Condition
Appetite Regulation
Appetite regulation is the body's hunger and fullness system, where hormones like ghrelin, leptin, GLP-1 and PYY pass signals between gut, brain and fat tissue. The evidence is strongest for glucomannan, a fiber that swells in the stomach, and for protein, while small trials of 5-HTP from Griffonia found more fullness and less eating. Those 5-HTP studies were tiny, and green tea extract showed no clear difference in ghrelin.
Sources: PMID 33209198; PMID 16023217
- Supplements studied
- 9
- Medicines and peptides
- 1
- Graded outcomes
- 9
- Trials
- 1
- People studied
- 1,639
Evidence by supplement
- Strong
- Moderate
- Limited
- Very limited
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Appetite and Food Intake Two small RCTs using Griffonia extract specifically (oral/sublingual spray, n=20 and n=27) showed significantly increased satiety and reduced BMI in overweight women. Three placebo-controlled 5-HTP trials by Cangiano et al. (n=19-25 each) demonstrated reduced food intake, decreased carbohydrate consumption, and weight loss in obese subjects, including those with type 2 diabetes (750 mg/day). An 8-week RCT in trained adults found 5-HTP may reduce body fat mass. | Improves (the measure goes down) | Moderate effect | 7 studies | 140 people | ||
Studies that measured appetite and food intake
| ||||||
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Appetite Reduction Consistently reduces food intake across multiple animal species via vagal afferent signaling and PPARα activation. Human observational studies link post-bariatric surgery OEA increases to metabolic improvements (PMID:30702457, PMID:25413674), but direct oral supplementation has not been validated in human trials. | Improves (the measure goes down) | Moderate effect | 4 studies | |||
Studies that measured appetite reduction
| ||||||
White Kidney Bean Extract
- Appetite: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Appetite Several human studies suggest appetite-suppressing effects. Spadafranca et al. (2013) found suppressed ghrelin rebound and lower desire to eat (p=0.02) in a small acute RCT (n=12). Luzzi et al. (2014) reported improved satiety and decreased appetite alongside weight loss in 60 overweight subjects over 12 weeks. Rondanelli et al. (2011) found improved hunger susceptibility scores with a combination of P. vulgaris and artichoke extract. | Improves (the measure goes down) | Small effect | 3 studies | 132 people | ||
Studies that measured appetite
| ||||||
Calcium Caseinate
- Satiety: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Satiety Casein increases satiety more than whey in some studies due to slower gastric emptying and prolonged gut hormone release. | Improves (the measure goes up) | Small effect | 100 people |
Jojoba
- Appetite Suppression (Oral - Safety Concerns): improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Appetite Suppression (Oral - Safety Concerns) In a controlled animal study, jojoba meal containing simmondsin (a cyanoglycoside) demonstrated satiating effects in dogs. A separate mouse study showed that orally administered jojoba wax is mostly excreted with minimal absorption. IMPORTANT: Oral jojoba consumption for appetite suppression is NOT recommended due to potential toxicity from simmondsin and related compounds. | Improves (the measure goes down) | Small effect | 2 studies | |||
Studies that measured appetite suppression (oral - safety concerns) | ||||||
Coleus forskohlii
- Appetite
- Weight: improves
- Blood glucose: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Appetite No effect | NoneNo effect | 30 people | ||||
| Weight | Improves (the measure goes down) | 3 studies | 30 people | |||
Studies that measured weight
| ||||||
| Blood glucose | Improves (the measure goes down) | 30 people | ||||
| Blood Pressure | Improves (the measure goes down) | 30 people | ||||
| Heart Rate | Improves (the measure goes down) | 30 people | ||||
| Hip Circumference | Improves (the measure goes down) | 30 people | ||||
| Insulin | Changes; see studies | 30 people | ||||
| Insulin Resistance | Improves (the measure goes down) | 30 people | ||||
| Waist circumference | Improves (the measure goes down) | 30 people | ||||
| Waist-Hip Ratio | Improves (the measure goes up) | 30 people | ||||
Green Tea Extract
- Ghrelin
- Leptin: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Ghrelin No effect | NoneNo effect | 927 people | ||||
| Leptin | Improves (the measure goes up) | 1 study | 927 people | |||
Whey Protein
- Appetite: changes; see studies
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Appetite | Changes; see studies | 1 study | 64 people | |||
Studies that measured appetite | ||||||
Resistant Starch
- Appetite: changes; see studies
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Appetite | Changes; see studies | 1 study | 264 people | |||
Prescription medicines and peptides studied, for context
Setmelanotide (Imcivree)
- Hunger Reduction: improves
- Hyperphagia Control: improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Hunger Reduction Significant improvements in hunger scores were observed in all cohorts (POMC, LEPR, and BBS) with setmelanotide treatment. | Improves (the measure goes up) | Large effect | 9 studies | |||
| Hyperphagia Control Setmelanotide reduced hyperphagia and obsessive focus on food in patients with genetic obesity syndromes, improving daily functioning. | Improves (the measure goes down) | Large effect | 9 studies |
Key findings
- Appetite and Food IntakeImproves (the measure goes down)
- Appetite ReductionImproves (the measure goes down)
- AppetiteImproves (the measure goes down)
Safety notes in the studies
- IMPORTANT: Oral jojoba consumption for appetite suppression is NOT recommended due to potential toxicity from simmondsin and related compounds.
The Appetite Regulation & Satiety Support protocol
2 primary supplements · 6 supporting supplements
- Glucomannan1–3 g before meals with plenty of water
- Protein Supplementation20–30 g protein at each meal; consider protein supplement if dietary protein is low
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Studies cited
100 studies from PubMed
- The contribution of baseline circulating endocannabinoids to individual differences in human pain sensitivity: a quantitative sensory testing study.
- Polymorphism of Melanocortin Receptor Genes-Association with Inflammatory Traits and Diseases.
- Real-life experience on efficacy and safety of setmelanotide treatment in prepubertal children.
- Adverse event profile of setmelanotide in obesity: an integrated assessment and systematic review using disproportionality analysis, case reports and meta-analysis.
- Real-World Efficacy and Safety of Setmelanotide in Adults With Monogenic or Syndromic Obesity: A Prospective Cohort Study.
- Risk of Glaucoma in Patients without Diabetes Using a Glucagon-Like Peptide 1 Receptor Agonist.
- Setmelanotide in patients aged 2-5 years with rare MC4R pathway-associated obesity (VENTURE): a 1 year, open-label, multicenter, phase 3 trial.
- Current and Emerging Parenteral and Peroral Medications for Weight Loss: A Narrative Review.
- Management of Acquired Hypothalamic Obesity After Childhood-Onset Craniopharyngioma-A Narrative Review.
- 5-HTP supplementation and sleep quality and gut microbiota in older adults
- Topical application of jojoba (Simmondsia chinensis L.) wax enhances the synthesis of pro-collagen III and hyaluronic acid and reduces inflammation in the ex-vivo human skin organ culture model
- Approach to Obesity Treatment in Primary Care: A Review.
- Setmelanotide for the treatment of acquired hypothalamic obesity: a phase 2, open-label, multicentre trial.
- Proprietary alpha-amylase inhibitor formulation from white kidney bean (Phaseolus vulgaris L.) promotes weight and fat loss: a 12-week, double-blind, placebo-controlled, randomized trial
- The effect of 5-hydroxytryptophan on body composition in exercise-trained adults
- Quality of life improvements following one year of setmelanotide in children and adult patients with Bardet-Biedl syndrome: phase 3 trial results
- Interview-Based Patient- and Caregiver-Reported Experiences of Hunger and Improved Quality of Life with Setmelanotide Treatment in Bardet-Biedl Syndrome
- An evaluation of setmelanotide injection for chronic weight management in adult and pediatric patients with obesity due to Bardet-Biedl syndrome
- Setmelanotide: a promising advancement for pediatric patients with rare forms of genetic obesity
- Efficacy and Safety of Setmelanotide, a Melanocortin-4 Receptor Agonist, for Obese Patients: A Systematic Review and Meta-Analysis
- Efficacy and Safety of Setmelanotide, a Melanocortin-4 Receptor Agonist, for Obese Patients: A Systematic Review and Meta-Analysis.
- An update on peptide-based therapies for type 2 diabetes and obesity.
- Clinical Trials in Prader-Willi Syndrome: A Review.
- N-oleoylethanolamide treatment of lymphoblasts deficient in Tafazzin improves cell growth and mitochondrial morphology and dynamics.
- Setmelanotide for controlling weight and hunger in Bardet-Biedl syndrome
- Setmelanotide: A Novel Targeted Treatment for Monogenic Obesity
- Drugs for Treating Obesity.
- Quality of life outcomes in two phase 3 trials of setmelanotide in patients with obesity due to LEPR or POMC deficiency.
- Natural History of Obesity Due to POMC, PCSK1, and LEPR Deficiency and the Impact of Setmelanotide.
- A systematic review of licensed weight-loss medications in treating antipsychotic-induced weight gain and obesity in schizophrenia and psychosis.
- Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period.
- White common bean extract remodels the gut microbiota and ameliorates type 2 diabetes and its complications: A randomized double-blinded placebo-controlled trial
- Daily Intake of a Phaseolus vulgaris L. Snack Bar Attenuates Hypertriglyceridemia and Improves Lipid Metabolism-Associated Plasma Proteins in Mexican Women
- From forest to pharmacy: Should we be depressed about a sustainable Griffonia simplicifolia (Fabaceae) seed supply chain?
- 5-Hydroxytryptophan for REM sleep behavior disorder in Parkinson's disease
- Ameliorative effects of jojoba oil on fipronil-induced hepatorenal- and neuro-toxicity: the antioxidant status and apoptotic markers expression in rats
- Anti-Herpes Simplex 1 Activity of Simmondsia chinensis (Jojoba) Wax
- Pharmacological Blockade of PPARα Exacerbates Inflammatory Pain-Related Impairment of Spatial Memory in Rats.
- N-acylethanolamine regulation of TLR3-induced hyperthermia and neuroinflammatory gene expression: A role for PPARα.
- The efficacy and safety of setmelanotide in individuals with Bardet-Biedl syndrome or Alström syndrome: Phase 3 trial design
- The melanocortin pathway and energy homeostasis: From discovery to obesity therapy.
- Pharmacotherapy of obesity: An update.
- Next Generation Antiobesity Medications: Setmelanotide, Semaglutide, Tirzepatide and Bimagrumab: What do They Mean for Clinical Practice?
- Setmelanotide (Imcivree) for rare genetic forms of obesity.
- 5-Hydroxytryptophan (5-HTP): Natural occurrence, analysis, biosynthesis, biotechnology, physiology and toxicology
- Oea Signaling Pathways and the Metabolic Benefits of Vertical Sleeve Gastrectomy.
- Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials
- Effect of setmelanotide, a melanocortin-4 receptor agonist, on obesity in Bardet-Biedl syndrome
- Setmelanotide: what does it mean for clinical care of patients with obesity?
- Regular intake of white kidney beans extract (Phaseolus vulgaris L.) induces weight loss compared to placebo in obese human subjects
- It's No Has Bean: A Review of the Effects of White Kidney Bean Extract on Body Composition and Metabolic Health
- Setmelanotide treatment in a 2-year-old patient with POMC deficiency
- Insights into the Allosteric Mechanism of Setmelanotide (RM-493) as a Potent and First-in-Class Melanocortin-4 Receptor (MC4R) Agonist To Treat Rare Genetic Disorders of Obesity through an in Silico Approach.
- Setmelanotide, a Novel, Selective Melanocortin Receptor-4 Agonist Exerts Anti-inflammatory Actions in Astrocytes and Promotes an Anti-inflammatory Macrophage Phenotype.
- A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults
- N-oleoylethanolamide suppresses intimal hyperplasia after balloon injury in rats through AMPK/PPARα pathway.
- Profiling plasma N-Acylethanolamine levels and their ratios as a biomarker of obesity and dysmetabolism.
- Systematic Review and Meta-Analysis of a Proprietary Alpha-Amylase Inhibitor from White Bean (Phaseolus vulgaris L.) on Weight and Fat Loss in Humans
- Pharmacological inhibition of FAAH modulates TLR-induced neuroinflammation, but not sickness behaviour: An effect partially mediated by central TRPV1.
- Adjunctive 5-hydroxytryptophan slow-release for treatment-resistant depression: clinical and pre-clinical rationale
- Proof of Concept for POMC Deficiency: First Experience with Setmelanotide Treatment
- Griffonia simplicifolia and magnesium for motion sickness in children
- Gastric bypass in morbid obese patients is associated with reduction in adipose tissue inflammation via N-oleoylethanolamide (OEA)-mediated pathways.
- Synthesis and evaluation of fatty acid amides on the N-oleoylethanolamide-like activation of peroxisome proliferator activated receptor α.
- Weight reduction and maintenance with IQP-PV-101: a 12-week randomized controlled study with a 24-week open label period
- Beanblock (standardized dry extract of Phaseolus vulgaris) in mildly overweight subjects: a pilot study
- Jojoba in dermatology: a succinct review
- Phaseolus vulgaris extract affects glycometabolic and appetite control in healthy human subjects
- Presleep protein ingestion to improve the skeletal muscle adaptive response to exercise training
- Griffonia simplicifolia oral spray for satiety in overweight women
- Anxiolytic-like effect of Griffonia simplicifolia Baill. seed extract in rats
- Wound healing properties of jojoba liquid wax: an in vitro study
- The efficacy of Phaseolus vulgaris as a weight-loss supplement: a systematic review and meta-analysis of randomised clinical trials
- Appetite control and glycaemia reduction in overweight subjects treated with a combination of two highly standardized extracts from Phaseolus vulgaris and Cynara scolymus
- A proprietary alpha-amylase inhibitor from white bean (Phaseolus vulgaris): a review of clinical studies on weight loss and glycemic control
- Satiety and amino-acid profile in overweight women after a new treatment using a natural plant extract sublingual spray formulation
- Lowering the glycemic index of white bread using a white bean extract
- Evaluation of additive effects of hydrolyzed jojoba (Simmondsia chinensis) esters and glycerol: a preliminary study
- Actions of 3-methyl-N-oleoyldopamine, 4-methyl-N-oleoyldopamine and N-oleoylethanolamide on the rat TRPV1 receptor in vitro and in vivo.
- 'Entourage' effects of N-palmitoylethanolamide and N-oleoylethanolamide on vasorelaxation to anandamide occur through TRPV1 receptors.
- A dietary supplement containing standardized Phaseolus vulgaris extract influences body composition of overweight men and women
- Blocking carbohydrate absorption and weight loss: a clinical trial using a proprietary fractionated white bean extract
- Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan
- Anti-inflammatory effects of jojoba liquid wax in experimental models
- Ingestion of casein and whey proteins result in muscle anabolism after resistance exercise
- Blocking carbohydrate absorption and weight loss: a clinical trial using Phase 2 brand proprietary fractionated white bean extract
- Casein and whey exert different effects on plasma amino acid profiles, gastrointestinal hormone secretion and appetite
- 5-HTP and tryptophan for depression: a systematic review
- The satiating effect of a diet containing jojoba meal (Simmondsia chinensis) in dogs
- Slow and fast dietary proteins differently modulate postprandial protein accretion
- Primary fibromyalgia syndrome and 5-hydroxy-L-tryptophan: a 90-day open study
- Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome
- Effect of a serotonin precursor and uptake inhibitor in anxiety disorders: a double-blind comparison of 5-hydroxytryptophan, clomipramine and placebo
- 5-Hydroxytryptophan versus methysergide in the prophylaxis of migraine
- L-5-hydroxytryptophan in childhood migraine prophylaxis: a double-blind crossover study
- Absorption and distribution of orally administered jojoba wax in mice
- Protective effect of forskolin in acetylcholine provocation in healthy probands. Comparison of 2 doses with fenoterol and placebo
- Effects of coleus forskohlii supplementation on body composition and hematological profiles in mildly overweight women
- Coleus forskohlii Extract Supplementation in Conjunction with a Hypocaloric Diet Reduces the Risk Factors of Metabolic Syndrome in Overweight and Obese Subjects: A Randomized Controlled Trial
- The effects of forskolin eye drops on intra-ocular pressure