Condition
Blood Health
Blood health is how well your blood carries oxygen, helps defend against infection and keeps circulating, which depends on healthy red and white cells. The strongest evidence is for pegcetacoplan, which improved hemoglobin more than the standard drug eculizumab in a large trial in paroxysmal nocturnal hemoglobinuria. Beyond that, evidence is limited: chlorophyllin improved white blood cell counts in one trial of 105 people, but most other work is small or in animals.
Sources: PMID 33657294; PMID 35441351
- Updated
- How we grade
- 100 studies cited
- Supplements studied
- 4
- Medicines and peptides
- 2
- Graded outcomes
- 11
Evidence by supplement
- Strong
- Moderate
- Limited
- Very limited
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| White Blood Cell Count An RCT of 105 patients with leukopenia found sodium copper chlorophyllin tablets (60 patients) improved peripheral white blood cell counts over 1 month compared to leucogen and placebo controls. A separate animal study in aplastic anemia mice showed effects on mesenchymal stem cell function. Limited to a single human RCT. | Improves (the measure goes up) | Small effect | 4 studies | 105 people | ||
Studies that measured white blood cell count | ||||||
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Erythrocyte Membrane Integrity Human studies showed L-cysteine supplementation preserved erythrocyte membrane acetylcholinesterase and Na+,K+-ATPase activities and protected G6PD activity from reduction during exercise-induced oxidative stress. | Improves (the measure goes up) | Small effect | 2 studies | 40 people | ||
Studies that measured erythrocyte membrane integrity | ||||||
Essential fatty acid (EFA)
- Red Blood Cell Rheology: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Red Blood Cell Rheology A small human trial found that combined omega-3 and omega-6 EFA supplementation improved red blood cell deformability and rheological properties, which may support microcirculation. | Improves (the measure goes up) | Small effect | 3 studies | 20 people | ||
Histidine
- Iron Status: improves
- Hemoglobin Synthesis: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Iron Status Limited human research suggests histidine supplementation may improve iron status and enhance iron absorption in iron-deficiency anemia. Biochemically, histidine is critical for hemoglobin structure and oxygen binding, and animal studies confirm its importance in hemoglobin synthesis. Evidence remains preliminary with no large controlled trials. | Improves (the measure goes up) | Small effect | ||||
| Hemoglobin Synthesis Animal studies demonstrate histidine is essential for hemoglobin synthesis, and histidine deficiency causes growth retardation. The imidazole side chain of histidine plays a critical structural role in hemoglobin's oxygen-binding capacity. Human supplementation data supporting improved hemoglobin levels is very limited. | Improves (the measure goes up) | Small effect |
Prescription medicines and peptides studied, for context
Pegcetacoplan (Empaveli)
- Hemoglobin Improvement vs Eculizumab: improves
- Extravascular Hemolysis Control: improves
- Safety Profile: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Hemoglobin Improvement vs Eculizumab PEGASUS Phase III trial: Pegcetacoplan significantly superior to eculizumab for hemoglobin improvement (p<0.001). First therapy to demonstrate superiority over standard C5 inhibitor treatment in PNH. | Improves (the measure goes up) | Large effect | 16 studies | |||
| Extravascular Hemolysis Control Unique mechanism: C3 inhibition prevents C3b opsonization, controlling extravascular hemolysis that C5 inhibitors cannot address. Addresses key limitation of prior PNH treatments. | Improves (the measure goes up) | Large effect | 12 studies | |||
| Safety Profile Well-tolerated in clinical trials. Most common AEs: injection site reactions, infections. Requires vaccination against encapsulated bacteria (meningococcal, pneumococcal). Self-administered subcutaneously. | Improves (the measure goes up) | Moderate effect | 10 studies | |||
| Transfusion Independence PEGASUS trial: 85% of pegcetacoplan patients transfusion-free at 16 weeks vs 15% on eculizumab (p<0.001). Dramatic reduction in transfusion requirements. | Improves (the measure goes up) | Large effect | 9 studies | |||
| Complement-Inhibitor-Naive PNH PRINCE Phase III trial: Superior to supportive care in treatment-naive PNH patients. Achieved hemoglobin stabilization and LDH reduction. Approved for both naive and C5i-experienced patients. | Improves (the measure goes up) | Large effect | 9 studies |
Gramicidin
- Hemolytic Toxicity: worsens
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Hemolytic Toxicity SAFETY CONCERN: Highly hemolytic - cannot be administered systemically. Internal use contraindicated. Topical absorption negligible. Limits use to topical applications only. | Worsens (the measure goes up) | Large effect | 6 studies |
Key findings
- White Blood Cell CountImproves (the measure goes up)
- Erythrocyte Membrane IntegrityImproves (the measure goes up)
- Red Blood Cell RheologyImproves (the measure goes up)
Studies cited
100 studies from PubMed
- Lipid Composition of Nanocarriers Shapes Interactions of Cyclic Antimicrobial Peptide Gramicidin S with Their Membranes.
- Discovery of a potent ornithine-modified gramicidin S analogue against drug-resistant Staphylococcus aureus and Enterococcus faecalis with minimal red blood cell toxicity.
- Machine-Learning Approach to Increase the Potency and Overcome the Hemolytic Toxicity of Gramicidin S.
- Safety and efficacy of pegcetacoplan treatment for cold agglutinin disease and warm antibody autoimmune hemolytic anemia.
- Efficacy and Safety of Pegcetacoplan in Kidney Transplant Recipients With Recurrent Complement 3 Glomerulopathy or Primary Immune Complex Membranoproliferative Glomerulonephritis.
- Ravulizumab and other complement inhibitors for the treatment of autoimmune disorders.
- Pegcetacoplan for the treatment of warm autoimmune hemolytic anemia: a case report.
- Trial of Pegcetacoplan in C3 Glomerulopathy and Immune-Complex MPGN.
- Efficacy, Safety, and Quality of Life of Pegcetacoplan in Japanese Patients with Paroxysmal Nocturnal Hemoglobinuria Treated within the Phase 3 PEGASUS Trial.
- Ocular Adverse Events Associated with Pegcetacoplan and Avacincaptad Pegol for Geographic Atrophy: A Population-Based Pharmacovigilance Study.
- Efficacy and Safety Maintained up to 3 Years in Adults with Paroxysmal Nocturnal Hemoglobinuria Receiving Pegcetacoplan.
- Sterile Intraocular Inflammation Following Intravitreal Injections: Pathogenesis, Clinical Features, and Management.
- Visual Function Benefit After Treatment With Pegcetacoplan: Microperimetry Analysis From the Phase 3 Oaks Trial.
- Breakthrough hemolysis in paroxysmal nocturnal hemoglobinuria throughout clinical trials: from definition to clinical practice.
- Modifying Membranotropic Action of Antimicrobial Peptide Gramicidin S by Star-like Polyacrylamide and Lipid Composition of Nanocontainers.
- A New Gramicidin S Analogue with Potent Antibacterial Activity and Negligible Hemolytic Toxicity.
- Treatment of geographic atrophy: an update on data related to pegcetacoplan.
- Pegcetacoplan Treatment and Consensus Features of Geographic Atrophy Over 24 Months.
- Autoimmune Hemolytic Anemias: Challenges in Diagnosis and Therapy.
- Safety and Efficacy of Pegcetacoplan in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria over 48 Weeks: 307 Open-Label Extension Study.
- Complement inhibitors in pediatric kidney diseases: new therapeutic opportunities.
- Severe Intraocular Inflammation Following Intravitreal Faricimab.
- Hemolysis events in the phase 3 PEGASUS study of pegcetacoplan in patients with paroxysmal nocturnal hemoglobinuria.
- Pegcetacoplan: A New Opportunity for Complement Inhibition in PNH
- Pegcetacoplan (Syfovre) for geographic atrophy in age-related macular degeneration.
- Geographic atrophy: Mechanism of disease, pathophysiology, and role of the complement system.
- WITHDRAWN: Pegcetacoplan in the treatment of geographic atrophy.
- Pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY): two multicentre, randomised, double-masked, sham-controlled, phase 3 trials.
- Advancements in the treatment of geographic atrophy: focus on pegcetacoplan in age-related macular degeneration.
- Clinical Safety and Efficacy of Pegcetacoplan in a Phase 2 Study of Patients with C3 Glomerulopathy and Other Complement-Mediated Glomerular Diseases.
- Targeting complement in IgA nephropathy.
- Pegcetacoplan for Treating Paroxysmal Nocturnal Haemoglobinuria: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.
- Correction to: Pegcetacoplan: A Review in Paroxysmal Nocturnal Haemoglobinuria.
- Treatment of dry age-related macular degeneration: A review.
- Novel targeted C3 inhibitor pegcetacoplan for paroxysmal nocturnal hemoglobinuria
- Pegcetacoplan: A Review in Paroxysmal Nocturnal Haemoglobinuria
- Safety and efficacy of pegcetacoplan in paroxysmal nocturnal hemoglobinuria
- Association of Pegcetacoplan With Progression of Incomplete Retinal Pigment Epithelium and Outer Retinal Atrophy in Age-Related Macular Degeneration: A Post Hoc Analysis of the FILLY Randomized Clinical Trial.
- Pegcetacoplan treatment for geographic atrophy due to age-related macular degeneration: a plain language summary of the FILLY study.
- New Therapies for the Treatment of Warm Autoimmune Hemolytic Anemia.
- Safety and efficacy of pegcetacoplan in paroxysmal nocturnal hemoglobinuria.
- Pegcetacoplan in paroxysmal nocturnal hemoglobinuria: A systematic review on efficacy and safety.
- Pegcetacoplan versus eculizumab in patients with paroxysmal nocturnal haemoglobinuria (PEGASUS): 48-week follow-up of a randomised, open-label, phase 3, active-comparator, controlled trial.
- From discovery to approval: A brief history of the compstatin family of complement C3 inhibitors
- Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria
- Pegcetacoplan treatment in patients with paroxysmal nocturnal hemoglobinuria with suboptimal response to eculizumab: PRINCE study primary analysis
- Pegcetacoplan: First Approval
- Complement activation promoted by the lectin pathway mediates C3aR-dependent sarcoma progression and immunosuppression.
- Efficacy of topical drugs in the treatment of patients with acute inflammatory diseases of the pharynx
- Complement C3 Inhibitor Pegcetacoplan for Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Randomized Phase 2 Trial.
- Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis.
- New Insights in Autoimmune Hemolytic Anemia: From Pathogenesis to Therapy Stage 1.
- Topical (local) antibiotics for respiratory infections with sore throat: An antibiotic stewardship perspective
- The Multifaceted Antibacterial Mechanisms of the Pioneering Peptide Antibiotics Tyrocidine and Gramicidin S
- Gramicidin Lateral Distribution in Phospholipid Membranes: Fluorescence Phasor Plots and Statistical Mechanical Model.
- Structure, toxicity and antibiotic activity of gramicidin S and derivatives.
- Chemopreventive potential of chlorophyllin: a review of the mechanisms of action and molecular targets
- In vitro genotoxicity of mycotoxins ochratoxin A and fumonisin B(1) could be prevented by sodium copper chlorophyllin--implication to their genotoxic mechanism
- Topical Treatment With Liposomal Sodium Copper Chlorophyllin Complex in Subjects With Facial Redness and Erythematotelangiectatic Rosacea: Case Studies
- In vitro inhibition of hyaluronidase by sodium copper chlorophyllin complex and chlorophyllin analogs
- Effects of sodium copper chlorophyllin on mesenchymal stem cell function in aplastic anemia mice
- Sodium copper chlorophyllin (SCC) induces genetic damage in postmeiotic and somatic wing cells of Drosophila melanogaster
- Immunomodulatory and therapeutic effects of Hot-nature diet and co-supplemented hemp seed, evening primrose oils intervention in multiple sclerosis patients.
- Chlorophyll revisited: anti-inflammatory activities of chlorophyll a and inhibition of expression of TNF-α
- Anticarcinogenic effect of probiotic fermented milk and chlorophyllin on aflatoxin-B₁-induced liver carcinogenesis in rats
- Gene expression signature of DMBA-induced hamster buccal pouch carcinomas: modulation by chlorophyllin and ellagic acid
- Polycationic gramicidin S analogues with both high antibiotic activity and very low hemolytic activity.
- 'Inverted' analogs of the antibiotic gramicidin S with an improved biological profile.
- Effect of probiotic fermented milk and chlorophyllin on gene expressions and genotoxicity during AFB₁-induced hepatocellular carcinoma
- Perinatal programming of murine immune responses by polyunsaturated fatty acids.
- Essential fatty acids for dry eye: A review.
- Essential fatty acids in the treatment of dry eye.
- Essential fatty acids and attention-deficit-hyperactivity disorder: a systematic review.
- Gramicidin S and polymyxins: the revival of cationic cyclic peptide antibiotics
- Optimization of antimicrobial drug gramicidin S dosing regime using biosimulations.
- Essential fatty acids and their metabolites could function as endogenous HMG-CoA reductase and ACE enzyme inhibitors, anti-arrhythmic, anti-hypertensive, anti-atherosclerotic, anti-inflammatory, cytoprotective, and cardioprotective molecules.
- Do polyunsaturated fatty acids behave like an endogenous "polypill"?
- Interaction of gramicidin S and its aromatic amino-acid analog with phospholipid membranes.
- Protective effects of cysteine, methionine and vitamin C on the stomach in chronically alcohol treated rats.
- Chlorophylls as anti-carcinogens
- L-cysteine supplementation prevents exercise-induced alterations in human erythrocyte membrane acetylcholinesterase and Na+,K+-ATPase activities.
- Tardive dyskinesia and essential fatty acids.
- Beta-turn modified gramicidin S analogues containing arylated sugar amino acids display antimicrobial and hemolytic activity comparable to the natural product.
- The beneficial effect of L-cysteine supplementation on DNA oxidation induced by forced training.
- L-cysteine supplementation protects the erythrocyte glucose-6-phosphate dehydrogenase activity from reduction induced by forced training.
- Does ascorbate/L-Cys/L-Met mixture protect different parts of the rat brain against chronic alcohol toxicity?
- Protective effects of chlorophyllin in murine tumor models and in human volunteers
- Analysis of the therapeutic effect of sodium copper chlorophyllin tablet in treating 60 cases of leukopenia
- Essential fatty acids, DHA and human brain.
- Alcohol-induced oxidative stress and reduction in oxidation by ascorbate/L-cys/L-met in the testis, ovary, kidney, and lung of rat.
- A comprehensive review on chlorophylls and related applications
- Effects of the dietary supplements, activated charcoal and copper chlorophyllin, on urinary excretion of trimethylamine in Japanese trimethylaminuria patients
- Interaction of gramicidin derivatives with phospholipid monolayers.
- Effect of simultaneous administration of vitamin C, L-cysteine and vitamin E on the melanogenesis.
- The efficacy and safety of topical polymyxin B, neomycin and gramicidin for treatment of presumed bacterial corneal ulceration
- Structure-activity relationships of de novo designed cyclic antimicrobial peptides based on gramicidin S
- [Structural and functional characteristics of gramicidin S in connection with its antibiotic activity].
- Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer
- Membrane-bound structure and alignment of the antimicrobial beta-sheet peptide gramicidin S derived from angular and distance constraints by solid state 19F-NMR.
- Dieting, essential fatty acid intake, and depression.