Research finds low methionine and cysteine diet increases caloric burn in mice — Evidence Review
Published in eLife, by researchers from University of Southern Denmark, Cornell University
Researched by
— the AI search engine for science
Table of Contents
A new study from the University of Southern Denmark found that lowering methionine and cysteine in the diet of mice significantly increased calorie burning and weight loss, matching the effects of cold exposure. Related studies largely support these findings, indicating that restricting these amino acids may boost energy expenditure and improve metabolic health.
- Multiple mouse and human studies have shown that restricting methionine and cysteine increases energy expenditure, fat oxidation, and markers of metabolic health, consistent with the new findings 1 2 3 4 5 6 7 8 9.
- Evidence suggests that these effects are not due to reduced food intake or increased activity, but rather to increased thermogenesis and changes in fat metabolism, particularly in beige or subcutaneous fat tissue 2 4 7 8.
- Human trials are limited but indicate potential benefits for metabolic health from methionine and cysteine restriction, though the magnitude and mechanisms may differ from those observed in mice 1 9.
Study Overview and Key Findings
Interest in "diet-induced thermogenesis" has grown as researchers seek alternatives to cold exposure for obesity treatment. While previous approaches focused on pharmacological or environmental stimulation of calorie burning, this study investigated whether simply adjusting dietary amino acid content could replicate these effects. The research is especially timely given the popularity of plant-based diets, which are naturally lower in methionine and cysteine, and the ongoing search for sustainable, non-pharmacological obesity interventions.
| Property | Value |
|---|---|
| Organization | University of Southern Denmark, Cornell University |
| Journal Name | eLife |
| Authors | Philip Ruppert, Jan-Wilhelm Kornfeld, Aylin Güller, Marcus Rosendahl, Natasa Stanic |
| Population | Mice |
| Methods | Animal Study |
| Outcome | Caloric burn, weight loss |
| Results | Mice on a low methionine and cysteine diet burned 20% more calories. |
Literature Review: Related Studies
To contextualize these findings, we searched the Consensus scientific paper database, which contains over 200 million research papers. The following search queries were used to identify relevant literature:
- low methionine diet calorie burning
- cysteine effects on fat metabolism
- dietary manipulation weight loss mice studies
Literature Review Table
| Topic | Key Findings |
|---|---|
| How does methionine and cysteine restriction influence energy expenditure and fat metabolism? | - Methionine and cysteine restriction increases energy expenditure and fat oxidation in mice, and also reduces fat mass and improves metabolic health 2 3 4 5 7. - These effects are primarily due to increased thermogenesis and changes in adipose tissue metabolism, not reduced calorie intake or increased activity 2 4 7 8. |
| What is the evidence for translational potential in humans? | - Human studies show some benefits for metabolic health, including increased fat oxidation and improved biomarkers, but effects on energy expenditure and weight loss are less pronounced or require further validation 1 9. - Vegan and vegetarian diets, which are naturally low in methionine and cysteine, are associated with higher circulating FGF21 and potentially improved metabolic profiles 4 9. |
| What mechanisms underlie the metabolic changes with sulfur amino acid restriction? | - Increased FGF21 production, enhanced beige fat activation, reduced hepatic lipid synthesis, and altered gene expression in adipose tissue are key mechanisms 4 5 7 8 9. - Cysteine supplementation can reverse the beneficial effects of methionine restriction, highlighting the importance of both amino acids in regulating metabolism 6 7 8 10. |
| Are there risks or limitations to methionine and cysteine restriction? | - Excessive restriction can impair growth and induce essential amino acid deficiency responses in rodents 3. - Sex, duration, and extent of restriction may influence outcomes, and long-term safety in humans remains uncertain 2 3 9. |
How does methionine and cysteine restriction influence energy expenditure and fat metabolism?
The new study's findings that low methionine and cysteine intake increases thermogenesis and weight loss in mice are supported by multiple experimental studies. These studies show that restricting these amino acids leads to increased fat oxidation, higher energy expenditure, and reduced adiposity, primarily through metabolic adaptations in adipose tissue, rather than through calorie restriction.
- Methionine restriction raises energy expenditure and fat oxidation in obese and non-obese mice, resulting in reduced fat mass even when food intake is unchanged 2 3 4 5 7.
- Cysteine supplementation can reverse the anti-obesity effects of methionine restriction, indicating both amino acids play a role in regulating fat storage and metabolism 6 7 8 10.
- High cysteine intake promotes adiposity and adverse metabolic profiles in mice, supporting the view that lower dietary cysteine may aid weight loss 8 10.
- These effects are robust in rodents, but translation to humans is less clear, with metabolic benefits observed but not always accompanied by increased energy expenditure or significant weight loss 1 9.
What is the evidence for translational potential in humans?
While the metabolic effects of methionine and cysteine restriction are well-documented in animal models, evidence in humans is more limited. Small clinical trials and observational studies suggest some metabolic benefits, but results regarding energy expenditure and weight loss are mixed.
- Controlled trials in humans have reported increased fat oxidation and improvements in cardiometabolic biomarkers with methionine/cysteine restriction, but effects on total energy expenditure and body weight are less certain 1 9.
- Vegan and vegetarian diets, characterized by low methionine and cysteine content, are associated with higher FGF21 levels and improved metabolic markers, but causality remains to be established 4 9.
- Human participants generally tolerate short-term methionine and cysteine restriction, though long-term adherence and safety require further study 9.
- Differences in dietary habits, baseline health, and genetic background may affect the degree of benefit seen in human populations compared to animal models 1 9.
What mechanisms underlie the metabolic changes with sulfur amino acid restriction?
The metabolic effects of restricting methionine and cysteine stem from several interconnected mechanisms, including hormonal changes, alterations in fat tissue, and shifts in gene expression.
- Methionine/cysteine restriction increases circulating FGF21, a hormone that promotes energy expenditure and thermogenesis, especially in beige fat 4 5 7 9.
- Gene expression changes in adipose tissue and liver promote lipid oxidation, reduce lipogenesis, and lower inflammation, contributing to improved metabolic profiles 7 8 9.
- Cysteine supplementation can counteract the benefits of methionine restriction, highlighting the complex interplay between these sulfur amino acids 6 7 8 10.
- The extent of metabolic adaptation may depend on the degree and duration of restriction, as well as the balance of other dietary amino acids 2 3 5 7.
Are there risks or limitations to methionine and cysteine restriction?
Although sulfur amino acid restriction offers metabolic benefits in animal models, there are potential risks, particularly if restriction is too severe or prolonged.
- Rodent studies indicate that excessive methionine restriction (below 0.12%) can cause essential amino acid deficiency, growth impairment, and food aversion 3.
- Effects may differ by sex, age, and genetic background, and long-term impacts in humans are unknown 2 3 9.
- The optimal range for health benefits without adverse effects appears narrow, emphasizing the need for careful dietary design in future human studies 3 7 9.
- Translation to clinical recommendations awaits larger, longer-term human trials to assess safety, efficacy, and feasibility 1 9.
Future Research Questions
Despite promising results, significant knowledge gaps remain regarding the safety, mechanisms, and effectiveness of methionine and cysteine restriction in humans. Addressing these questions is essential before recommending such dietary modifications for obesity or metabolic disease treatment.
| Research Question | Relevance |
|---|---|
| Does methionine and cysteine restriction induce thermogenesis and weight loss in humans? | Human studies are needed to confirm whether the calorie-burning and weight loss effects seen in mice translate to people, as current evidence in humans is limited and inconclusive 1 9. |
| What are the long-term effects and safety of sulfur amino acid restriction in humans? | Most studies to date are short-term and in animals; long-term human studies are needed to assess safety, tolerability, and potential side effects of methionine and cysteine restriction 3 9. |
| How does methionine and cysteine restriction affect different types of adipose tissue in humans? | Rodent studies highlight the role of beige fat activation, but it is unclear whether similar mechanisms operate in human adipose tissue and whether these changes can be harnessed for obesity treatment 4 7 9. |
| Can functional foods naturally low in methionine and cysteine support weight management? | Developing practical dietary interventions or functional foods based on these findings could offer new, accessible strategies for obesity prevention and treatment 4 9. |
| Do methionine and cysteine restrictions augment the effects of existing weight loss medications? | Combining dietary amino acid restriction with pharmacological treatments like GLP-1 agonists could enhance weight loss, but this hypothesis remains to be tested in clinical trials 9. |