Project Details
Description
ERC-Consolidator grant 649021
STUDY SUMMARY
Cardiovascular disease (CVD), type 2 diabetes (T2D) and obesity, collectively referred to as cardiometabolic disease (CMD), together with cancer are the major morbidities and causes of death. With few exceptions, research on CMD and cancer is funded, studied and clinically applied separately without fully taking advantage of knowledge on common pathways and treatment targets through interdisciplinary synergies. Investigating the complex interactions between dietary factors, genetic risk factors, circulating biomarkers and gut and oral microbiota constitution in a comprehensive prospective cohort study design is a crucial first step to allow for subsequent intervention studies. The purpose of this proposal is to provide novel intervention strategies aiming to more effective prevention of cardiometabolic disease and cancer by:
- Providing novel understanding of causal connections between cardiometabolic traits and incidence of T2D, CVD and cancer,
- Providing novel understanding of interactions between genetic and dietary risk factors for cardiometabolic disease and
- Clarifying their connection to gut and oral microbiota and cancer.
OVERALL OBJECTIVES
TASK 1. To investigate causality between genetic risk factors for cardiometabolic traits and future incidence of T2D, CVD, cancer (total and subtypes of common forms) and mortality (total, CVD- and cancer mortality), searching for connecting and disconnecting causal factors.
TASK 2. To investigate how gut and oral microbiome are regulated by dietary factors, gut satiety peptides and host genetics, and how such connections relate to the risk of cardiometabolic diseases and cancer, in a large population.
TASK 3. To understand the role of diet and gene-diet interactions of importance for cardiometabolic disease and cancer aiming to better nutrition recommendations.
RESULTS
TASK 1
NOVEL BIOMARKERS
- We have in the Malmö Diet and Cancer Study (MDCS) identified several novel biomarkers of kidney function (1-4).
CONNECTION BETWEEN CARDIOMETABOLIC DISEASE AND CANCER
- We have described that comorbid type 2 diabetes and adiposity associate with a marked increased risk of obesity-related cancers and cancer mortality (5)
- We have by MR provided evidence for causal, inverse association between serum triglycerides and overall cancer risk and that LDLC-lowering effect of statins may increase prostate cancer risk (6).
- We have performed a first MR study for stroke subtypes and found that LDL cholesterol lowering is likely to prevent stroke due to large artery atherosclerosis but may not prevent small artery occlusion nor cardioembolic strokes (7).
TASK 2
GUT AND ORAL MICROBIOME IN A LARGE POPULATION
- A major effort of BIOMENDELIAN was the metagenomic sequencing of microbial DNA from fecal samples of 2200 MOS and 5007 SCAPIS-Malmö participants at Clinical Microbiomics (CM, Copenhagen). The data processing by bioinformatics pipelines for delivery of bacterial and virome taxonomy, gene annotations and functional pathways was finished in June 2020.
- In our first publication with human gut microbiota data and metabolomics data in the MOS study our results highlight a metabolic plasma profile that is dominated by high levels of glutamate and branched chain amino acids, which associated with obesity status and specific gut microbiota features. Further, our results indicate that the obesity related metabolite profile may be mediated by gut microbiota (8).
- We also identified a dietary pattern that associated with lower occurrence of prediabetes, as well as with a higher abundance of the bacterial genera Roseburia in the gut (9).
TASK 3ROLE OF DIET AND GENE-DIET INTERACTIONS OF IMPORTANCE FOR CARDIOMETABOLIC DISEASE AND CANCER
- We observed a significant interaction between a genetic variation in AMY1 gene and starch intake on BMI and body fat percentage (10).
- In another study we show that all individuals, whether at high or low genetic risk, would benefit from favorable food choices (11).
In addition to publications 1-11, nine other publications related to BIOMENDELIAN have been published (12-20)
PROGRESS BEYOND THE STATE OF THE ART AND EXPECTED RESULTS
Our prospective studies of 12,200 Swedish participants have more power and will cover a much larger proportion of the inter-individual variability of the gut microbiome than earlier studies. Unique to our metagenomic approach is the possibility for strain level resolution and tracking of phages. Novelty lies additionally in the metagenomic approach, which is beyond the state of the art in precision and coverage and allows a) strain level resolution, b) mapping of interrelationships between bacteria and phages, c) characterization of the individualized variability of gut microbiome in large population, and d) identification of compositional and functional elements and bacterial metabolites predisposing to risk of obesity, T2D and CVD. Further originality lies in the combination of clinical unique cardiometabolic phenotyping, plasma metabolome data, environmental (diet, medication etc.) data, and usage of novel data integration and causal interference approaches utilizing MR approach of genetic data.
PUBLICATIONS
1. Schulz CA, Persson M, Christensson A, Hindy G, Almgren P, Nilsson PM, Melander O, Engström G, Orho-Melander M. Soluble Urokinase-type Plasminogen Activator Receptor (suPAR) and Impaired Kidney Function in the Population-based Malmö Diet and Cancer Study. Kidney Int Rep. 2017; 2:239-247. (IF 2.26, citations 17)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362148/
2. Schulz CA, Christensson A, Ericson U, Almgren P, Hindy G, Nilsson PM, Struck J, Bergmann A, Melander O, Orho-Melander M. High Level of Fasting Plasma Proenkephalin-A Predicts Deterioration of Kidney Function and Incidence of CKD. J Am Soc Nephrol. 2017; 28:291-303. (IF 9.27, citations 15)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5198273/
3. Schulz CA, Engström G, Christensson A, Nilsson PM, Melander O, Orho-Melander M. Genetic Predisposition for Renal Dysfunction and Incidence of CKD in the Malmö Diet and Cancer Study. Kidney Int Rep. 2019; 4:1143-1151. (IF 2.26, citations 1)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698292/
4. Schulz CA, Engström G, Nilsson J, Almgren P, Petkovic M, Christensson A, Nilsson PM, Melander O, Orho-Melander M. Plasma kidney injury molecule-1 (p-KIM-1) levels and deterioration of kidney function over 16 years. Nephrol Dial Transplant. 2019; 35:265-273. (IF 4.09, citations 6)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049260/
5. Drake I, Gullberg B, Sonestedt E, Stocks T, Bjartell A, Wirfält E, Wallström P, Orho-Melander M. Type 2 diabetes, adiposity and cancer morbidity and mortality risk taking into account competing risk of noncancer deaths in a prospective cohort setting. Int J Cancer. 2017; 141:1170-1180. (IF 5.15, citations 8)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678678/
6. Orho-Melander M, Hindy G, Borgquist S, Schulz CA, Manjer J, Melander O, Stocks T. Blood lipid genetic scores, the HMGCR gene and cancer risk: a Mendelian randomization study. Int J Epidemiol. 2017; 47:495-505. (IF 7.34, citations 5)
https://academic.oup.com/ije/article/47/2/495/4641872
7. Hindy G, Engström G, Larsson SC, Traylor M, Markus HS, Melander M, Orho-Melander M for the Stroke Genetics Network (SiGN). Role of Blood Lipids in the Development of Ischemic Stroke and its Subtypes: a Mendelian Randomization Study. Stroke 2018; 49:820-827. (IF 6.03, citations 31)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895121/
8. Ottosson F*, Brunkwall L*, Ericson U, Nilsson PM, Almgren P, Fernandez C, Melander O and Orho-Melander M. Connection between BMI related plasma metabolite profile and gut microbiota. J Clin Endocrin Metab 2018; 103:1491-1501. (IF 5.61, citations 54)
https://academic.oup.com/jcem/article/103/4/1491/4834036
9. Ericson U, Brunkwall L, Hellstrand S, Nilsson PM, Orho-Melander M. A Health-Conscious Food Pattern Is Associated with Prediabetes and Gut Microbiota in the Malmö Offspring Study. J Nutr. 2020; 150:861-872. (IF 4.28, citation 2)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138670/
10. Rukh G, Ericson U, Andersson-Assarsson J, Orho-Melander M, Sonestedt E. Dietary starch intake modifies the relation between copy number variation in the salivary amylase gene and BMI. Am J Clin Nutr. 2017; 106:256-262. (IF 6.77, citations 17) https://academic.oup.com/ajcn/article/106/1/256/4569812
11. Ericson U, Hindy G, Drake I, Schulz CA, Brunkwall L, Hellstrand S, Almgren P, Orho-Melander M. Dietary and genetic risk scores and incidence of type 2 diabetes. Genes & Nutrition. 2018; 13:13. (IF 2.79, citations 13)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956794/
12. Brunkwall L, Orho-Melander M. The gut microbiome as a target for prevention and treatment of hyperglycaemia in type 2 diabetes: from current human evidence to future possibilities. Diabetologia. 2017; 60:943-951. (IF 7.11, citations 97)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5423958/
13. Drake I, Hindy G, Ericson U, Orho-Melander M. A prospective study of dietary and supplemental zinc intake and risk of type 2 diabetes depending on genetic variation in SLC30A8. Genes Nutr. 2017;12:30-35. (IF 2.79, citations 9) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661924/
14. Ericson U, Brunkwall L, Alves Dias J, Drake I, Hellstrand S, Gullberg B, Sonestedt E, Nilsson PM, Wirfält E, Orho-Melander M. Food patterns in relation to weight change and incidence of type 2 diabetes, coronary events and stroke in the Malmö Diet and Cancer cohort. Eur J Nutr 2018; 58:1801-1814. (IF 4.45, citations 8)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647222/
15. Drake I, Sonestedt E, Ericson U, Wallström P, Orho-Melander M. A Western dietary pattern is prospectively associated with cardio-metabolic traits and incidence of the metabolic syndrome. Br J Nutr. 2018; 119:1168-1176. (IF 3.33, citations 19)
https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/western-dietary-pattern-is-prospectively-associated-with-cardiometabolic-traits-and-incidence-of-the-metabolic-syndrome/27E9CD3FE973847C9EFC120C2CAFFA4B
16. Hindy G, Åkesson K, Melander O, Aragam K, Haas M, Kathiresan S, Nilsson PM, Kadam UT, Orho-Melander M. Cardiometabolic polygenic risk scores and osteoarthritis outcomes: a Mendelian randomization study from the Malmӧ Diet and Cancer Study and the UK BioBank. Arthritis & Rheumatology. 2019; 71:925-934. (IF 9.00, citations 3)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563114/
17. Dimovski K, Orho-Melander M, Drake I. A favorable lifestyle lowers the risk of coronary artery disease consistently across strata of non-modifiable risk factors in a population-based cohort. BMC Public Health. 2019; 19:1575. (IF 2.69, citations 2)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882082/
18. Drake I, Dias JA, Teleka S, Stocks T, Orho-Melander M. Lifestyle and cancer incidence and mortality risk depending on family history of cancer in two prospective cohorts. Int J Cancer. 2020; 146:1198-1207. (IF 5.14, citations 0)
https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.32397
19. Ramne S, Gray N, Hellstrand S, Brunkwall L, Enhörning S, Nilsson PM, Engström G, Orho-Melander M, Ericson U, Kuhnle GGC, Sonestedt E. Comparing Self-Reported Sugar Intake With the Sucrose and Fructose Biomarker From Overnight Urine Samples in Relation to Cardiometabolic Risk Factors. Front Nutr. 2020; 7:62. (IF 3.36, citations 1)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218081/
20. Smith E, Ottosson F, Hellstrand S, Ericson U, Orho-Melander M, Fernandez C, Melander O. Ergothioneine is associated with reduced mortality and decreased risk of cardiovascular disease. Heart. 2020; 106:691-697. (IF 5.42, citations 5)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229907/
STUDY SUMMARY
Cardiovascular disease (CVD), type 2 diabetes (T2D) and obesity, collectively referred to as cardiometabolic disease (CMD), together with cancer are the major morbidities and causes of death. With few exceptions, research on CMD and cancer is funded, studied and clinically applied separately without fully taking advantage of knowledge on common pathways and treatment targets through interdisciplinary synergies. Investigating the complex interactions between dietary factors, genetic risk factors, circulating biomarkers and gut and oral microbiota constitution in a comprehensive prospective cohort study design is a crucial first step to allow for subsequent intervention studies. The purpose of this proposal is to provide novel intervention strategies aiming to more effective prevention of cardiometabolic disease and cancer by:
- Providing novel understanding of causal connections between cardiometabolic traits and incidence of T2D, CVD and cancer,
- Providing novel understanding of interactions between genetic and dietary risk factors for cardiometabolic disease and
- Clarifying their connection to gut and oral microbiota and cancer.
OVERALL OBJECTIVES
TASK 1. To investigate causality between genetic risk factors for cardiometabolic traits and future incidence of T2D, CVD, cancer (total and subtypes of common forms) and mortality (total, CVD- and cancer mortality), searching for connecting and disconnecting causal factors.
TASK 2. To investigate how gut and oral microbiome are regulated by dietary factors, gut satiety peptides and host genetics, and how such connections relate to the risk of cardiometabolic diseases and cancer, in a large population.
TASK 3. To understand the role of diet and gene-diet interactions of importance for cardiometabolic disease and cancer aiming to better nutrition recommendations.
RESULTS
TASK 1
NOVEL BIOMARKERS
- We have in the Malmö Diet and Cancer Study (MDCS) identified several novel biomarkers of kidney function (1-4).
CONNECTION BETWEEN CARDIOMETABOLIC DISEASE AND CANCER
- We have described that comorbid type 2 diabetes and adiposity associate with a marked increased risk of obesity-related cancers and cancer mortality (5)
- We have by MR provided evidence for causal, inverse association between serum triglycerides and overall cancer risk and that LDLC-lowering effect of statins may increase prostate cancer risk (6).
- We have performed a first MR study for stroke subtypes and found that LDL cholesterol lowering is likely to prevent stroke due to large artery atherosclerosis but may not prevent small artery occlusion nor cardioembolic strokes (7).
TASK 2
GUT AND ORAL MICROBIOME IN A LARGE POPULATION
- A major effort of BIOMENDELIAN was the metagenomic sequencing of microbial DNA from fecal samples of 2200 MOS and 5007 SCAPIS-Malmö participants at Clinical Microbiomics (CM, Copenhagen). The data processing by bioinformatics pipelines for delivery of bacterial and virome taxonomy, gene annotations and functional pathways was finished in June 2020.
- In our first publication with human gut microbiota data and metabolomics data in the MOS study our results highlight a metabolic plasma profile that is dominated by high levels of glutamate and branched chain amino acids, which associated with obesity status and specific gut microbiota features. Further, our results indicate that the obesity related metabolite profile may be mediated by gut microbiota (8).
- We also identified a dietary pattern that associated with lower occurrence of prediabetes, as well as with a higher abundance of the bacterial genera Roseburia in the gut (9).
TASK 3ROLE OF DIET AND GENE-DIET INTERACTIONS OF IMPORTANCE FOR CARDIOMETABOLIC DISEASE AND CANCER
- We observed a significant interaction between a genetic variation in AMY1 gene and starch intake on BMI and body fat percentage (10).
- In another study we show that all individuals, whether at high or low genetic risk, would benefit from favorable food choices (11).
In addition to publications 1-11, nine other publications related to BIOMENDELIAN have been published (12-20)
PROGRESS BEYOND THE STATE OF THE ART AND EXPECTED RESULTS
Our prospective studies of 12,200 Swedish participants have more power and will cover a much larger proportion of the inter-individual variability of the gut microbiome than earlier studies. Unique to our metagenomic approach is the possibility for strain level resolution and tracking of phages. Novelty lies additionally in the metagenomic approach, which is beyond the state of the art in precision and coverage and allows a) strain level resolution, b) mapping of interrelationships between bacteria and phages, c) characterization of the individualized variability of gut microbiome in large population, and d) identification of compositional and functional elements and bacterial metabolites predisposing to risk of obesity, T2D and CVD. Further originality lies in the combination of clinical unique cardiometabolic phenotyping, plasma metabolome data, environmental (diet, medication etc.) data, and usage of novel data integration and causal interference approaches utilizing MR approach of genetic data.
PUBLICATIONS
1. Schulz CA, Persson M, Christensson A, Hindy G, Almgren P, Nilsson PM, Melander O, Engström G, Orho-Melander M. Soluble Urokinase-type Plasminogen Activator Receptor (suPAR) and Impaired Kidney Function in the Population-based Malmö Diet and Cancer Study. Kidney Int Rep. 2017; 2:239-247. (IF 2.26, citations 17)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362148/
2. Schulz CA, Christensson A, Ericson U, Almgren P, Hindy G, Nilsson PM, Struck J, Bergmann A, Melander O, Orho-Melander M. High Level of Fasting Plasma Proenkephalin-A Predicts Deterioration of Kidney Function and Incidence of CKD. J Am Soc Nephrol. 2017; 28:291-303. (IF 9.27, citations 15)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5198273/
3. Schulz CA, Engström G, Christensson A, Nilsson PM, Melander O, Orho-Melander M. Genetic Predisposition for Renal Dysfunction and Incidence of CKD in the Malmö Diet and Cancer Study. Kidney Int Rep. 2019; 4:1143-1151. (IF 2.26, citations 1)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698292/
4. Schulz CA, Engström G, Nilsson J, Almgren P, Petkovic M, Christensson A, Nilsson PM, Melander O, Orho-Melander M. Plasma kidney injury molecule-1 (p-KIM-1) levels and deterioration of kidney function over 16 years. Nephrol Dial Transplant. 2019; 35:265-273. (IF 4.09, citations 6)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049260/
5. Drake I, Gullberg B, Sonestedt E, Stocks T, Bjartell A, Wirfält E, Wallström P, Orho-Melander M. Type 2 diabetes, adiposity and cancer morbidity and mortality risk taking into account competing risk of noncancer deaths in a prospective cohort setting. Int J Cancer. 2017; 141:1170-1180. (IF 5.15, citations 8)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678678/
6. Orho-Melander M, Hindy G, Borgquist S, Schulz CA, Manjer J, Melander O, Stocks T. Blood lipid genetic scores, the HMGCR gene and cancer risk: a Mendelian randomization study. Int J Epidemiol. 2017; 47:495-505. (IF 7.34, citations 5)
https://academic.oup.com/ije/article/47/2/495/4641872
7. Hindy G, Engström G, Larsson SC, Traylor M, Markus HS, Melander M, Orho-Melander M for the Stroke Genetics Network (SiGN). Role of Blood Lipids in the Development of Ischemic Stroke and its Subtypes: a Mendelian Randomization Study. Stroke 2018; 49:820-827. (IF 6.03, citations 31)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895121/
8. Ottosson F*, Brunkwall L*, Ericson U, Nilsson PM, Almgren P, Fernandez C, Melander O and Orho-Melander M. Connection between BMI related plasma metabolite profile and gut microbiota. J Clin Endocrin Metab 2018; 103:1491-1501. (IF 5.61, citations 54)
https://academic.oup.com/jcem/article/103/4/1491/4834036
9. Ericson U, Brunkwall L, Hellstrand S, Nilsson PM, Orho-Melander M. A Health-Conscious Food Pattern Is Associated with Prediabetes and Gut Microbiota in the Malmö Offspring Study. J Nutr. 2020; 150:861-872. (IF 4.28, citation 2)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138670/
10. Rukh G, Ericson U, Andersson-Assarsson J, Orho-Melander M, Sonestedt E. Dietary starch intake modifies the relation between copy number variation in the salivary amylase gene and BMI. Am J Clin Nutr. 2017; 106:256-262. (IF 6.77, citations 17) https://academic.oup.com/ajcn/article/106/1/256/4569812
11. Ericson U, Hindy G, Drake I, Schulz CA, Brunkwall L, Hellstrand S, Almgren P, Orho-Melander M. Dietary and genetic risk scores and incidence of type 2 diabetes. Genes & Nutrition. 2018; 13:13. (IF 2.79, citations 13)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956794/
12. Brunkwall L, Orho-Melander M. The gut microbiome as a target for prevention and treatment of hyperglycaemia in type 2 diabetes: from current human evidence to future possibilities. Diabetologia. 2017; 60:943-951. (IF 7.11, citations 97)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5423958/
13. Drake I, Hindy G, Ericson U, Orho-Melander M. A prospective study of dietary and supplemental zinc intake and risk of type 2 diabetes depending on genetic variation in SLC30A8. Genes Nutr. 2017;12:30-35. (IF 2.79, citations 9) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661924/
14. Ericson U, Brunkwall L, Alves Dias J, Drake I, Hellstrand S, Gullberg B, Sonestedt E, Nilsson PM, Wirfält E, Orho-Melander M. Food patterns in relation to weight change and incidence of type 2 diabetes, coronary events and stroke in the Malmö Diet and Cancer cohort. Eur J Nutr 2018; 58:1801-1814. (IF 4.45, citations 8)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647222/
15. Drake I, Sonestedt E, Ericson U, Wallström P, Orho-Melander M. A Western dietary pattern is prospectively associated with cardio-metabolic traits and incidence of the metabolic syndrome. Br J Nutr. 2018; 119:1168-1176. (IF 3.33, citations 19)
https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/western-dietary-pattern-is-prospectively-associated-with-cardiometabolic-traits-and-incidence-of-the-metabolic-syndrome/27E9CD3FE973847C9EFC120C2CAFFA4B
16. Hindy G, Åkesson K, Melander O, Aragam K, Haas M, Kathiresan S, Nilsson PM, Kadam UT, Orho-Melander M. Cardiometabolic polygenic risk scores and osteoarthritis outcomes: a Mendelian randomization study from the Malmӧ Diet and Cancer Study and the UK BioBank. Arthritis & Rheumatology. 2019; 71:925-934. (IF 9.00, citations 3)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563114/
17. Dimovski K, Orho-Melander M, Drake I. A favorable lifestyle lowers the risk of coronary artery disease consistently across strata of non-modifiable risk factors in a population-based cohort. BMC Public Health. 2019; 19:1575. (IF 2.69, citations 2)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882082/
18. Drake I, Dias JA, Teleka S, Stocks T, Orho-Melander M. Lifestyle and cancer incidence and mortality risk depending on family history of cancer in two prospective cohorts. Int J Cancer. 2020; 146:1198-1207. (IF 5.14, citations 0)
https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.32397
19. Ramne S, Gray N, Hellstrand S, Brunkwall L, Enhörning S, Nilsson PM, Engström G, Orho-Melander M, Ericson U, Kuhnle GGC, Sonestedt E. Comparing Self-Reported Sugar Intake With the Sucrose and Fructose Biomarker From Overnight Urine Samples in Relation to Cardiometabolic Risk Factors. Front Nutr. 2020; 7:62. (IF 3.36, citations 1)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218081/
20. Smith E, Ottosson F, Hellstrand S, Ericson U, Orho-Melander M, Fernandez C, Melander O. Ergothioneine is associated with reduced mortality and decreased risk of cardiovascular disease. Heart. 2020; 106:691-697. (IF 5.42, citations 5)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229907/
| Acronym | BIOMENDELIAN |
|---|---|
| Status | Finished |
| Effective start/end date | 2015/09/01 → 2020/08/30 |