The mind's ratioHow the balance between ω-6 and ω-3 fatty acids affects the risk of late-life dementia
The mind's ratio
How the balance between ω-6 and ω-3 fatty acids affects the risk of late-life dementia
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DissertationDate of Exam
25.11.2021Date of Publication
03.02.2022Advisor
Ramirez, AlfredoCo-Referee
Nöthen, Markus M.Metadata
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Abstract
Dementia health care costs are rapidly rising due to the increasing number of people with dementia worldwide that is expected to increase to 66 million by 2030 and 115 million by 2050 (Prince et al., 2013). Intensive research has clearly shown that dementia is caused by multiple factors, making it challenging to provide therapy. Understanding the complex interactions between genetic, lifestyle and environmental factors is crucial to developing efficient preventive measures and recommendations that help to significantly reduce the risk of dementia. The disease’s multi-causal pathogenesis and interactions presents an incredible challenge particularly at the level of an individual person (Eid et al., 2019). Furthermore, the multi-causal factors that play a role in aetiology and progression of the disease make it more likely that dementia/AD may be prevented rather than cured (Scheltens et al., 2016). Diet has been associated with many non-communicable diseases that are shown to increase the risk of dementia (Simopoulos, 2006; Micha et al., 2014; de Bruijn et al., 2015; Scarmeas et al., 2018; Livingston et al., 2020), and thus plays an important role in the prevention of lifestyle and chronic diseases. Scientific evidence points to an important role of nutrition and ω‑3 FAs in particular on human health and cognition, while interventional studies also show inconclusive results (Cederholm, 2017; Calder, 2018; Power et al., 2019).
The current diet in North America and parts of Europe has changed dramatically in the type and amount of fat and micronutrients consumed during the past 150-200 years. As a result, the ratio of ω‑6 to ω‑3 PUFAs has risen to 10:1 and higher, compared to a hunter-gatherer diet ratio that has been estimated to be between 1:1 and 3:1 (Simopoulos, 2003; Cordain et al., 2005). With the MWD, individuals now consume more SFAs and TFAs and less MUFAs and PUFAs, and this change in diet has culminated in a total daily energy uptake of 72.1 % based on foods that would have contributed to little or none of the energy in the typical preagricultural hominin diet (Cordain et al., 2005). The PUFA composition of phospholipids has been shown to be associated with normal growth and development, as well as chronic diseases such as coronary heart disease, hypertension, obesity, inflammatory and autoimmune diseases (Simopoulos, 2006). Since these are also risk factors for dementia, it is therefore of interest whether the ω‑6/ω‑3 ratio is associated with the risk of dementia. This has been addressed in the current work, as dietary FAs are not solely analysed individually but also in ratios between competing ω‑6 and ω‑3 FAs, as well as in a proportion of ω‑6 in PUFA (%ω‑6) index, in regard to their contribution to the risk of dementia. The analyses in this current work show that the ratios LA/ALA, ARA/EPA, and the %ω‑6 are associated with an increased risk of dementia. Of the individual FAs analysed, only EPA showed a protective effect on the risk of dementia. No interaction between the investigated FAs, the FADS genotype and the APOE ε4 status was found in the investigated sample, except for the ratio SFA/ω‑3 that possibly indicates an interaction of the APOE ε4 status and SFAs.
Additionally, recent findings on the evolution of the human FADS1/2 gene region that code for the desaturase enzymes in the metabolic pathways of ω‑6 to ω‑3 PUFAs are discussed in this current work, demonstrating how a formerly positive selection of advantageous mutations in the FADS1/2 gene region can lead to an increased risk of disease through diet and lifestyle in the modern Western world.
Finally, an outline is given for integrating FAs into an individualized risk profile and details how genetic information might be a useful tool to discriminate between responders and non-responders in nutritional studies. This additional genetic information would transform dietary recommendations and help guide the development of individualized diets. Furthermore, knowledge on personal genetic variants and individualized risk profiles based on FA levels could potentially promote behavioural changes in individuals, resulting in health improvements and prevention of chronic diseases (Simopoulos, 2010) and neurodegenerative diseases.
The current diet in North America and parts of Europe has changed dramatically in the type and amount of fat and micronutrients consumed during the past 150-200 years. As a result, the ratio of ω‑6 to ω‑3 PUFAs has risen to 10:1 and higher, compared to a hunter-gatherer diet ratio that has been estimated to be between 1:1 and 3:1 (Simopoulos, 2003; Cordain et al., 2005). With the MWD, individuals now consume more SFAs and TFAs and less MUFAs and PUFAs, and this change in diet has culminated in a total daily energy uptake of 72.1 % based on foods that would have contributed to little or none of the energy in the typical preagricultural hominin diet (Cordain et al., 2005). The PUFA composition of phospholipids has been shown to be associated with normal growth and development, as well as chronic diseases such as coronary heart disease, hypertension, obesity, inflammatory and autoimmune diseases (Simopoulos, 2006). Since these are also risk factors for dementia, it is therefore of interest whether the ω‑6/ω‑3 ratio is associated with the risk of dementia. This has been addressed in the current work, as dietary FAs are not solely analysed individually but also in ratios between competing ω‑6 and ω‑3 FAs, as well as in a proportion of ω‑6 in PUFA (%ω‑6) index, in regard to their contribution to the risk of dementia. The analyses in this current work show that the ratios LA/ALA, ARA/EPA, and the %ω‑6 are associated with an increased risk of dementia. Of the individual FAs analysed, only EPA showed a protective effect on the risk of dementia. No interaction between the investigated FAs, the FADS genotype and the APOE ε4 status was found in the investigated sample, except for the ratio SFA/ω‑3 that possibly indicates an interaction of the APOE ε4 status and SFAs.
Additionally, recent findings on the evolution of the human FADS1/2 gene region that code for the desaturase enzymes in the metabolic pathways of ω‑6 to ω‑3 PUFAs are discussed in this current work, demonstrating how a formerly positive selection of advantageous mutations in the FADS1/2 gene region can lead to an increased risk of disease through diet and lifestyle in the modern Western world.
Finally, an outline is given for integrating FAs into an individualized risk profile and details how genetic information might be a useful tool to discriminate between responders and non-responders in nutritional studies. This additional genetic information would transform dietary recommendations and help guide the development of individualized diets. Furthermore, knowledge on personal genetic variants and individualized risk profiles based on FA levels could potentially promote behavioural changes in individuals, resulting in health improvements and prevention of chronic diseases (Simopoulos, 2010) and neurodegenerative diseases.
Subjects
Alzheimer Erkrankung, Demenz, Prävention, Ernährung, Fettsäuren, Epigenetik, Methylierung, Alzheimer's disease, dementia, prevention, nutrition, fatty acids, omega-6, omega-3, APOE, FADS, epigenetics, methylation
Classification (DDC)
570 Biowissenschaften, Biologie 610 Medizin, GesundheitWagner-Thelen, Holger: The mind's ratio : How the balance between ω-6 and ω-3 fatty acids affects the risk of late-life dementia. - Bonn, 2022. - Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn.
Online-Ausgabe in bonndoc: https://nbn-resolving.org/urn:nbn:de:hbz:5-65361
Online-Ausgabe in bonndoc: https://nbn-resolving.org/urn:nbn:de:hbz:5-65361
@phdthesis{handle:20.500.11811/9596,
urn: https://nbn-resolving.org/urn:nbn:de:hbz:5-65361,
author = {{Holger Wagner-Thelen}},
title = {The mind's ratio : How the balance between ω-6 and ω-3 fatty acids affects the risk of late-life dementia},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2022,
month = feb,
note = {Dementia health care costs are rapidly rising due to the increasing number of people with dementia worldwide that is expected to increase to 66 million by 2030 and 115 million by 2050 (Prince et al., 2013). Intensive research has clearly shown that dementia is caused by multiple factors, making it challenging to provide therapy. Understanding the complex interactions between genetic, lifestyle and environmental factors is crucial to developing efficient preventive measures and recommendations that help to significantly reduce the risk of dementia. The disease’s multi-causal pathogenesis and interactions presents an incredible challenge particularly at the level of an individual person (Eid et al., 2019). Furthermore, the multi-causal factors that play a role in aetiology and progression of the disease make it more likely that dementia/AD may be prevented rather than cured (Scheltens et al., 2016). Diet has been associated with many non-communicable diseases that are shown to increase the risk of dementia (Simopoulos, 2006; Micha et al., 2014; de Bruijn et al., 2015; Scarmeas et al., 2018; Livingston et al., 2020), and thus plays an important role in the prevention of lifestyle and chronic diseases. Scientific evidence points to an important role of nutrition and ω‑3 FAs in particular on human health and cognition, while interventional studies also show inconclusive results (Cederholm, 2017; Calder, 2018; Power et al., 2019).
The current diet in North America and parts of Europe has changed dramatically in the type and amount of fat and micronutrients consumed during the past 150-200 years. As a result, the ratio of ω‑6 to ω‑3 PUFAs has risen to 10:1 and higher, compared to a hunter-gatherer diet ratio that has been estimated to be between 1:1 and 3:1 (Simopoulos, 2003; Cordain et al., 2005). With the MWD, individuals now consume more SFAs and TFAs and less MUFAs and PUFAs, and this change in diet has culminated in a total daily energy uptake of 72.1 % based on foods that would have contributed to little or none of the energy in the typical preagricultural hominin diet (Cordain et al., 2005). The PUFA composition of phospholipids has been shown to be associated with normal growth and development, as well as chronic diseases such as coronary heart disease, hypertension, obesity, inflammatory and autoimmune diseases (Simopoulos, 2006). Since these are also risk factors for dementia, it is therefore of interest whether the ω‑6/ω‑3 ratio is associated with the risk of dementia. This has been addressed in the current work, as dietary FAs are not solely analysed individually but also in ratios between competing ω‑6 and ω‑3 FAs, as well as in a proportion of ω‑6 in PUFA (%ω‑6) index, in regard to their contribution to the risk of dementia. The analyses in this current work show that the ratios LA/ALA, ARA/EPA, and the %ω‑6 are associated with an increased risk of dementia. Of the individual FAs analysed, only EPA showed a protective effect on the risk of dementia. No interaction between the investigated FAs, the FADS genotype and the APOE ε4 status was found in the investigated sample, except for the ratio SFA/ω‑3 that possibly indicates an interaction of the APOE ε4 status and SFAs.
Additionally, recent findings on the evolution of the human FADS1/2 gene region that code for the desaturase enzymes in the metabolic pathways of ω‑6 to ω‑3 PUFAs are discussed in this current work, demonstrating how a formerly positive selection of advantageous mutations in the FADS1/2 gene region can lead to an increased risk of disease through diet and lifestyle in the modern Western world.
Finally, an outline is given for integrating FAs into an individualized risk profile and details how genetic information might be a useful tool to discriminate between responders and non-responders in nutritional studies. This additional genetic information would transform dietary recommendations and help guide the development of individualized diets. Furthermore, knowledge on personal genetic variants and individualized risk profiles based on FA levels could potentially promote behavioural changes in individuals, resulting in health improvements and prevention of chronic diseases (Simopoulos, 2010) and neurodegenerative diseases.},
url = {https://hdl.handle.net/20.500.11811/9596}
}
urn: https://nbn-resolving.org/urn:nbn:de:hbz:5-65361,
author = {{Holger Wagner-Thelen}},
title = {The mind's ratio : How the balance between ω-6 and ω-3 fatty acids affects the risk of late-life dementia},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2022,
month = feb,
note = {Dementia health care costs are rapidly rising due to the increasing number of people with dementia worldwide that is expected to increase to 66 million by 2030 and 115 million by 2050 (Prince et al., 2013). Intensive research has clearly shown that dementia is caused by multiple factors, making it challenging to provide therapy. Understanding the complex interactions between genetic, lifestyle and environmental factors is crucial to developing efficient preventive measures and recommendations that help to significantly reduce the risk of dementia. The disease’s multi-causal pathogenesis and interactions presents an incredible challenge particularly at the level of an individual person (Eid et al., 2019). Furthermore, the multi-causal factors that play a role in aetiology and progression of the disease make it more likely that dementia/AD may be prevented rather than cured (Scheltens et al., 2016). Diet has been associated with many non-communicable diseases that are shown to increase the risk of dementia (Simopoulos, 2006; Micha et al., 2014; de Bruijn et al., 2015; Scarmeas et al., 2018; Livingston et al., 2020), and thus plays an important role in the prevention of lifestyle and chronic diseases. Scientific evidence points to an important role of nutrition and ω‑3 FAs in particular on human health and cognition, while interventional studies also show inconclusive results (Cederholm, 2017; Calder, 2018; Power et al., 2019).
The current diet in North America and parts of Europe has changed dramatically in the type and amount of fat and micronutrients consumed during the past 150-200 years. As a result, the ratio of ω‑6 to ω‑3 PUFAs has risen to 10:1 and higher, compared to a hunter-gatherer diet ratio that has been estimated to be between 1:1 and 3:1 (Simopoulos, 2003; Cordain et al., 2005). With the MWD, individuals now consume more SFAs and TFAs and less MUFAs and PUFAs, and this change in diet has culminated in a total daily energy uptake of 72.1 % based on foods that would have contributed to little or none of the energy in the typical preagricultural hominin diet (Cordain et al., 2005). The PUFA composition of phospholipids has been shown to be associated with normal growth and development, as well as chronic diseases such as coronary heart disease, hypertension, obesity, inflammatory and autoimmune diseases (Simopoulos, 2006). Since these are also risk factors for dementia, it is therefore of interest whether the ω‑6/ω‑3 ratio is associated with the risk of dementia. This has been addressed in the current work, as dietary FAs are not solely analysed individually but also in ratios between competing ω‑6 and ω‑3 FAs, as well as in a proportion of ω‑6 in PUFA (%ω‑6) index, in regard to their contribution to the risk of dementia. The analyses in this current work show that the ratios LA/ALA, ARA/EPA, and the %ω‑6 are associated with an increased risk of dementia. Of the individual FAs analysed, only EPA showed a protective effect on the risk of dementia. No interaction between the investigated FAs, the FADS genotype and the APOE ε4 status was found in the investigated sample, except for the ratio SFA/ω‑3 that possibly indicates an interaction of the APOE ε4 status and SFAs.
Additionally, recent findings on the evolution of the human FADS1/2 gene region that code for the desaturase enzymes in the metabolic pathways of ω‑6 to ω‑3 PUFAs are discussed in this current work, demonstrating how a formerly positive selection of advantageous mutations in the FADS1/2 gene region can lead to an increased risk of disease through diet and lifestyle in the modern Western world.
Finally, an outline is given for integrating FAs into an individualized risk profile and details how genetic information might be a useful tool to discriminate between responders and non-responders in nutritional studies. This additional genetic information would transform dietary recommendations and help guide the development of individualized diets. Furthermore, knowledge on personal genetic variants and individualized risk profiles based on FA levels could potentially promote behavioural changes in individuals, resulting in health improvements and prevention of chronic diseases (Simopoulos, 2010) and neurodegenerative diseases.},
url = {https://hdl.handle.net/20.500.11811/9596}
}
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