Nothing before the 80s AFAIK, but consistent decline since then.
Well, I don’t feel so bad about my free testosterone anymore.
Brian Johnson free testosterone - 8.8
Siim Land - 13.8
Mine at 7.7 is not bad.
However, their total testosterone is about 50% higher than mine.
Actually, after looking at both of their biomarkers, I think only the HSCRP and ALT are out of whack. AST and ALP are fine for me though.
It’s a real head scratcher. I’m guessing there’s a supplement or two that doesn’t agree with my liver and is causing inflammation. Any ideas what could do that?
What’s bicarbonate and Anion gap on CBC?
Does that account for changes in methods of measuring levels of testosterone ?
I am going to add 1 g of Carnosine mixed in my EVOO shot to see if this will reduce my HS-CRP or ALT scores. Any thoughts on this?
Here is what ChatGPT5.0 has to say:
I looked through the clinical and preclinical literature—here’s what I found on whether carnosine (or related histidine-dipeptides) lowers high-sensitivity CRP (hs-CRP) or CRP in humans, plus gaps and what to interpret with caution.
What the studies show & do not show
| Study / Context | Supplement / Dose / Duration | Population | CRP or hs-CRP Findings |
|---|---|---|---|
| Saadati et al., 2024(“Carnosine Supplementation Has No Effect on Inflammatory Markers …”) PubMed+1 | 2 g/day carnosine vs placebo for 14 weeks | Adults with prediabetes or well-controlled type 2 diabetes (diet and/or metformin) | No significant change in CRP (or other measured inflammatory markers) between supplement vs placebo. PubMed+1 |
| de Courten et al., 2016(“Effects of carnosine supplementation on glucose …”) Wiley Online Library+1 | 2 g/day, 12 weeks, pilot RCT | Overweight or obese non-diabetic adults | No change in pro- & anti-inflammatory biomarkers, including plasma hsCRP. Wiley Online Library+2PMC+2 |
| Baye et al., 2018(“Carnosine Supplementation Improves Serum Resistin …”) PMC | Carnosine supplementation (dose unspecified in table; but double-blind placebo control) | Overweight or obese, non-diabetic adults | Reduced resistin & leptin, but no effect on hsCRP in that study. PMC |
| Meta-analysis / Review(Saadati et al., 2024) “Effects of carnosine/HCDs on inflammation markers” Oxford Academic+1 | Aggregated RCTs (mixed dipeptides, sometimes carnosine alone; varying doses/durations) | Various human populations and some children | The pooled analysis suggests some reduction in CRP when combining several studies, but the evidence is low certainty, heterogeneous, and many studies do not isolate carnosine alone. Oxford Academic+2PMC+2 |
Interpretation
From what is currently available in humans:
- No strong or consistent evidence that carnosine supplementation lowers hs-CRP or CRP in populations like overweight/obese non-diabetics, or people with prediabetes / well-controlled T2D, at doses ~1-2 g/day over periods of ~12-14 weeks.
- Some meta-analysis / reviews hint at modest reductions in CRP when considering a mix of studies (some using carnosine, some related compounds), but the certainty is low, and often CRP isn’t a primary outcome or the sample size is modest. Heterogeneity (in population, baseline inflammation, dose, supplement type, length) is large. Oxford Academic+1
- In specific studies, adipokines like leptin or resistin were reduced, but these don’t necessarily correlate to CRP changes in all populations. In the Baye et al. study, despite changes in resistin/leptin, hsCRP didn’t change. PMC
Possible reasons for null / weak effects
Here are several plausible explanations why carnosine might not significantly lower CRP in many human trials:
-
Baseline inflammation low or moderate.
If subjects begin with relatively low CRP/hs-CRP, there’s less room for improvement. -
Population / disease state matters.
In individuals with more severe or uncontrolled inflammation (e.g. poorly controlled diabetes, obesity with high systemic inflammation), the effect might be greater—but such studies are rare. -
Dose / duration insufficient.
Many trials use ~1-2 g/day for 8-14 weeks. It could be that higher doses or longer supplementation are needed to see changes in CRP under some conditions. -
Supplement form & bioavailability.
Carnosine is subject to degradation; levels in human plasma may not be high or sustained enough. Also, variability among individuals in absorption/metabolism might influence effect. -
Measurement issues.
Some studies use total CRP rather than hs-CRP; some are not powered primarily to detect changes in inflammatory biomarkers → risk of type II error (failing to detect existing effect). -
Co-therapy / medications.
In trials with people already on drugs (e.g., metformin) or lifestyle interventions, added effect of carnosine might be small compared to what those baseline therapies already provide.
Bottom line
- As of now, there is no robust human clinical evidence that carnosine reliably lowers hs-CRP or CRP in the typical metabolic or prediabetic populations studied.
- Some signals in mixed meta-analyses are promising, but most RCTs specifically measuring CRP as outcome have not shown significant effects.
- More research is needed, especially in populations with higher baseline inflammation, using higher doses / longer durations, or perhaps carnosinase-resistant analogs.
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@RapAdmin Thanks for that. I had asked Gemini which supplements could reduce HS-CRP and it had said carnosine. I guess I should have done a deeper dive into it. I’ll be using more detailed prompts in the future! 
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Related:
What compounds, supplements or drugs are linked to significant decreases in inflammation markers like CRP in humans?
Response:
Here’s a practical, evidence-first roundup of compounds / drugs / interventions that lower CRP or hs-CRP in humans, with typical direction and magnitude where data are solid.
Cardiometabolic drugs (strongest human evidence)
Statins (e.g., rosuvastatin) – robust hs-CRP lowering independent of LDL
• In JUPITER, rosuvastatin cut hs-CRP ~37% vs placebo alongside 44% event reduction. (New England Journal of Medicine)
IL-1β inhibition (canakinumab) – powerful CRP suppression without lipid effects
• In CANTOS, targeting IL-1β markedly lowered hs-CRP (≈30–40%+) and reduced CV events despite no LDL change. (Dose-response across 50–300 mg). (New England Journal of Medicine)
IL-6 pathway inhibition (tocilizumab; investigational ziltivekimab)
• Tocilizumab rapidly drops CRP (often to very low levels) in inflammatory disease and acute settings. (PMC)
• Ziltivekimab (IL-6 ligand mAb; phase 2) produced large hs-CRP reductions in CKD with elevated hs-CRP (RESCUE/RESCUE-2). (ScienceDirect)
Colchicine (low-dose) – modest hs-CRP lowering, outcome benefits post-MI/chronic CAD
• Pooled patient-level data after MI show lower hs-CRP with colchicine vs control; also cuts recurrent events (COLCOT/LoDoCo programs). (PubMed)
GLP-1 receptor agonists (e.g., semaglutide) – consistent hs-CRP falls (partly weight-mediated)
• Across SUSTAIN/STEP analyses, semaglutide significantly reduced hs-CRP vs comparators; confirmed in STEP 1/3. (PMC)
SGLT2 inhibitors – small but significant CRP reductions
• Meta-analyses show CRP decreases vs placebo (effect size modest and heterogeneous). (Frontiers)
Pure EPA (Icosapent ethyl, 4 g/day) – clinically meaningful hs-CRP drops
• In MARINE/ANCHOR, hs-CRP fell ~20–40% overall; in statin-treated subsets, placebo-adjusted reductions up to ~68% were reported. (Liebert Publishing)
Methotrexate (low-dose) – notable exception
• In CIRT, did not reduce hs-CRP/IL-1β/IL-6 or CV events vs placebo. (New England Journal of Medicine)
Lifestyle & procedures (high signal in humans)
Weight loss (dietary programs) – CRP tracks with fat loss
• Intensive lifestyle intervention cut median hs-CRP ~44% at 1 year (Look AHEAD ancillary). Multiple RCTs show ~25–45% reductions proportional to weight loss. (PMC)
Bariatric/metabolic surgery – large and durable decreases
• hs-CRP typically drops substantially within months and remains lower long-term; effects scale with weight loss. (PMC)
Mediterranean-style dietary patterns – modest reductions
• PREDIMED analyses/reporting show lower CRP/IL-6 with MedDiet adherence (signal clearer for IL-6; CRP effects modest but present in several cohorts). (PMC)
Inflammatory-disease–directed biologics (context-specific)
These can dramatically suppress CRP but are used for defined conditions (RA, vasculitis, cytokine-storm syndromes), not for general risk reduction:
• Tocilizumab (IL-6R mAb) – sharp CRP falls in RA/COVID. (PMC)
• Anakinra (IL-1RA) – hs-CRP reductions seen in dialysis and ACS pilots (magnitude ~~40% in one 24-week dialysis RCT; small n and mixed significance). (PMC)
Quick chooser (what actually moves hs-CRP)
- Biggest, consistent reductions: Statins, IL-1β/IL-6 inhibitors, substantial weight loss (lifestyle or bariatric surgery), EPA (icosapent ethyl), GLP-1 RAs. (New England Journal of Medicine)
- Modest reductions: SGLT2 inhibitors, Mediterranean-style diets. (Frontiers)
- Not effective for hs-CRP: Low-dose methotrexate (CIRT). (New England Journal of Medicine)
Notes
- Magnitudes vary with baseline hs-CRP (higher baseline → larger absolute drops), dose, and population.
- Anti-cytokine biologics are not general-use anti-inflammatories; risks/costs limit them to specific indications.
- For cardiometabolic risk, many clinicians prioritize statins ± EPA, and weight-loss strategies (GLP-1 RA, lifestyle, surgery) because they lower hs-CRP and improve outcomes. (New England Journal of Medicine)
If you want, I can build a one-page table with typical hs-CRP deltas, trial names, doses, and who benefits most to use as a quick reference.
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Ibuprofen can negatively affect the gut microbiome, especially with frequent or long-term use which can work counter to reducing hs-CRP over the long run.
Via Google’s AI:
Ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID), can cause dysbiosis—an imbalance in the types and quantities of microbes in the gut. This occurs through several key mechanisms:
Damage to the intestinal barrier
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Reduced protective mucus: Ibuprofen works by inhibiting the cyclooxygenase (COX) enzymes that produce prostaglandins. Prostaglandins are critical for protecting the gut lining by promoting mucus production and regulating blood flow. By blocking them, ibuprofen thins the protective mucus layer, leaving the intestinal wall vulnerable to irritation and damage from stomach acid and other substances.
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Increased permeability: Research shows that regular NSAID use can increase intestinal permeability, leading to a condition known as “leaky gut”. This creates gaps in the intestinal lining that allow toxins, harmful bacteria, and undigested food particles to enter the bloodstream, triggering inflammation.
Changes in bacterial balance
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Encourages harmful bacteria: When the gut barrier is damaged, it can lead to an overgrowth of potentially harmful, pro-inflammatory bacteria, particularly Gram-negative species like Enterobacteriaceae (which includes E. coli). Studies of ibuprofen users have shown an enrichment of bacterial families such as Acidaminococcaceae and Enterobacteriaceae.
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Depletes beneficial bacteria: Frequent NSAID use may reduce the population of beneficial bacteria, such as those that produce short-chain fatty acids (SCFAs), which are vital for maintaining a healthy gut lining.
Impact on the microbiome’s function
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Bacterial translocation: By increasing intestinal permeability, ibuprofen enables bacteria to move from the gut into the surrounding mucosa and other parts of the body. This activates the immune system and can trigger a pro-inflammatory response.
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Exacerbates infections: Some studies indicate that NSAIDs may increase the severity of infections like Clostridium difficile, likely by altering the gut environment and microflora.
Risk factors and symptom management
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Dose and duration: The impact of ibuprofen on the gut is highly dependent on the dosage and how long you take it. Occasional use is generally safe for most people, but frequent or high-dose use significantly increases the risk of negative effects.
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Symptoms of gut distress: Gastrointestinal symptoms associated with regular ibuprofen use include gas, bloating, stomach pain, heartburn, and changes in bowel habits like diarrhea or constipation.
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Minimizing risk: If you need to take ibuprofen, you can reduce the gut-related risks by using the lowest possible dose, taking it with food, and avoiding prolonged use. For persistent pain or chronic conditions, discuss long-term pain management strategies with a doctor.
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Just in today…
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Nice…
Cocoa… dark chocolate is my favorite treat.
A day doesn’t go by for me without dark chocolate. 
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