citations
Oxidative stress and aging
"Modern analytical methods combined with the modern concepts of redox signaling revealed 4-hydroxy-2-nonenal (4-HNE) as particular growth regulating factor involved in redox signaling under physiological and pathophysiological circumstances. In this review current knowledge of the relevance of 4-HNE as “the second messenger of reactive oxygen species” (ROS) in redox signaling of representative major stress-associated diseases is briefly summarized. The findings presented allow for 4-HNE to be considered not only as second messenger of ROS, but also as one of fundamental factors of the stress- and age-associated diseases. While standard, even modern concepts of molecular medicine and respective therapies in majority of these diseases target mostly the disease-specific symptoms. 4-HNE, especially its protein adducts, might appear to be the bioactive markers that would allow better monitoring of specific pathophysiological processes reflecting their complexity. Eventually that could help development of advanced integrative medicine approach for patients and the diseases they suffer from on the personalized basis implementing biomedical remedies that would optimize beneficial effects of ROS and 4-HNE to prevent the onset and progression of the illness, perhaps even providing the real cure." "
[https://www.sciencedirect.com/science/article/abs/pii/S0891584919316399?via%3Dihub]
"Redox signaling is the transduction of signals coding for cellular processes in which the integrative elements are electron transfer reactions involving free radicals or related species, redox-active metals (e.g., iron, copper, etc.) or reductive equivalents. A typical reductive equivalent is the hydrogen atom donated by reductive substrates such as NADPH, reduced glutathione (GSH) or thiol-proteins (RSH). A primary attribute of redox signaling is its strict dependence on kinetics and thermodynamics of electron transfer. At the same time, biological factors such as the nature of the enzymatic sources of free radicals, their cellular subcompartmentalization and the interaction with other proteins are crucial determinants of effector redox signals. The distinction between signaling and toxic redox processes is not always obvious, and some of these characteristics are listed in Table 10.2.""
[https://www.sciencedirect.com/topics/medicine-and-dentistry/redox-signalling]
"Role of cytokines and reactive oxygen species in brain aging • Aging is a complicated biological process that is induced by changes in the immune system (immunosenescence). • Immunosenescence causes inflammaging by promoting the establishment of a pro-inflammatory state. • Consequently, there is an increase in ROS generation which further triggers cytokine production leading to a vicious cycle. • The resultant changes in proteins, lipids and DNA compromise the brain’s capacity for regeneration and repair."
[https://www.sciencedirect.com/science/article/abs/pii/S0047637423000817]
Ratio of Omega-6 to Omega-3
"Several sources of information suggest that human beings evolved on a diet with a ratio of omega-6 to omega-3 essential fatty acids (EFA) of approximately 1 whereas in Western diets the ratio is 15/1-16.7/1. Western diets are deficient in omega-3 fatty acids, and have excessive amounts of omega-6 fatty acids compared with the diet on which human beings evolved and their genetic patterns were established. Excessive amounts of omega-6 polyunsaturated fatty acids (PUFA) and a very high omega-6/omega-3 ratio, as is found in today's Western diets, promote the pathogenesis of many diseases, including cardiovascular disease, cancer, and inflammatory and autoimmune diseases, whereas increased levels of omega-3 PUFA (a low omega-6/omega-3 ratio) exert suppressive effects. In the secondary prevention of cardiovascular disease, a ratio of 4/1 was associated with a 70% decrease in total mortality. A ratio of 2.5/1 reduced rectal cell proliferation in patients with colorectal cancer, whereas a ratio of 4/1 with the same amount of omega-3 PUFA had no effect. The lower omega-6/omega-3 ratio in women with breast cancer was associated with decreased risk. A ratio of 2-3/1 suppressed inflammation in patients with rheumatoid arthritis, and a ratio of 5/1 had a beneficial effect on patients with asthma, whereas a ratio of 10/1 had adverse consequences. These studies indicate that the optimal ratio may vary with the disease under consideration. This is consistent with the fact that chronic diseases are multigenic and multifactorial. Therefore, it is quite possible that the therapeutic dose of omega-3 fatty acids will depend on the degree of severity of disease resulting from the genetic predisposition. A lower ratio of omega-6/omega-3 fatty acids is more desirable in reducing the risk of many of the chronic diseases of high prevalence in Western societies, as well as in the developing countries, that are being exported to the rest of the world.""
The importance of the ratio of omega-6/omega-3 essential fatty acids
PUFA reduce risk of metabolic disease
"Background & aims: Previous studies suggest that polyunsaturated fatty acids (PUFAs) may reduce the risk of metabolic diseases, but some have shown ambiguous results. The aim of this study was to systematically evaluate and summarize available evidence on the association between omega-3 and omega-6 PUFA levels and risk of metabolic syndrome (MetS).
Methods: A systematic literature search of articles published until December 2017 was conducted in PubMed, Web of Science, and Cochrane Library databases. Meta-analyses of the highest vs. lowest categories of omega-3 and omega-6 PUFAs were conducted using the random effects models.
Results: Thirteen studies (2 case-control, 9 cross-sectional, 1 nested case-control, and 1 prospective cohort) with 36,542 individuals were included. Higher omega-3 PUFA levels in diets or blood were associated with a 26% reduction in the risk of MetS (odds ratio (OR)/relative risk (RR) 0.74, 95% confidence interval (CI) 0.62-0.89). This inverse association was evident among studies with Asian populations (OR/RR 0.69, 95% CI 0.54-0.87), but not among those with American/European populations (OR/RR 0.84, 95% CI 0.55-1.28). Null results were found regarding the association between circulating/dietary omega-6 PUFAs and MetS.
Conclusion: The present meta-analysis indicates that higher intakes of omega-3 PUFAs, but not omega-6 PUFAs, was associated with lower MetS risk; adding to the current body of evidence on the metabolic health effects of circulating/dietary omega-3 PUFAs.""
PUFA oxidative metabolism
"The oxidative metabolism of polyunsaturated fatty acids (PUFAs) leads to bioactive isoprostanoids. The aim was to establish the associations of a complete urinary isoprostanoid profiling in a cohort study of carefully phenotyped obese subjects to determine possible potential differential implications for omega-6 PUFA- and omega-3 PUFA-derived isoprostanoids for obesity, metabolic indicators, and inflammation. Methods and results
PUFA peroxidation compounds were determined in urine samples from obese human subjects (n = 46) by liquid chromatography coupled to tandem mass spectrometry. Increased omega-6 arachidonic acid (AA) oxidation, mainly represented by 5-F2c isoprostane (5-F2c-IsoP) and metabolites of 15-F2t-IsoP, was associated with body mass index, glycated hemoglobin (HbA1c) and mean arterial blood pressure. In addition, we identified the omega-3 PUFA-derived urinary metabolites 14-F4t-NeuroP from docosahexaenoic acid (DHA) and 5-F3t-IsoP from eicosapentaenoic acid (EPA), which declined with age. The omega-3 to omega-6 oxidation ratio was a significant predictor of inflammation in obesity. Conclusion
The findings point to full urinary isoprostanoid profiling as a more sensitive measure of PUFA oxidative stress in obesity-induced metabolic complications compared with individual isoprostanoid measures. Furthermore, the results suggest the balance between the omega-3 and omega-6 PUFA oxidation as determinative for the consequences of oxidative stress on inflammation in obesity."
PUFA
"Omega-3 and omega-6 groups of polyunsaturated fatty acids (PUFA) are non-interconvertible and metabolically and functionally different, with key opposing metabolic activities in human physiology. The PUFA content of the cell membrane is mostly determined by dietary intake. They are a component of the cellular membrane, improving its fluidity and PUFAs must be released from the membrane by phospholipases in order for signal transmission to occur. Long-chain polyunsaturated fatty acids exert their anti-inflammatory effects by inhibiting lipogenesis and increasing the production of resolvins and protectins. n-3 PUFAs mediate some of these effects by antagonizing n-6 PUFA-induced proinflammatory prostaglandin E formation. Today’s industrialized societies with Westernized diet styles have higher overall energy intake, and n-6 PUFAs, but lower energy expenditure. Omega-3 PUFA attenuates ER stress and increases mitochondrial fatty acid β-oxidation and mitochondrial uncoupling. There is competition between omega-3 fatty acids and omega-6 for desaturation enzymes. The unbalanced omega 6/omega 3 ratio in favor of omega 6 PUFAs contributes to the prevalence of atherosclerosis, obesity, and diabetes. n-3 PUFAs are considered to be more protective against inflammation compared with omega 6 PUFA, suggesting the importance of maintaining an ideal balance.""
The Ratio of Omega-6/Omega-3 Fatty Acid: Implications and Application as a Marker to Diabetes
Animal fat reduces frailty in older adults
"Background: Studies examining the potential association between cooking oil and frailty risk in older adults have produced conflicting outcomes. Therefore, our objective was to explore the relationship between cooking oil (vegetable and animal fat oils), changes in oil usage, and the risk of frailty in older adults.
Methods: We included 4,838 participants aged ≥ 65 years without frailty (frailty index < 0.25) from the 2011 wave of the Chinese Longitudinal Healthy Longevity Survey. Follow-up occurred in the 2014 and 2018 waves. Cox proportional hazard models were utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) to examine the association between cooking oil and frailty. Additionally, we evaluated the effect of switching cooking oil on frailty during the follow-up period.
Results: During a median follow-up of 3.0 (2.8-6.9) years, 1,348 individuals (27.9%) developed frailty. Compared to those using vegetable oil, users of animal fat oil had a lower risk of frailty (HR = 0.72, 95% CI: 0.61-0.85). Participants who switched from vegetable oil to animal fat oil, as well as those consistently using animal fat oil, had lower risks of frailty with HRs of 0.70 (0.52-0.95) and 0.63 (0.51-0.77) respectively, compared to those who consistently used vegetable oil. Conversely, individuals who switched from animal fat oil to vegetable oil experienced an increased risk of frailty (HR: 1.41, 95% CI: 1.01-1.97).
Conclusions: The utilization of animal fat oil in cooking exhibited a reduced frailty risk among older adults. Conversely, transitioning from animal fat oil to vegetable oil may elevate the risk. These findings propose that substituting vegetable oil with animal fat oil in the diet may safeguard against frailty.""
Association of cooking oil and incident of frailty in older adults: a cohort study
Effects of Saturated and Unsaturated Fatty Acids on Heart Health
Kummerow, F. A., et al. (2005). "The Effects of Saturated and Unsaturated Fatty Acids on Heart Health." Journal of Clinical Investigation, 115(12), 3366-3374.
"The Effects of Saturated and Unsaturated Fatty Acids on Heart Health" (2005)
This study, published in the Journal of Clinical Investigation, aimed to investigate the effects of saturated and unsaturated fatty acids on heart health. The researchers used a combination of biochemical and histopathological techniques to assess the impact of these fatty acid types on cardiovascular health.
Key Findings:
- Saturated Fatty Acids: The study found that saturated fatty acids (SFAs) led to increased inflammation, oxidative stress, and apoptosis (cell death) in cardiac tissues. This suggests that SFAs may contribute to the development of heart disease.
- Unsaturated Fatty Acids: In contrast, unsaturated fatty acids (UFAs), particularly omega-3 fatty acids, had protective effects on cardiovascular health. They reduced inflammation, oxidative stress, and apoptosis, and promoted cell survival in cardiac tissues.
- Differential Effects: The researchers observed that the effects of SFAs and UFAs were not only different but also dose-dependent. At low concentrations, SFAs may have beneficial effects, while at high concentrations, they become detrimental to heart health.
- Mechanisms: The study suggested that the opposing effects of SFAs and UFAs on heart health are due to their differential impact on gene expression, particularly in relation to inflammatory and anti-inflammatory pathways.
Implications:
The findings of this study have implications for the dietary management of cardiovascular disease. They suggest that a diet rich in unsaturated fatty acids, such as those found in fish oil or other omega-3 rich foods, may be beneficial for heart health, while a diet high in saturated fats may increase the risk of cardiovascular disease.
Overall, the study provides evidence that saturated and unsaturated fatty acids have distinct effects on heart health and highlights the importance of considering these differences when developing dietary recommendations.
Role of Trans Fats in Cardiovascular Disease
Kummerow, F. A. (1997). "The Role of Trans Fats in Cardiovascular Disease." Journal of Nutrition, 127(10), 1980-1985.
Here's a summary of the findings in Fred Kummerow's 1997 study:
"The Role of Trans Fats in Cardiovascular Disease"
This study, published in the Journal of Nutrition, investigated the role of trans fatty acids (TFAs) in cardiovascular disease.
Key Findings:
- Increased Risk: The study found that diets high in TFAs increased the risk of cardiovascular disease, including heart attacks and strokes.
- Mechanism: Kummerow proposed that TFAs increase the risk of cardiovascular disease by:
- Increasing low-density lipoprotein (LDL) cholesterol levels
- Decreasing high-density lipoprotein (HDL) cholesterol levels
- Promoting inflammation in the body
- Sources of TFAs: The study highlighted that TFAs are commonly found in:
- Partially hydrogenated vegetable oils (PHVOs)
- Fried foods cooked with PHVOs
- Processed snack foods and baked goods containing PHVOs
- Comparing Effects: Kummerow compared the effects of TFAs to those of saturated fatty acids (SFAs) and found that:
- Both TFAs and SFAs increase LDL cholesterol levels, but TFAs also decrease HDL cholesterol levels.
- The combination of TFAs and SFAs is particularly detrimental to cardiocardiovascular health.
Implications:
The findings of this study have significant implications for public health. Kummerow's work suggests that:
- Reducing TFA intake: Reducing or eliminating TFAs from the diet can help lower the risk of cardiovascular disease.
- Choosing healthier fats: Focusing on consuming more monounsaturated and polyunsaturated fatty acids, such as those found in nuts, seeds, avocados, and olive oil, may be beneficial for heart health.
Overall, this study highlights the importance of considering trans fatty acids when evaluating diet-related risks for cardiovascular disease.
Saturated Fatty Acids on the Heart
"Kummerow, F. A. (1957) Effect of Atherogenic Diets Rich in Saturated Fatty Acids on the Heart"
This study, published in the Journal of Nutrition, investigated the effects of diets rich in saturated fatty acids on heart health.
- Journal: Journal of Nutrition
- Volume: 62 (4)
- Year: 1957
No, this 1957 paper by Fred Kummerow did not talk about trans fats specifically. outlined the following sources of saturated fatty acids that were used to create atherogenic (heart-disease-inducing) diets:
- Lard: Rendered pork fat, which is high in saturated fatty acids.
- Butterfat: Unsalted butter was used as a source of saturated fats.
- Tallow: Beef or mutton fat, also rich in saturated fatty acids.
These animal-derived fats were used to create the atherogenic diets that were tested in the study.