NAC Benefits: HDL and More

[Nelson Vergel]

NAC does not cause rash or flushing as Niacin. Men on high doses of testosterone have low HDL.

Pharmacol Res. 1993 Oct-Nov;28(3):213-8.
Dose-related increase of HDL-cholesterol levels after N-acetylcysteine in man.
Franceschini G, Werba JP, Safa O, Gikalov I, Sirtori CR.
Source
Centre E. Grossi Paoletti, University of Milano, Italy.
Abstract

Changes in plasma lipid-lipoprotein levels were evaluated in 10 hyperlipidemic patients during treatment with progressive doses (from 1200 mg day-1 to 3600 mg day-1) of N-acetylcysteine (NAC). Plasma total cholesterol and triglyceride levels, as well as those of lipoprotein (a) did not change to an appreciable extent, even with the highest dosage. However, the HDL-cholesterol levels showed a significant, dose-related rise, the mean absolute increase, with the highest NAC dose, being of approximately 10 mg dl-1 (16.2%). The rise of HDL-cholesterol was independent of changes in other lipid-lipoprotein parameters, suggesting a possible direct effect of NAC on the HDL system.

http://www.amazon.com/Jarrow-Formula…2&keywords=nac


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[Vince]

NAC does not cause rash or flushing as Niacin. Men on high doses of testosterone have low HDL.

Pharmacol Res. 1993 Oct-Nov;28(3):213-8.
Dose-related increase of HDL-cholesterol levels after N-acetylcysteine in man.
Franceschini G, Werba JP, Safa O, Gikalov I, Sirtori CR.
Source
Centre E. Grossi Paoletti, University of Milano, Italy.
Abstract

Changes in plasma lipid-lipoprotein levels were evaluated in 10 hyperlipidemic patients during treatment with progressive doses (from 1200 mg day-1 to 3600 mg day-1) of N-acetylcysteine (NAC). Plasma total cholesterol and triglyceride levels, as well as those of lipoprotein (a) did not change to an appreciable extent, even with the highest dosage. However, the HDL-cholesterol levels showed a significant, dose-related rise, the mean absolute increase, with the highest NAC dose, being of approximately 10 mg dl-1 (16.2%). The rise of HDL-cholesterol was independent of changes in other lipid-lipoprotein parameters, suggesting a possible direct effect of NAC on the HDL system.

http://www.amazon.com/Jarrow-Formula…2&keywords=nac


The post NAC Benefits: HDL and More appeared first on Testosterone Wisdom.

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Based on the study published in Parkinsonism & Related Disorders (2026), titled "N-Acetylcysteine is associated with changes in functional connectivity in patients with Parkinson's disease," here is a summary focusing on the specific improvements observed after treatment.

Overview of the Study

The research evaluated 44 patients with Parkinson's Disease (PD) randomized into two groups:

NAC Group: Received weekly intravenous infusions (50 mg/kg) plus daily oral doses (500 mg x2) for six months, alongside standard care.

Control Group: Received standard care only.

Key Functional Connectivity (FC) Improvements

The most significant findings involved the "wiring" or communication between the basal ganglia (the brain's motor control center) and other cortical regions. After six months of NAC treatment, the following changes were observed:

Restoration of Motor Network Connectivity: NAC patients showed significantly different functional connectivity between the basal ganglia and key motor-related areas, specifically the:

Rolandic Operculum: A region vital for sensory-motor integration.

Precentral and Postcentral Gyri: Areas responsible for executing motor commands and processing touch/position.

Precuneus Integration: There was a notable change in connectivity with the precuneus, a hub of the Default Mode Network (DMN). This is significant because the precuneus is involved in self-awareness and visuospatial processing, which are often impaired in PD.

Clinical & Symptomatic Improvements

The imaging changes were not just "on paper"; they correlated directly with how patients felt and moved:

Improved UPDRS Scores: Patients in the NAC group showed a significant improvement (reduction) in their Unified Parkinson’s Disease Rating Scale (UPDRS) scores compared to the control group.

Brain-Behavior Correlation: Specifically, the changes in connectivity within the precuneus were directly correlated with the improvements in clinical symptoms. This suggests that the NAC treatment helped "re-sync" brain regions that had become disconnected due to the disease.

Dopaminergic Support: Building on previous work by the same team, these connectivity changes likely reflect NAC’s ability to increase Glutathione (GSH) levels and support Dopamine Transporter (DAT) binding, essentially protecting the surviving dopamine neurons from oxidative stress.

https://www.prd-journal.com/article/S1353-8020(26)00042-8/fulltext

Conclusion



The study concludes that NAC is a promising disease-modifying intervention. Unlike treatments that only mask symptoms (like Levodopa), NAC appears to alter the underlying functional architecture of the brain, leading to measurable improvements in motor and potentially cognitive stability through its antioxidant properties.

​

​

 

[Fernando Almaguer]

NAC does not cause rash or flushing as Niacin. Men on high doses of testosterone have low HDL.

Pharmacol Res. 1993 Oct-Nov;28(3):213-8.
Dose-related increase of HDL-cholesterol levels after N-acetylcysteine in man.
Franceschini G, Werba JP, Safa O, Gikalov I, Sirtori CR.
Source
Centre E. Grossi Paoletti, University of Milano, Italy.
Abstract

Changes in plasma lipid-lipoprotein levels were evaluated in 10 hyperlipidemic patients during treatment with progressive doses (from 1200 mg day-1 to 3600 mg day-1) of N-acetylcysteine (NAC). Plasma total cholesterol and triglyceride levels, as well as those of lipoprotein (a) did not change to an appreciable extent, even with the highest dosage. However, the HDL-cholesterol levels showed a significant, dose-related rise, the mean absolute increase, with the highest NAC dose, being of approximately 10 mg dl-1 (16.2%). The rise of HDL-cholesterol was independent of changes in other lipid-lipoprotein parameters, suggesting a possible direct effect of NAC on the HDL system.

http://www.amazon.com/Jarrow-Formula…2&keywords=nac


The post NAC Benefits: HDL and More appeared first on Testosterone Wisdom.

Continue reading...

NAC may be more helpful in resoring glutathione in older adults. 45 and older perhaps. Younger bucks don't need the increase in antioxidants as much

 

[Vince]

NAC may be more helpful in resoring glutathione in older adults. 45 and older perhaps. Younger bucks don't need the increase in antioxidants as much

Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Benefits both Health Span and Lifespan | USC Longevity Institute

Discover how GlyNAC supplementation can combat hallmarks of aging. This double-blind randomized clinical trial reveals GlyNAC's potential to correct glutathione deficiency, reduce oxidative stress and improve mitochondrial function and physical health in older adults, addressing key hallmarks of...

gero.usc.edu

 

[Fernando Almaguer]

Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Benefits both Health Span and Lifespan | USC Longevity Institute

Discover how GlyNAC supplementation can combat hallmarks of aging. This double-blind randomized clinical trial reveals GlyNAC's potential to correct glutathione deficiency, reduce oxidative stress and improve mitochondrial function and physical health in older adults, addressing key hallmarks of...

gero.usc.edu

I wonder how old they suggest is good to take.

 

[Nelson Vergel]

" These supplements are filled into capsules by a pharmacist, and provided monthly to study participants at doses of 100 mg/kg/d each of glycine and NAC, and 200 mg/kg/d of alanine. " Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial - PMC

That is 8,300 mg/day for a 83 Kg man of Glycine and NAC (each). That would probably be total of 18 capsules per day (9 twice per day). Wow!

I have been taking 1200 mg/day (1 tablet twice per day) of NAC for 20 years.

 

[Nelson Vergel]

Comprehensive Analysis of N-Acetylcysteine (NAC) and Supplementation for Male Health​

Executive Summary​

N-Acetylcysteine (NAC) is a cysteine-derived amino acid compound that serves as a potent antioxidant by facilitating the production of intracellular glutathione (GSH), often referred to as the "mother of all detoxifiers." Synthesized from clinical data and expert forum discussions, this document outlines the multifaceted benefits of NAC, particularly for men undergoing testosterone replacement therapy (TRT) or facing fertility challenges.
Critical Takeaways:

• Liver Protection: NAC is the standard of care for acetaminophen overdose and is highly effective at normalizing elevated liver enzymes (AST/ALT).
• Lipid Management: Clinical studies demonstrate a dose-related increase in HDL-cholesterol (up to 16.2%), which is crucial for men on high doses of testosterone that typically suppress "good" cholesterol.
• Reproductive Health: NAC improves spermatogenesis, testicular tissue health, and sperm motility by countering oxidative stress and environmental pollutants.
• Metabolic Synergy: High-dose combinations of Glycine and NAC (GlyNAC) have shown promise in reversing insulin resistance and improving mitochondrial function in Type 2 Diabetes patients.
• Safety Profile: While concerns regarding pulmonary arterial hypertension (PAH) and elevated hematocrit exist in animal models or anecdotal reports, human therapeutic doses (600–1200 mg/day) are generally considered safe and do not appear to deplete essential trace minerals like zinc or copper.

1. N-Acetylcysteine (NAC): Mechanism and Clinical Utility​

NAC has been utilized for over 60 years, primarily as a mucolytic agent to clear airways by breaking molecular bonds in mucus (mucin proteins). It is included on the World Health Organization’s list of essential medicines.

1.1 Mechanism of Action​

• Glutathione Precursor: NAC provides the unadulterated cysteine required for the body to synthesize glutathione. It targets multiple pathways, including glutamatergic transmission, neurotrophins, apoptosis, and inflammatory pathways.
• Antioxidant Power: By increasing glutathione, NAC medicates oxidative stress-induced disorders in the cardiovascular, renal, hepatic, and reproductive systems.

1.2 Clinical Applications​

• Acute Toxicity: Oral administration for acetaminophen (Tylenol) overdose.
• Respiratory Health: Used as an inhalant or oral solution to treat COPD, chronic bronchitis, and cystic fibrosis.
• Neuropsychiatry: Emerging evidence suggests utility in treating addictions (cocaine, cannabis, smoking), Alzheimer’s, Parkinson’s, autism, schizophrenia, and depression.
• Thrombolytic Potential: Recent mouse studies suggest IV NAC may unblock arteries by breaking down Von Willebrand factor bonds in blood clots, offering a potential future strategy for stroke and myocardial infarction management.

2. Impact on Male Reproductive Health​

NAC is identified as a capable tool for addressing male infertility, particularly in environments with high pollution.

2.1 Spermatogenesis and Testicular Function​

A systematic review of scientific articles (1994–2020) confirmed that NAC:

• Improves and normalizes spermatogenesis.
• Protects testicular tissue and improves biochemical parameters.
• Boosts the reproductive system's defense against oxidative stress.
• Increases sperm motility (often used in conjunction with Coenzyme Q10).

2.2 Prescriptive Recommendations​

Experts recommend NAC as an adjunctive therapy for diseases caused by oxidative stress induction in the male reproductive system to enhance fertility health.

3. Cardiovascular and Lipid Management​

For men on TRT, lipid profile shifts—specifically the lowering of HDL—are a common concern. NAC provides a non-flushing alternative to Niacin for lipid management.

3.1 HDL Enhancement​

A study published in Pharmacological Research involving hyperlipidemic patients showed:

• Dose-Related Rise: HDL-cholesterol increased significantly with progressive doses (1200 mg to 3600 mg/day).
• Mean Increase: The highest dose resulted in an absolute increase of approximately 10 mg/dl (a 16.2% rise).
• Independence: The rise in HDL was independent of changes in other lipid parameters, suggesting a direct effect on the HDL system.

3.2 Plaque and Blood Pressure​

While some users report blood pressure spikes when starting NAC, others use it specifically to stop the oxidation of LDL particles and potentially dissolve plaque (based on IV animal models).

4. Liver Detoxification Protocol​

Elevated liver enzymes (AST/ALT) can indicate hepatotoxicity or fatty liver disease. NAC is a cornerstone of liver health due to its ability to boost glutathione within the liver.

4.1 Recommended Liver Detox Regimen​

The following protocol is suggested for 30–90 days to address elevated enzymes:

Compound	Dosage	Frequency
Silymarin (Milk Thistle)	200 mg	3 capsules daily
N-Acetylcysteine (NAC)	600 mg	1 capsule twice daily
B-Complex 100	100 mg	1 capsule daily
L-Glutathione (Injectable)	200 mg/ml	1 ml daily (Sub-Q)

4.2 Hormonal Balance​

A healthy liver is critical for processing and directing sex hormones. Liver disease (such as fatty liver) has been shown to decrease Sex Hormone Binding Globulin (SHBG), though not necessarily testosterone. Maintaining liver health via NAC helps balance testosterone, estradiol, DHT, and SHBG.

5. Metabolic Health and Insulin Resistance​

Recent research into "GlyNAC" (the combination of Glycine and NAC) suggests significant benefits for mitochondrial health.

• Insulin Sensitivity: High doses of Glycine (100mg/kg) and NAC (100mg/kg) used over two weeks improved mitochondrial fuel oxidation and lowered insulin resistance in Type 2 Diabetes patients.
• Dosage Context: For a 70kg (154lb) human, this translates to approximately 7g of Glycine and 7g of NAC per day.

6. Safety, Dosage, and Interaction Concerns​

6.1 Mineral Depletion​

There is a common concern that NAC, as a chelating agent, may deplete trace minerals. However, a study in the European Journal of Clinical Pharmacology found that oral doses of 600 mg/day for two weeks caused no significant change in the plasma concentration or urinary excretion of calcium, magnesium, iron, zinc, or copper.

6.2 The Hematocrit Question​

Some evidence suggests NAC may increase red blood cell count or elevate hematocrit (HCT) by stimulating erythropoietin (EPO) production. This is of particular relevance to TRT patients who already struggle with high HCT. While some users report a several-point bump in HCT, others find their levels remain correlated only to their testosterone status.

6.3 Potential Risks and Controversies​

• Pulmonary Arterial Hypertension (PAH): Research at the University of Virginia suggested NAC could form nitrosothiols that mimic hypoxia, leading to PAH. However, forum experts note these studies used mice and doses 40 times higher than typical human supplementation.
• Pro-oxidant State: Overdosing on antioxidants like NAC can potentially create a pro-oxidant state, especially if reducing agents are depleted.
• Mucus Barriers: As a potent mucolytic, long-term high-dose use might affect necessary mucus barriers in the body.

6.4 Recommended Dosage Schedules​

• Standard Health/Liver Support: 600 mg to 1200 mg per day.
• Timing: Often taken on an empty stomach in the morning, though some prefer taking it with meals to avoid gastrointestinal side effects.
• Product Types: "NAC Sustain" (e.g., Jarrow Formulas) uses a bilayer format (1/3 quick release, 2/3 sustained release) to maintain blood levels beyond the typical 1.5-hour half-life.

7. Comparative Supplement Reference for Men's Health​

Beyond NAC, the source context identifies several key supplements for optimizing male physiology:

Supplement	Purpose	Typical Dose (per Source)
Coenzyme Q10	Cardiovascular health, sperm motility, energy	200 mg–800 mg (take with fat)
Zinc Balance	Testosterone support, DHT/Estradiol modulator	15 mg Zinc / 1 mg Copper
L-Carnitine	Energy, focus, fat metabolism	1000 mg (Breakfast/Lunch)
Vitamin D3	Bone density, metabolic processes	2000 IU–10,000 IU
Creatine	Muscle strength, intracellular water	5 g–10 g (Pre-workout)
SAMe	Fatigue, depression, liver protection	400 mg (Empty stomach)

"Nothing detoxifies the liver better than NAC! It even helps increase HDL that is lowered by higher doses of testosterone." — Nelson Vergel, Founder, ExcelMale.com