Yin 2, Ya-Min Jin 2, Dan-Dan Hu 3, Xiang-Xuan Yang 2, Jun Sheng 4, Ye-Wei Huang 5, Xuan-Jun Wang 6
Affiliations expand

• PMID: 40086009
• DOI: 10.1016/j.nut.2025.112717

Abstract​

Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) hinders the clearance of low-density lipoprotein cholesterol (LDL-C) by promoting the degradation of the low-density lipoprotein receptor (LDLR), leading to the accumulation of LDL-C and thus becoming an important cause of atherosclerosis. Ellagic acid, a naturally occurring polyphenol widely present in fruits, vegetables, and nuts, has attracted significant attention due to its potential role in the prevention and treatment of cardiovascular diseases. However, the molecular mechanisms by which ellagic acid alleviates atherosclerosis by inhibiting PCSK9 are not fully understood.
Materials and methods: This study further validated the mechanism of action of ellagic acid through in vitro HepG2 cell experiments and a high-fat diet-induced ApoE-/- mouse model.
Results: The results showed that ellagic acid significantly reduced the expression and secretion of PCSK9 while upregulating LDLR protein levels; its mechanism is related to the inhibition of hepatocyte nuclear factor 1α (HNF1α) expression and the promotion of forkhead box O3 (FoxO3) expression increase. Additionally, ellagic acid reduced aortic plaque deposition in mice induced by a high-fat diet; consistent with the in vitro experimental results, ellagic acid lowered the expression and secretion of PCSK9 and elevated LDLR protein levels by inhibiting HNF1α and increased FoxO3 expression.
Conclusions: In summary, this study demonstrates that ellagic acid inhibits PCSK9 by regulating HNF1α and FoxO3, thereby increasing LDLR levels and alleviating atherosclerosis. This finding not only consolidates the scientific basis of plant-based diets for preventing cardiovascular diseases but also provides an important direction for developing functional foods and nutritional intervention strategies based on natural polyphenols.
Keywords: Atherosclerosis; Ellagic acid; LDL-C; LDLR; PCSK9.

Source: https://pubmed.ncbi.nlm.nih.gov/40086009/

 

[Swifto]

Lipids Health Dis

2025 Mar 13;24(1):92.
doi: 10.1186/s12944-025-02502-z.

Causal relationship between drug target genes of LDL-cholesterol and coronary artery disease: drug target Mendelian randomization study​

Yongho Jee 1, Jong Won Shin 2, Mikyung Ryu 3, Tae-Jin Song 4
Affiliations expand

• PMID: 40082904
• DOI: 10.1186/s12944-025-02502-z

Abstract​

Background: High LDL-cholesterol (LDL-C) is a well-known risk factor for coronary artery disease (CAD). PCSK9, HMGCR, NPC1L1, ACLY, and LDLR gene have been reported as lipid lowering drug genes related to LDL-C lowering. However relevant Asian studies were rare.
Methods: We examined the causality between LDL-c drug target genes and CAD using Korean and Japanese data using the two sample Mendelian Randomization (MR) method. We conducted two-sample MR analysis of LDL-c lowering drug target genes (7 Single-nucleotide polymorphisms (SNP) in PCSK9, 6 SNPs in HMGCR, 5 SNPs in NPC1L1, 9 SNPs in ACLY, 3 SNPs in LDLR) and CAD. We used summary statistics data from the Korean Genome Epidemiology Study (KOGES) for LDL-C data, and Biobank of Japan (BBJ) for CAD data.
Results: For every 10 mg/dl decrease in LDL-C determined by four significant SNPs in the PCSK9 gene, the risk of CAD decreased by approximately 20% (OR = 0.80, 95% CI: 0.75-0.86). The risk of CAD decreased by 10% for every 10 mg/dl decrease in LDL-C due to the six significant SNPs in the HMGCR gene (OR = 0.90, 95% CI: 0.86-0.94). Due to the two significant SNPs in the gene LDLR, the risk of CAD decreased by approximately 26% for every 10 mg/dl decrease in LDL-C (OR = 0.74, 95% CI: 0.66-0.82). The combined effect on CAD showed the largest effect size for the PCSK9 gene and LDLR gene, and the reduced CAD risk induced by these two genes together was OR = 0.78 (95%CI, 0.74-0.83). Finally, the combined effect of all three genes (PCSK9, HMGCR, and LDLR) was OR = 0.85 (95%CI, 0.79-0.91).
Conclusion: LDL-C reduction estimated by SNPs in LDL-C lowering drug target genes significantly reduced the risk of CAD. We found the potential of using of proxy research design for clinical trials using LDL-C lowering drugs.

Source: https://pubmed.ncbi.nlm.nih.gov/40082904/

 

[Swifto]

​

Title & authors Abstract
Arch Physiol Biochem

. 2025 Mar 14:1-15.
doi: 10.1080/13813455.2025.2476644.Online ahead of print.

Anti-atherogenic properties of Plectranthus glandulosus Hook. F. (Lamiaceae) leaves through lipid profile regulation, oxidative stress reduction, and aorta media thickening attenuation in high-fat diet-fed Sprague-Dawley rats​

Djamila Zouheira 1, Anu Kajal 2, Moïse Legentil Nchouwet 3, Sylviane Laure Poualeu Kamani 3, Lauve Rachel Tchokouaha Yamthe 1, Gabriel Agbor Agbor 1, Sylvie Lea Wansi Ngnokam 3, Randhir Singh 4
Affiliations expand

• PMID: 40084602
• DOI: 10.1080/13813455.2025.2476644

Abstract​

This study investigated the anti-atherogenic effects of Plectranthus glandulosus leaves aqueous, hydro-ethanolic extracts, and ethyl acetate fraction at doses of 100, 200, and 400 mg/kg for 21 d. As results, at the dose of 400 mg/kg, the ethyl acetate fraction significantly (p < .001) decreased the level of total cholesterol (112.52 ± 1.21 mg/dL), triglyceride (76.47 ± 0.97 mg/dL), and LDL-C (22.01 ± 2.92 mg/dL). Whereas, a significant (p < .001) increase was observed in the level of HDL-C (74.97 ± 1.99 mg/dL). Moreover, the atherogenic index significantly (p < .001) decreased (0.008 ± 0.00 mg/dL), while the percentage of atherogenic protection increased (99.13 ± 0.78%). The activity of antioxidant enzymes increased significantly (p < .001), while malondialdehyde concentration decreased. The thickening of aorta media (67.27 ± 7.15 µm) was also attenuated significantly (p < .001). Thus, our finding supports the use of Plectranthus glandulosus for future
atherosclerosis drug discovery.

Source: https://pubmed.ncbi.nlm.nih.gov/40084602/

 

[Swifto]

Please let me know how this goes. Interested in equipoise and lipids for sure.

I will say Primo hits E2 but EQ is a hammer did my E2.

My bloods were very very good.

Estrogen was 89 pmol/L.

No AI.

I think my worse lipid bloods on Primo are more attributed to AI overuse and not Primo per se. So now I'm cutting on Test 350 and Primo 350 and will get blood done in 6-7 weeks time.

All my lipids were in range comfortably bar HDL which was 28. Apo B was 0.91.

Test/EQ for mass going forward, keeping doses low and HGH 3.6iu Geno.

 

[Stewie]

Please let me know how this goes. Interested in equipoise and lipids for sure.

I will say Primo hits E2 but EQ is a hammer did my E2.

Take this at face value. May or may extrapolate to us homo sapiens.

Frontiers | Boldenone Undecylenate-Mediated Hepatorenal Impairment by Oxidative Damage and Dysregulation of Heat Shock Protein 90 and Androgen Receptors Expressions: Vitamin C Preventive Role

Boldenone Undecylenate (BLD) is a synthetic derivative of testosterone and a widely used anabolic androgenic steroid. The health risk of BLD use as a pharmac...

www.frontiersin.org

 

[Mufasa123]

Take this at face value. May or may extrapolate to us homo sapiens.

Frontiers | Boldenone Undecylenate-Mediated Hepatorenal Impairment by Oxidative Damage and Dysregulation of Heat Shock Protein 90 and Androgen Receptors Expressions: Vitamin C Preventive Role

Boldenone Undecylenate (BLD) is a synthetic derivative of testosterone and a widely used anabolic androgenic steroid. The health risk of BLD use as a pharmac...

www.frontiersin.org

Thanks for this. Seems like it hits a lot in the study though few report seeing all of these impacts on their own bloods. I'll just have to try and test impacts.

Ultimate goal is to find a well tolerated compound that can be run long(er) term without impairment. Test and nandrolone have met this for me and just trying to find another.

Test/deca at 200/200 is my main cruise dose. Zero impacts on bloods from baseline. I've run 2+ years straight and countless cruises (current is 30+ weeks) over ~15 years. Blast doses up to 750/600 don't move anything either - maybe higher but I don't have bloods for it. For the body, in addition to enhanced anabolic effects I feel good and almost seems protective of wear/tear on my joints. Slightly decreased sex drive maybe but non issue for me (others mileage and negative risk assessment may vary but this exercise is just for me and n=1).

I tried primo but it hits HDL significantly at blast doses and lots of people report similarly. Lowers E2 but not uncontrollably. End of the day, it's a shorter cruise compound for me and valid for blasts though probably as a 3rd compound in stack as it's weak and I tolerate stronger drugs fine with some movement but nothing major in bloods.

Masteron might work fine. Hits some people's lipids but I can't find a significant effect and regardless much less than primo. Only negative is anabolic effect, at least for me, is super weak. Basically injectable Proviron. Might work out.

Equipoise is one I've oddly not used much - and my ped use goes back into early 1990s. One thing I have found on a trial blast run is that it is the grim reaper of my E2. 750 test, 600 deca and 600 equipoise and E2 was near zeroed. I needed test at 1000 to get E2 to low 20s. That said maybe there's a ratio that could work for a cruise and I'd mess with it some if EQ hits nothing else I bloods significantly. Might run during upcoming blast.