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Do Dietary Supplements Affect Inflammation, Oxidative Stress, and Antioxidant Status in Adults with Hypothyroidism or Hashimoto's Disease?-A Systematic Review of Controlled Trials.
Kubiak, K, Szmidt, MK, Kaluza, J, Zylka, A, Sicinska, E
Antioxidants (Basel, Switzerland). 2023;12(10)
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A deficiency of the thyroid hormone causes hypothyroidism (HT), whereas Autoimmune thyroiditis (AIT) is mainly an organ-specific autoimmune condition. Both HT and AIT are characterised by low-grade inflammation and inflammation in the thyroid gland. Dietary supplements may offer health benefits; however, previous research findings are inconclusive. This systematic review evaluated twenty-two controlled studies to understand the effectiveness of dietary supplements in reducing inflammation and oxidative stress and improving antioxidant and thyroid parameters in patients with HT or AIT. The efficacy of dietary supplements in improving thyroid health and reducing inflammation and oxidative stress was inconclusive due to the low quality of the included studies and the limited number of available studies. Selenium supplements might be beneficial in improving thyroid parameters and inflammation in patients with HT or AIT. Even though the therapeutic benefits of dietary supplements in treating thyroid disease were inconclusive, healthcare professionals can use them to address the common nutritional deficiencies in people with HT and AIT. Further, large, long-term, robust studies are required to assess the therapeutic utility of different dietary supplements in promoting the health of the thyroid gland.
Abstract
This systematic review aims to summarise the results of controlled trials on dietary supplements (DS) usage and inflammation, oxidative stress, antioxidant status, and thyroid parameter improvement in hypothyroidism (HT)/Hashimoto's thyroiditis (AIT) patients. The study protocol was registered with PROSPERO (no. CRD42022365149). A comprehensive search of the PubMed, Scopus, and Web of Science databases resulted in the identification of nineteen randomised controlled trials and three non-randomised studies for the review; three studies examined the effect of supplementation with vitamin D, twelve studies-with selenium, and seven studies-with other DS. Based on very limited evidence, the lack of influence of vitamin D supplementation on inflammatory parameters was found, while no studies have examined oxidative stress and antioxidant status parameters, and only one provided results for a single thyroid parameter after an intervention. Some evidence was found proving that selenium supplementation may decrease inflammation and improve thyroid parameters, but reaching a conclusion about its influence on oxidative stress and antioxidant status is not possible because of the insufficient number of studies. Additionally, due to examining other DS (e.g., multicomponent, Nigella sativa, and genistein) only in single studies, conclusions cannot be drawn. Further long-term, high-quality randomised controlled trials are necessary to better understand the influence of DS on inflammation, oxidative stress, and antioxidant status, as well as their potential to improve thyroid gland function in HT/AIT patients.
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Fasting, Hormones, and Men’s Sexual Health
As the pioneer and global leader of Functional Medicine, the Institute of Functional Medicine leads and catalyses the efforts of a large and expanding Functional Medicine ecosystem, including providers, educators, payers, industry leaders, regulators, and influencers.
2023
Abstract
IFM practitioner Mark Holthouse discusses male hormone dysregulation, specifically low testosterone and the impact that this might have on men’s sexual health and function. They explore lifestyle factors such as stress, sleep and body composition on testosterone levels; the metabolic pathways that might lower testosterone such as intestinal permeability, insulin resistance and aromatase upregulation, and how to mitigate this via intermittent fasting, phytonutrient intake and strength training to name a few.
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Lactobacillus rhamnosus CNCM I-3690 decreases subjective academic stress in healthy adults: a randomized placebo-controlled trial.
Wauters, L, Van Oudenhove, L, Accarie, A, Geboers, K, Geysen, H, Toth, J, Luypaerts, A, Verbeke, K, Smokvina, T, Raes, J, et al
Gut microbes. 2022;14(1):2031695
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Previous research has shown a bidirectional relationship between the gut and psychological stress, which could be mediated by intestinal permeability followed by an immune and inflammatory response. However, the exact mechanisms of this relationship are yet to be elucidated. This randomised, double-blind, placebo-controlled trial evaluated the beneficial effects of Lactobacillus rhamnosus CNCM I-3690 on intestinal permeability and stress markers during a public speech in healthy students. Participants consumed either milk containing Lactobacillus rhamnosus CNCM I-3690 or acidified milk twice daily for four weeks to assess subjective and objective stress markers and markers of intestinal permeability. Lactobacillus rhamnosus CNCM I-3690 reduced the stress-induced hyperpermeability to mannitol and subjective stress markers (State-Trait Anxiety Inventory/ STAI). A subgroup of healthy students with stress-induced cortisol >P90 of baseline showed a reduction in perceived stress score following Lactobacillus rhamnosus CNCM I-3690 intervention. To evaluate the additional effects of Lactobacillus rhamnosus CNCM I-3690 on stress and gut health, further robust studies are needed. Healthcare professionals can use the findings of this study to understand the anxiolytic effects of Lactobacillus rhamnosus CNCM I-3690.
Abstract
Psychological stress negatively affects the intestinal barrier function in animals and humans. We aimed to study the effect of Lactobacillus rhamnosus CNCM I-3690 on intestinal permeability and stress-markers during public speech. Healthy students were randomized to L. rhamnosus-containing (test) or acidified (placebo) milk consumed twice daily for 4 weeks, with 46 subjects per treatment group. Small intestinal permeability was quantified by a 2 h urinary lactulose-mannitol ratio (LMR, primary outcome), fractional excretion of lactulose (FEL) and mannitol (FEM). Salivary cortisol, State-Trait Anxiety Inventory (STAI) and Perceived Stress scores (PSS) were collected. No between-treatment differences were found for LMR (p = .71), FEL or FEM. Within-treatment analyses showed similar LMR and FEL but a stress-induced increase of FEM with the placebo (p < .05) but not test product. Despite a similar increase in salivary cortisol, the stress-induced increase in STAI was significantly lower with the test product vs. placebo (p = .01). Moreover, a stress-preventative effect of the probiotic was found for PSS and more pronounced in subjects with high stress-induced cortisol (p = .01). While increased FEM was mediated by salivary cortisol levels, the effect of the test product on subjective stress was not mediated by changes in FEM. No serious adverse events occurred. In conclusion, we demonstrated that L. rhamnosus CNCM I-3690 prevented stress-induced hyperpermeability to mannitol. Subjective but not objective stress-markers were reduced with L. rhamnosus vs. placebo, suggesting anxiolytic effects, which were independent of barrier stabilization and attractive for the reduction of stress in both health and disease. Clinicaltrials.gov, number NCT03408691.
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The impact of diabetes mellitus type 1 on male fertility: Systematic review and meta-analysis.
Facondo, P, Di Lodovico, E, Delbarba, A, Anelli, V, Pezzaioli, LC, Filippini, E, Cappelli, C, Corona, G, Ferlin, A
Andrology. 2022;10(3):426-440
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The relationship between type 2 diabetes mellitus and male hypogonadism is well known, whereas the impact of type 1 diabetes mellitus (DM1) on male fertility and testis functions has been less studied. The aim of this study was to systematically review and discuss the available evidence evaluating paternity rate, male gonadal axis, and sperm parameters in men with DM1. This study is a systematic review and meta-analysis of fourteen studies. Results show: - reduced fertility potential in patients with DM1, as they have a lower number of children compared with unaffected population. In fact, the rate of children is statistically significantly lower among men who had been diagnosed with DM1 at an earlier age, according to a longer duration of the disease. - that men with DM1, compared with controls, have significantly lower normal sperm morphology, progressive motility and a trend toward a reduced semen volume, without difference in total sperm count and concentration. Authors conclude that DM1 might impair reproductive health at different levels, including functional sperm alterations definitively leading to reduced fertility rate in these patients.
Abstract
BACKGROUND Some evidence suggests that diabetes mellitus type 1 (DM1) could affect male fertility, gonadal axis, semen parameters, and spermatogenesis because of effects of hyperglycemia and insulin deficiency. Anyhow, the exact impact of DM1 on male fertility is unclear. OBJECTIVES To review the studies evaluating paternity rate, male gonadal axis, and semen parameters in men with DM1. MATERIALS AND METHODS A review of relevant literature from January 1980 to December 2020 was performed. Only studies published in English reporting data on fatherhood (rate of children by natural fertility), hormonal and seminal parameters were included. Out of 14 retrieved articles, the eight studies evaluating semen parameters were meta-analyzed. RESULTS The rate of children (four studies) was lower than controls among men affected by DM1, especially in men with a longer duration of disease. The data of gonadal hormonal profile in DM1 men (six studies) are very heterogeneous and a neutral effect of DM1 or a condition of subclinical hypogonadism could not be concluded. Meta-analysis showed that men with DM1 (n = 380), compared with controls (n = 434), have significantly lower normal sperm morphology [-0.36% (-0.66; -0.06), p < 0.05, six studies] and sperm progressive motility [33.62% (-39.13; -28.11), p < 0.001, two studies] and a trend toward a lower seminal volume [-0.51 (-1.03; 0.02), p = 0.06, eight studies], without difference in total sperm count and concentration. Data on scrotal ultrasound and sperm DNA fragmentation are too few. No study evaluated other factors of male infertility, such as transrectal ultrasound, semen infections, sperm auto-antibodies, and retrograde ejaculation. DISCUSSION DM1 might impair male fertility and testis functions (endocrine, spermatogenesis), but definition of its actual impact needs further studies. CONCLUSION Men with DM1 should be evaluated with a complete hormonal, seminal, and ultrasound workup to better define their fertility potential and need for follow up of testis functions.
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Coping Strategies Influence Cardiometabolic Risk Factors in Chronic Psychological Stress: A Post Hoc Analysis of A Randomized Pilot Study.
Armborst, D, Bitterlich, N, Alteheld, B, Rösler, D, Metzner, C, Siener, R
Nutrients. 2021;14(1)
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Chronic psychological stress is increasingly recognized as a significant contributor to mental and physiological disorders in modern societies. The individual response to chronic stressors and resulting disorders depends on numerous factors. The aim of this study was to investigate the cardiometabolic risk profile in participants with ‘high’ and ‘very high’ chronic stress loads and the impact of positive and negative coping factors used. This study is a post hoc analysis of a randomised pilot study. For this analysis, baseline data were available for 62 chronic psychologically stressed participants, of whom 61 participants (43 women and 18 men) were included in the intention-to-treat (ITT) population. Results indicate that: - perceiving high chronic stress is significantly associated with the criteria of the metabolic syndrome. - on the contrary, a very high perceived chronic stress load seemed to be rather associated with mental health risk than with cardiometabolic risk. - inflammation and oxidative stress markers significantly correlated with cardiometabolic risk parameters. - stress load can be coped with in diverse ways and that the coping strategy is crucial for cardiometabolic risk. Authors conclude that long-term studies are necessary to examine further adaptations to chronic stress and to evaluate individual stress-management strategies.
Abstract
Chronic psychological stress can result in physiological and mental health risks via the activation of the hypothalamic-pituitary-adrenal (HPA) axis, sympathoadrenal activity and emotion-focused coping strategies. The impact of different stress loads on cardiometabolic risk is poorly understood. This post hoc analysis of a randomized pilot study was conducted on 61 participants (18-65 years of age) with perceived chronic stress. The Perceived Stress Questionnaire (PSQ30), Psychological Neurological Questionnaire (PNF), anthropometric, clinical and blood parameters were assessed. Subjects were assigned to 'high stress' (HS; PSQ30 score: 0.573 ± 0.057) and 'very high stress' (VHS; PSQ30 score: 0.771 ± 0.069) groups based on the PSQ30. Morning salivary cortisol and CRP were elevated in both groups. Visceral adiposity, elevated blood pressure and metabolic syndrome were significantly more frequent in the HS group vs. the VHS group. The fatty liver index (FLI) was higher (p = 0.045), while the PNF score was lower (p < 0.001) in the HS group. The HS group was comprised of more smokers (p = 0.016). Energy intake and physical activity levels were similar in both groups. Thus, high chronic stress was related to visceral adiposity, FLI, elevated blood pressure and metabolic syndrome in the HS group, while very high chronic stress was associated with psychological-neurological symptoms and a lower cardiometabolic risk in the VHS group, probably due to different coping strategies.
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What Experts Want BIPOC Women to Know About Menopause
The team behind Everyday Health is committed to providing the public with trusted, real-world, evidence-based health information from the leading healthcare providers and patient advocates, alongside personal patient perspectives and health consumer insights from those on the front lines, in real time.
2021
Abstract
This article explores the evidence around the increased length and intensity of menopausal symptoms in women of colour when compared to white women, as observed in the SWAN study (Study of Women’s Health Across the Nation). This is a thought-provoking read. It discusses the aspects of life that can let health disparities arise between different ethnic communities, and that are required to be considered by healthcare professionals when working to support individuals.
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Differential Health Effects on Inflammatory, Immunological and Stress Parameters in Professional Soccer Players and Sedentary Individuals after Consuming a Synbiotic. A Triple-Blinded, Randomized, Placebo-Controlled Pilot Study.
Quero, CD, Manonelles, P, Fernández, M, Abellán-Aynés, O, López-Plaza, D, Andreu-Caravaca, L, Hinchado, MD, Gálvez, I, Ortega, E
Nutrients. 2021;13(4)
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Synbiotic, a mixture of prebiotics and probiotics, is known to improve neurotransmitter interactions, immune, inflammatory, and stress responses by modulating the gut microbial composition. It is also believed that physical activity plays an important role in the modulation of immune function and stress response. The purpose of this triple-blinded, randomized, placebo-controlled pilot study was to evaluate the health benefits of symbiotic intervention in fourteen sedentary students and thirteen soccer players, especially in terms of improving immunophysiological and metabolic parameters. The 300mg of symbiotic intervention contained Bifidobacterium lactis CBP-001010, Lactobacillus rhamnosus CNCM I-4036, Bifidobacterium longum ES1(109 colony-forming unit), and fructooligosaccharides (200 mg) plus 1.5 mg of zinc, 8.25 µg of selenium, 0.75 µg of vitamin, and maltodextrin. Following a one-month intervention with synbiotic formulation, soccer players showed improvements in anxiety, sleep quality and stress, a slight reduction in proinflammatory cytokine IL-1β, an exercise-induced significant increase in dopamine and a slight elevation of corticotropin-releasing hormone. For confirmation of results of this pilot study and to assess more significant effects of symbiotic intervention in athletes as well as in the general population, longer-term robust studies are required. The findings of this study can help healthcare professionals understand the extensive health benefits of synbiotic intervention and its relationship to physical activity.
Abstract
The main objective of this research was to carry out an experimental study, triple-blind, on the possible immunophysiological effects of a nutritional supplement (synbiotic, Gasteel Plus®, Heel España S.A.U.), containing a mixture of probiotic strains, such as Bifidobacterium lactis CBP-001010, Lactobacillus rhamnosus CNCM I-4036, and Bifidobacterium longum ES1, as well as the prebiotic fructooligosaccharides, on both professional athletes and sedentary people. The effects on some inflammatory/immune (IL-1β, IL-10, and immunoglobulin A) and stress (epinephrine, norepinephrine, dopamine, serotonin, corticotropin-releasing hormone (CRH), Adrenocorticotropic hormone (ACTH), and cortisol) biomarkers were evaluated, determined by flow cytometer and ELISA. The effects on metabolic profile and physical activity, as well as on various parameters that could affect physical and mental health, were also evaluated via the use of accelerometry and validated questionnaires. The participants were professional soccer players in the Second Division B of the Spanish League and sedentary students of the same sex and age range. Both study groups were randomly divided into two groups: a control group-administered with placebo, and an experimental group-administered with the synbiotic. Each participant was evaluated at baseline, as well as after the intervention, which lasted one month. Only in the athlete group did the synbiotic intervention clearly improve objective physical activity and sleep quality, as well as perceived general health, stress, and anxiety levels. Furthermore, the synbiotic induced an immunophysiological bioregulatory effect, depending on the basal situation of each experimental group, particularly in the systemic levels of IL-1β (increased significantly only in the sedentary group), CRH (decreased significantly only in the sedentary group), and dopamine (increased significantly only in the athlete group). There were no significant differences between groups in the levels of immunoglobulin A or in the metabolic profile as a result of the intervention. It is concluded that synbiotic nutritional supplements can improve anxiety, stress, and sleep quality, particularly in sportspeople, which appears to be linked to an improved immuno-neuroendocrine response in which IL-1β, CRH, and dopamine are clearly involved.
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PROFAST: A Randomized Trial Assessing the Effects of Intermittent Fasting and Lacticaseibacillus rhamnosus Probiotic among People with Prediabetes.
Tay, A, Pringle, H, Penning, E, Plank, LD, Murphy, R
Nutrients. 2020;12(11)
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The prevalence of diabetes is increasing worldwide, and with it, the risk of cardiovascular disease is also increasing. Intermittent fasting has been shown to reduce weight and improve glycaemic control. Weight control and glycaemic control were also improved with probiotic Lacticaseibacillus rhamnosus HN001 supplementation. This pilot, 12-week, double-blinded, two-armed, randomized 1:1 study aimed to investigate the combined effects of intermittent fasting with daily probiotic Lacticaseibacillus rhamnosus HN001 supplementation on glycaemic management in participants with prediabetes. For two days, participants restricted their calorie intake to 600-650 kcal, followed by five days of ad libitum consumption (5:2). Intermittent fasting for 12 weeks improved glycaemic control (reduced HbA1c) and reduced body weight by 5%. The supplementation with Lacticaseibacillus rhamnosus HN001 did not significantly improve these outcomes. Probiotic supplementation significantly improved mental health and social functioning in participants. There is a need for further large, robust studies to assess the effects of intermittent fasting alone and when it is combined with different exercise forms and different prebiotic and probiotic supplements on cardiometabolic markers and mental health. The findings of this study may be useful to healthcare professionals in understanding the effects of fasting on metabolism as well as the psychological benefits of Lacticaseibacillus rhamnosus HN001 supplementation.
Abstract
Both intermittent fasting and specific probiotics have shown promise in improving glucose tolerance with a potential for synergistic effects through alterations to gut microbiota. In this randomized, double-blinded, two-arm feasibility study, we investigated whether intermittent fasting, supplemented with Lacticaseibacillus rhamnosus HN001 probiotic, reduces HbA1c in individuals with prediabetes. All participants with HbA1c 40-50 mmol/mol commenced intermittent fasting (2 days per week of calorie restriction to 600-650 kcal/day) and were randomized 1:1 to either daily probiotic (Lacticaseibacillus rhamnosus HN001) or placebo for 12 weeks. The primary outcome was a change in HbA1c. Secondary outcomes included changes in anthropometry, body composition, glucoregulatory markers, lipids, hunger hormones, liver enzymes, inflammatory markers, gut hormones, calorie and macronutrient intake, quality of life, hunger, mood and eating behavior. Of 33 participants who commenced the trial, 26 participants (mean age 52 years, body mass index (BMI) 34.7 kg/m2) completed the intervention (n = 11 placebo, n = 15 probiotic). HbA1c decreased from 43 ± 2.7 mmol/mol to 41 ± 2.3 mmol/mol, p < 0.001, with average of 5% weight loss. No significant between-group differences were seen in primary or secondary outcomes except for social functioning (p = 0.050) and mental health (p = 0.007) scores as improvements were seen in the probiotic group, but not in the placebo group. This study shows additional psychological benefits of probiotic supplementation during intermittent fasting to achieve weight loss and glycemic improvement in prediabetes.
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Cashew apple juice supplementation enhances leukocyte count by reducing oxidative stress after high-intensity exercise in trained and untrained men.
Prasertsri, P, Roengrit, T, Kanpetta, Y, Tong-Un, T, Muchimapura, S, Wattanathorn, J, Leelayuwat, N
Journal of the International Society of Sports Nutrition. 2019;16(1):31
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High-intensity aerobic training has been shown to suppress leukocyte counts in moderately fit athletes. The aim of this study to explore possible advantageous effects of cashew apple juice (CAJ) supplementation, and, if present, to identify the possible mechanisms underlying those effects. The study is a double-blind randomised cross-over design with two treatment arms: CAJ supplementation and placebo. Ten moderately (endurance) trained and untrained men were randomized to one of the two groups for four weeks, with a four-week wash out period. Results showed that CAJ supplementation for four weeks increased leukocyte (a type of blood cell) counts, while simultaneously decreasing oxidative stress, following an acute bout of high-intensity exercise in trained men. Furthermore, the CAJ supplementation increased neutrophil (a type of white blood cell) counts while simultaneously reducing oxidative stress and stress hormone concentrations in untrained men. The antioxidant effects following exercise were observed in both endurance-trained and untrained men. Authors conclude that CAJ supplementation is beneficial to men, both in resting states and in response to an acute bout of high-intensity aerobic exercise.
Abstract
BACKGROUND Cashew apple juice (CAJ) was shown to improve immunological mechanisms by regulating a balance between reactive oxygen species and antioxidant concentrations. However, no study exploring the effects of the CAJ and training status on the immune system and oxidative stress induced by exercise. Therefore, we investigated the effects of CAJ supplementation primarily on leukocyte counts and secondary on oxidative stress and cortisol changes after high-intensity exercise in trained and untrained men. METHODS Ten moderately (endurance) trained (Age = 21.5 ± 0.97 yr., VO2max = 45.6 ± 4.12 mL/kgBM/min) and ten sedentary men (Age = 20.4 ± 2.72 yr., VO2peak = 32.2 ± 7.26 mL/kgBM/min) were randomized to ingest either daily CAJ or a placebo at 3.5 mL/kgBM/day for 4 weeks, with a four-week washout period. Before and after each period, they performed 20-min, high-intensity cycling (85% VO2max), with blood samples collected immediately preceding and the following exercise. Samples were analyzed to determine leukocyte counts, malondialdehyde, 8-isoprostane, and cortisol concentrations. A repeated measures analysis of variance was used to examine the effects of supplement and training status over time with an alpha level of 0.05. RESULTS There was no interaction between supplement and training status on those variables before and after exercise. However, CAJ raised resting neutrophil counts and exercise-induced leukocyte counts in the trained group (all p < 0.05). Besides, CAJ significantly reduced plasma malondialdehyde concentrations at rest and after exercise and reduced the post-exercise plasma 8-isoprostane concentration in both groups of subjects (p < 0.05). Moreover, CAJ reduced plasma cortisol after exercise in the untrained subjects. CONCLUSIONS We suggest that 4-week CAJ supplementation can enhance exercise-induced leukocyte and resting neutrophil counts in trained men. The possible mechanism is a reduction in oxidative stress. However, the supplementation did not change the immune responses of untrained men, but it did reduce stress hormone concentrations. TRIAL REGISTRATION NUMBER TCTR20181127002 Registered 26 November 2018 "retrospectively registered".
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Metabolic Slowing and Reduced Oxidative Damage with Sustained Caloric Restriction Support the Rate of Living and Oxidative Damage Theories of Aging.
Redman, LM, Smith, SR, Burton, JH, Martin, CK, Il'yasova, D, Ravussin, E
Cell metabolism. 2018;27(4):805-815.e4
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Following a calorie-restricted diet while maintaining adequate nutrition is known to have a beneficial effect on increasing longevity and promoting healthy ageing. Oxidative stress resulting from reactive oxygen species formation in mitochondria plays a role in accelerating ageing by damaging DNA, proteins and lipids. A calorie-restriction diet can reduce oxidative stress and cause metabolic adaptations. In this ancillary study, non-obese participants were randomly assigned to either a calorie restriction group which followed 25% calorie restriction while getting adequate nutritional support through supplementation or to a control group which included ad libitum calorie intake. After 2 years of intervention, participants in the calorie restriction group achieved 15% calorie restriction, 8.7kg weight loss and a reduction in 24-hour energy expenditure and sleep energy expenditure beyond weight loss because of metabolic adaptation. Oxidative stress and thyroid axis activity were also reduced in the calorie restriction group. Further robust studies are required to evaluate the effectiveness of calorie restriction in metabolic adaptation and oxidative stress and its effects on ageing. The results of this study can be used by healthcare professionals to understand the benefits of a nutritionally adequate calorie restriction diet on adjusting metabolic processes.
Abstract
Calorie restriction (CR) is a dietary intervention with potential benefits for healthspan improvement and lifespan extension. In 53 (34 CR and 19 control) non-obese adults, we tested the hypothesis that energy expenditure (EE) and its endocrine mediators are reduced with a CR diet over 2 years. Approximately 15% CR was achieved over 2 years, resulting in an average 8.7 kg weight loss, whereas controls gained 1.8 kg. In the CR group, EE measured over 24 hr or during sleep was approximately 80-120 kcal/day lower than expected on the basis of weight loss, indicating sustained metabolic adaptation over 2 years. This metabolic adaptation was accompanied by significantly reduced thyroid axis activity and reactive oxygen species (F2-isoprostane) production. Findings from this 2-year CR trial in healthy, non-obese humans provide new evidence of persistent metabolic slowing accompanied by reduced oxidative stress, which supports the rate of living and oxidative damage theories of mammalian aging.