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Effects of a Mediterranean Diet Intervention on Maternal Stress, Well-Being, and Sleep Quality throughout Gestation-The IMPACT-BCN Trial.
Casas, I, Nakaki, A, Pascal, R, Castro-Barquero, S, Youssef, L, Genero, M, Benitez, L, Larroya, M, Boutet, ML, Casu, G, et al
Nutrients. 2023;15(10)
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Stress and anxiety are frequent occurrences among pregnant women. Mental disorders can appear before pregnancy, with a changing course during pregnancy and postpartum. During pregnancy, evidence has been provided regarding the potential beneficial effects that structured dietary interventions based on a Mediterranean diet (MedDiet) can have, not only on pregnant women, but also their offspring and the pregnancy itself. The aim of this study was to evaluate the influence of a structured intervention during pregnancy based on a MedDiet on maternal stress and anxiety, mindful state, quality of life and sleep. This study is a parallel, unblinded randomised clinical trial. Participants - pregnant women at high risk for small-for-gestational-age newborns - were randomly assigned (1:1:1) to one of the three study groups: a MedDiet supplemented with extra-virgin olive oil and walnuts; a stress reduction intervention based on the Mindfulness-Based Stress Reduction (MBSR) programme; or usual care without any intervention (control group). Results show that an intervention based on MedDiet during pregnancy: - significantly improved well-being and sleep quality. - is associated with a reduction in maternal anxiety/stress, together with an increase in the cortisol-deactivating enzyme. Authors conclude that a MedDiet intervention significantly reduces maternal anxiety and stress, as well as improving well-being and sleep quality during gestation.
Abstract
Stress and anxiety are frequent occurrences among pregnant women. We aimed to evaluate the effects of a Mediterranean diet intervention during pregnancy on maternal stress, well-being, and sleep quality throughout gestation. In a randomized clinical trial, 1221 high-risk pregnant women were randomly allocated into three groups at 19-23 weeks' gestation: a Mediterranean diet intervention, a Mindfulness-Based Stress Reduction program, or usual care. All women who provided self-reported life-style questionnaires to measure their anxiety (State Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS)), well-being (WHO Five Well Being Index (WHO-5)), and sleep quality (Pittsburgh sleep quality index (PSQI)) at enrollment and at the end of the intervention (34-36 weeks) were included. In a random subgroup of 106 women, the levels of cortisol and related metabolites were also measured. At the end of the intervention (34-36 weeks), participants in the Mediterranean diet group had significantly lower perceived stress and anxiety scores (PSS mean (SE) 15.9 (0.4) vs. 17.0 (0.4), p = 0.035; STAI-anxiety mean (SE) 13.6 (0.4) vs. 15.8 (0.5), p = 0.004) and better sleep quality (PSQI mean 7.0 ± 0.2 SE vs. 7.9 ± 0.2 SE, p = 0.001) compared to usual care. As compared to usual care, women in the Mediterranean diet group also had a more significant increase in their 24 h urinary cortisone/cortisol ratio during gestation (mean 1.7 ± SE 0.1 vs. 1.3 ± SE 0.1, p < 0.001). A Mediterranean diet intervention during pregnancy is associated with a significant reduction in maternal anxiety and stress, and improvements in sleep quality throughout gestation.
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Anxiety, anhedonia and food consumption during the COVID-19 quarantine in Chile.
Landaeta-Díaz, L, González-Medina, G, Agüero, SD
Appetite. 2021;164:105259
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It has been recognised that mechanisms to cope with stress and the inability to feel pleasure can include eating foods high in sugar, carbohydrates, and fat, resulting in obesity. The current Covid-19 pandemic could be causing stress and anxiety to many individuals. This cross-sectional study aimed to determine the role of anxiety and reduced feelings of pleasure on diet and weight during the covid-19 pandemic in 1725 individuals in Chile. The results showed that anxiety levels were related to an increased consumption of sugar-sweetened drinks, fast food, and pastries. However, there was no relationship between lockdown measures due to Covid-19 and feelings of anxiety or reduced feelings of pleasure. Increased portion sizes were also related to anxiety levels. It was concluded that high levels of anxiety were related to increased consumption of unhealthy foods. This study could be used by healthcare professionals to recognise the need to recommend healthy eating habits for the wellbeing of patients who are suffering from anxiety.
Abstract
The current epidemic of COVID-19 has gained attention and highlighted the need for a better understanding of the population's mental health. Diet has been identified as an environmental determinant of mental health. In this regard, it has been suggested that the consumption of palatable foods represents a strategy to mitigate negative emotions, such as anxiety. This study aimed to evaluate the association between symptoms of anxiety and/or anhedonia to food consumption patterns during the period of COVID-19 quarantine in Chile. We conducted a cross-sectional study with non-randomized sampling via an online survey. A total of 1725 responses were collected. Each person self-answered the Beck Anxiety Inventory, Snaith-Hamilton Pleasure Scale for anhedonia, the Food Intake Questionnaire, and questions regarding type and duration of lockdown, as well as body weight and food serving variation. Significant correlations were observed between fried food consumption and self-reported body weight. The subjects who consumed fried food three times a week, had higher weight (63.5%) (χ2 = 48.5 and p < 0.001). Those who ate one and two or more pastries on a week had 1.41 and 1.49, respectively higher odds of reporting increased body weight. We found a relationship anxiety level and sugar-sweetened beverages level (χ2 = 25.5; p 0.013), fast food intake (χ2 = 63.4; p < 0.001), and pastry consumption (χ2 = 37.7; p < 0.001). In conclusion, it is important to monitor the evolution of these findings since they could represent a risk of increased health problems in the future post-lockdown period.
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The Impact of Nutrients on Mental Health and Well-Being: Insights From the Literature.
Muscaritoli, M
Frontiers in nutrition. 2021;8:656290
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Diet, mental health, and well-being are linked through several biological pathways. In addition to a healthy diet, nutrient supplements may be of benefit due to their ability to influence these pathways. This review aimed to outline the relationship between specific nutrients and their beneficial effect on mental health. The review outlined the various benefits of polyunsaturated fats, vitamin E, magnesium and folic acid on stress, anxiety, sleep disorders, mild cognitive impairment, depression, bipolar disorders, and obsessive-compulsive disorder. With regards to stress, it was outlined that insufficient vitamins, excessive fat and nutritional imbalance can be contributory. Human research exists to support the benefits of magnesium and polyunsaturated fat for stress and these plus vitamin E for anxiety, however it appears that evidence is lacking for vitamin E and stress and the authors did not comment on folic acid for either condition. Extensive research exists for the use of polyunsaturated fats in mild cognitive impairment, and it was stated that high doses for long periods of time may be needed to show any benefits. The use of vitamin E in cognitive impairment is controversial and more studies may be needed. The authors did not comment on magnesium or folic acid supplementation. It was concluded that an unhealthy diet and lifestyle may be associated with poor mental health and well-being and the importance of a balanced, varied diet for normal brain function. This study could be used by healthcare professionals to understand the importance of recommending a healthy diet for mental well-being in individuals who are suffering from mental health disorders.
Abstract
A good nutritional status is important for maintaining normal body function and preventing or mitigating the dysfunction induced by internal or external factors. Nutritional deficiencies often result in impaired function, and, conversely, intakes at recommended levels can resume or further enhance body functions. An increasing number of studies are revealing that diet and nutrition are critical not only for physiology and body composition, but also have significant effects on mood and mental well-being. In particular, Western dietary habits have been the object of several research studies focusing on the relationship between nutrition and mental health. This review aims to summarize the current knowledge about the relationship between the intake of specific micro- and macronutrients, including eicosapentaenoic acid, docosahexaenoic acid, alpha-tocopherol, magnesium and folic acid, and mental health, with particular reference to their beneficial effect on stress, sleep disorders, anxiety, mild cognitive impairment, as well as on neuropsychiatric disorders, all significantly affecting the quality of life of an increasing number of people. Overall data support a positive role for the nutrients mentioned above in the preservation of normal brain function and mental well-being, also through the control of neuroinflammation, and encourage their integration in a well-balanced and varied diet, accompanied by a healthy lifestyle. This strategy is of particular importance when considering the global human aging and that the brain suffers significantly from the life-long impact of stress factors.
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Associations of Dietary Intake on Biological Markers of Inflammation in Children and Adolescents: A Systematic Review.
Bujtor, M, Turner, AI, Torres, SJ, Esteban-Gonzalo, L, Pariante, CM, Borsini, A
Nutrients. 2021;13(2)
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Inflammation is the normal physiological response to injury in the body and is designed to protect the host. However, in children and adolescents, chronic low-grade inflammation has been linked to a wide range of conditions. Certain markers in the blood can be measured and used to determine levels of inflammation in the body. This review of 53 studies provides the first evidence for the association between dietary intake and biological markers of inflammation in children and adolescents. Results show that adhering to a healthy way of eating such as the Mediterranean diet, are associated with decreased levels of pro-inflammatory biomarkers. The Western Dietary pattern, as well as intake of ultra-processed foods is associated with higher levels of the same pro-inflammatory markers. A good quality diet, high in fruit and vegetables, wholegrains, fibre and healthy fats ameliorates low-grade inflammation, and therefore represents a potential therapeutic approach. It is also an important element for disease prevention in both children and adolescents.
Abstract
BACKGROUND In children and adolescents, chronic low-grade inflammation has been implicated in the pathogenesis of co- and multi-morbid conditions to mental health disorders. Diet quality is a potential mechanism of action that can exacerbate or ameliorate low-grade inflammation; however, the exact way dietary intake can regulate the immune response in children and adolescents is still to be fully understood. METHODS Studies that measured dietary intake (patterns of diet, indices, food groups, nutrients) and any inflammatory biomarkers in children and adolescents aged 2 to19 years and published until November 2020 were included in this systematic review, and were selected in line with PRISMA guidelines through the following databases: Academic Search Complete, CINAHL, Global Health, Medline COMPLETE and Web of Science-Core Collection. A total of 53 articles were identified. RESULTS Results show that adequate adherence to healthful dietary patterns such as the Mediterranean diet, or food groups such as vegetables and fruit, or macro/micro nutrients such as fibre or vitamin C and E, are associated with decreased levels of pro-inflammatory biomarkers, mainly c-reactive protein (CRP), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α), whereas adherence to a Western dietary pattern, as well as intake of food groups such as added sugars, macro-nutrients such as saturated fatty acids or ultra-processed foods, is associated with higher levels of the same pro-inflammatory biomarkers. CONCLUSIONS This is the first systematic review examining dietary intake and biological markers of inflammation in both children and adolescents. A good quality diet, high in vegetable and fruit intake, wholegrains, fibre and healthy fats ameliorates low-grade inflammation, and therefore represents a promising therapeutic approach, as well as an important element for disease prevention in both children and adolescents.
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Comparing eating behaviours, and symptoms of depression and anxiety between Spain and Greece during the COVID-19 outbreak: Cross-sectional analysis of two different confinement strategies.
Papandreou, C, Arija, V, Aretouli, E, Tsilidis, KK, Bulló, M
European eating disorders review : the journal of the Eating Disorders Association. 2020;28(6):836-846
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Stress and mental health problems which may be induced by restrictions imposed during the Covid-19 pandemic can lead to unhealthy eating habits. Restrictions have varied amongst countries and this cross-sectional analysis aimed to compare eating behaviours and symptoms of stress experienced by 1841 individuals in countries with differing lockdown measures. The results showed that individuals in the country with higher lockdown measures showed lower restraint in eating, they were more likely to overeat if they saw or smelt food and reported increased anxiety. However, they did not display depression or overeating when experiencing negative feelings. It was concluded that both countries had a high frequency of depression and anxiety. Higher restrictions were associated with greater anxiety, lower restraint and overeating when confronted with food. This paper could be used by healthcare professionals to recognise the need to include dietary advice when dealing with patients who are reporting anxiety during the current Covid-19 pandemic.
Abstract
OBJECTIVE We compared eating behaviours, and depressive and anxiety symptoms in two countries with different confinement strictness strategies and different levels of COVID-19 pandemic. METHOD A web-based cross-sectional survey was administered during and shortly after the COVID-19 related lockdown in Spain and Greece. Multivariable linear regression analyses were performed to identify country differences associated with eating behaviour, and symptoms of depression and anxiety. RESULTS This study included 1,002 responders in Spain and 839 in Greece. The mean ± SD of restraint, emotional and external eating was 2.5 ± 0.79, 2.1 ± 0.81 and 2.6 ± 0.65 in Spain, whereas 2.7 ± 0.85, 2.3 ± 0.99 and 2.9 ± 0.74 in Greece. Spanish participants had lower average scores of restraint and external eating compared to Greek participants (p < .001), but no difference was seen for emotional eating. In Spain, 13.6%, and 12.3% of the survey respondents reported moderate to severe depressive and anxiety symptoms, respectively, whereas in Greece the respective values were 18.8 and 13.2%. After adjusting for several risk factors, a higher prevalence of anxiety symptoms was observed in Spain compared to Greece (p = .001), but no difference was seen for depressive symptoms. CONCLUSIONS This study demonstrated high scores of inappropriate eating behaviours and a high frequency of depressive and anxiety symptoms in two Mediterranean countries during the COVID-19 outbreak. Our findings revealed that compared to Greek participants, Spanish participants, that faced more severe COVID-19 pandemic and stricter lockdown measures, were associated with lower restraint and external eating and increased anxiety symptoms, but not with depressive symptoms or emotional eating.
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The Impact of Coconut Oil and Epigallocatechin Gallate on the Levels of IL-6, Anxiety and Disability in Multiple Sclerosis Patients.
Platero, JL, Cuerda-Ballester, M, Ibáñez, V, Sancho, D, Lopez-Rodríguez, MM, Drehmer, E, Ortí, JER
Nutrients. 2020;12(2)
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Multiple Sclerosis (MS) is associated with high levels of inflammation, especially the inflammatory molecule interleukin 6 (IL-6). Anxiety has been reported to be linked to inflammation and IL-6. Epigallocatechin gallate (EGCG) is a naturally occurring chemical, which has anti-inflammatory properties and has been related to improvements in anxiety. This pilot study of 51 individuals with MS aimed to assess the impact of EGCG and coconut oil on IL-6 and anxiety over 4 months. The results showed that individuals receiving EGCG and coconut oil had decreased IL-6 and anxiety. However, the individuals who did not also showed decreased IL-6 but not anxiety. It was concluded that anxiety was decreased in individuals with MS when taking EGCG and coconut oil, but this does not appear to be as a direct result of decreased IL-6 levels. It may be due to the Mediterranean diet all participants were asked to follow during the intervention. This study could be used by healthcare professionals to understand the relationship between IL-6 and anxiety in patients with MS.
Abstract
BACKGROUND Due to the inflammatory nature of multiple sclerosis (MS), interleukin 6 (IL-6) is high in blood levels, and it also increases the levels of anxiety related to functional disability. Epigallocatechin gallate (EGCG) decreases IL-6, which could be enhanced by the anti-inflammatory effect of high ketone bodies after administering coconut oil (both of which are an anxiolytic). Therefore, the aim of this study was to assess the impact of coconut oil and EGCG on the levels of IL-6, anxiety and functional disability in patients with MS. METHODS A pilot study was conducted for four months with 51 MS patients who were randomly divided into an intervention group and a control group. The intervention group received 800 mg of EGCG and 60 mL of coconut oil, and the control group was prescribed a placebo. Both groups followed the same isocaloric Mediterranean diet. State and trait anxiety were determined before and after the study by means of the State-Trait Anxiety Inventory (STAI). In addition, IL-6 in serum was measured using the ELISA technique and functional capacity was determined with the Expanded Disability Status Scale (EDSS) and the body mass index (BMI). RESULTS State anxiety and functional capacity decreased in the intervention group and IL-6 decreased in both groups. CONCLUSIONS EGCG and coconut oil improve state anxiety and functional capacity. In addition, a decrease in IL-6 is observed in patients with MS, possibly due to the antioxidant capacity of the Mediterranean diet and its impact on improving BMI.
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Dietary Diversity Was Positively Associated with Psychological Resilience among Elders: A Population-Based Study.
Yin, Z, Brasher, MS, Kraus, VB, Lv, Y, Shi, X, Zeng, Y
Nutrients. 2019;11(3)
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There's a growing interest by researchers in the relationship between the diversity of people's diets and their health, including their psychological resilience. This study looked at the associations between dietary diversity (DD) and psychological resilience in 8571 elderly individuals in China. Frequency and variety of food groups was collected in order to produce an average (mean) DD score. The psychological resilience of participants was assessed using a validated research tool known as "simplified resilience score" (SRS). The statistical analysis of the data collected showed that those elders with the poorest psychological resilience scores were also eating the least diverse diets. Based on separate analyses by age group, the association of a low SRS with poor DD was more prominent in the younger elderly than the oldest old. Compared with younger participants with good DD, the risk of a low SRS was greater for younger participants with poor DD, the oldest old with good DD, and the oldest old with poor DD, with OR respectively. The greatest contribution to DD was from a high consumption of vegetables, fruits, and nuts. Our study suggested that poor DD was associated with a low psychological resilience among the Chinese elderly, especially the younger elderly. These findings suggest that eating a diet rich in a variety of vegetables, fruits, and nuts might promote psychological resilience.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Dietary polyphenols abundant in fruits, vegetables and nuts have been associated with improved psychological resilience.
- Healthcare practitioners working on the dietary diversity of their clients should focus attention on these phenolic-rich foods in the interests of psychological resilience.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
This is a population-based study involving 8571 community-based elderly individuals, where dietary diversity (DD) was assessed by means of food frequency questionnaires, and correlated with psychological resilience, assessed by a validated simplified resilience score (SRS). Low DD has been previously correlated with a high level of oxidative stress mediating oxidative damage to mitochondria and lipids in neuronal circuits, as seen in affective (anxiety, depression) and neurodegenerative conditions (Alzheimer's and Parkinson's Diseases). Conversely, dietary polyphenols, a group of phenolic compounds abundant in fruits, vegetables, and other plant sources, have been associated with improved psychological resilience.
Clinical practice applications:
The greatest contribution to dietary diversity from the totality of food groups was from a high consumption of vegetables, fruits, and nuts. This can help nutrition practitioners inform their clinical decisions when supporting individuals wanting to improve the diversity of their diet.
Considerations for future research:
Future work is necessary to further assess these findings in longitudinal studies and clinical trials, and to ascertain what the mechanisms of action are in this process. It would be particularly interesting to find out whether the gut microbiota and its communication with the brain via the gut-brain axis is part of the process.
Abstract
The association between dietary diversity (DD) and psychological resilience among older people is an underdeveloped area of research. This cross-sectional study explored the associations of DD with psychological resilience among 8571 community-based elderly individuals. The intake frequencies of food groups were collected, and dietary diversity was assessed based on the mean DD score. Psychological resilience was assessed using a simplified resilience score (SRS). Data were analyzed using multiple linear regression and logistic regression models. Poor DD was significantly associated with psychological resilience, with a β (95% CI) of -0.94 (-1.07, -0.81) for the SRS (p < 0.01) and an odds ratio (95% CI) of 1.83 (1.66, 2.01) for low SRS status. The interaction effects of age with DD were observed for the SRS (p < 0.001) and low SRS status (p < 0.001). Based on separate analyses by age group, the association of a low SRS with poor DD was more prominent in the younger elderly than the oldest old, with OR (95% CI) 2.32 (1.96, 2.74) and 1.61 (1.43, 1.82), respectively. Compared with younger participants with good DD, the risk of a low SRS was greater for younger participants with poor DD, the oldest old with good DD, and the oldest old with poor DD, with OR (95% CI) 2.39 (2.02, 2.81), 1.28 (1.09, 1.51), and 2.03 (1.72, 2.39), respectively. The greatest contribution to DD was from a high consumption of vegetables, fruits, and nuts. Our study suggested that poor DD was associated with a low psychological resilience among the Chinese elderly, especially the younger elderly. These findings suggest that augmentation of DD might promote psychological resilience.
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Gut dysbiosis: a potential link between increased cancer risk in ageing and inflammaging.
Biragyn, A, Ferrucci, L
The Lancet. Oncology. 2018;19(6):e295-e304
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This study looks at the important role our gut bacterial and commensal microbes play in supporting immunity and potentially reducing the risk of cancer from aging. Cancer risk increases as we age and is one of the main causes of reduced life expectancy. Our gut microbiome changes continually in response to diet, lifestyle, infection, and activation of immune responses. Gut dysbiosis is characterised by a shift towards proinflammatory commensals and a reduction of beneficial microbes, which can cause impairment and leakiness of the intestinal barrier. This is thought to trigger inflammaging or rather aging in a state of continual inflammation, where the immune system is in a heightened state of activation, and the body essentially creates an environment conducive to cancer. The gut is populated by trillions of species of bacteria which work together with our immune cells. As we age the diversity and density of these beneficial bacteria reduce. Therapies which support the balance of our commensal bacteria may prove effective at reducing rates of cancer in the elderly.
Abstract
Cancer incidence substantially increases with ageing in both men and women, although the reason for this increase is unknown. In this Series paper, we propose that age-associated changes in gut commensal microbes, otherwise known as the microbiota, facilitate cancer development and growth by compromising immune fitness. Ageing is associated with a reduction in the beneficial commensal microbes, which control the expansion of pathogenic commensals and maintain the integrity of the intestinal barrier through the production of mucus and lipid metabolites, such as short-chain fatty acids. Expansion of gut dysbiosis and leakage of microbial products contributes to the chronic proinflammatory state (inflammaging), which negatively affects the immune system and impairs the removal of mutant and senescent cells, thereby enabling tumour outgrowth. Studies in animal models and the importance of commensals in cancer immunotherapy suggest that this status can be reversible. Thus, interventions that alter the composition of the gut microbiota might reduce inflammaging and rejuvenate immune functions to provide anticancer benefits in frail elderly people.
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Locus of control and obesity.
Neymotin, F, Nemzer, LR
Frontiers in endocrinology. 2014;5:159
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Obesity is a multifactorial disease, which makes it a complicated issue to address. In particular psychology and a concept know as locus of control plays a huge role. Locus of control refers to an individual’s ability to acknowledge that their environment and choices are under their control. However, whether this is a cause of obesity or mutually occurring is unclear. This review of 49 papers aimed to determine the relationship between obesity and locus of control. The authors discussed that the majority of literature agrees on a correlation between locus of control and obesity, however it is not straight forward as there is no set definition for locus of control. Whether locus of control causes obesity or obesity causes locus of control was also difficult to determine, but it was stated that locus of control is difficult to change. The mechanisms behind causation were discussed and stress hormones and hormones which make you feel full or hungry were implicated. It was concluded that there is a correlation between locus of control and obesity, however which one is causal, still needs more research. This paper could be used by healthcare practitioners to understand the important role that psychology plays in the development of obesity.
Abstract
In the developed world, the hazards associated with obesity have largely outstripped the risk of starvation. Obesity remains a difficult public health issue to address, due in large part to the many disciplines involved. A full understanding requires knowledge in the fields of genetics, endocrinology, psychology, sociology, economics, and public policy - among others. In this short review, which serves as an introduction to the Frontiers in Endocrinology research topic, we address one cross-disciplinary relationship: the interaction between the hunger/satiation neural circuitry, an individual's perceived locus of control, and the risk for obesity. Mammals have evolved a complex system for modulating energy intake. Overlaid on this, in humans, there exists a wide variation in "perceived locus of control" - that is, the extent to which an individual believes to be in charge of the events that affect them. Whether one has primarily an internal or external locus of control itself affects, and is affected by, external and physiological factors and has been correlated with the risk for obesity. Thus, the path from hunger and satiation to an individual's actual behavior may often be moderated by psychological factors, included among which is locus of control.
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Reversal of cognitive decline: a novel therapeutic program.
Bredesen, DE
Aging. 2014;6(9):707-17
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Alzheimer’s Disease (AD) is estimated to affect 30 million individuals globally, with projections as high as 150 million by 2050 if no effective treatment is found. This report describes a personalised, multi-modal, therapeutic programme used with 10 individuals with various degrees of cognitive decline. The goal was to optimise metabolic parameters and lifestyle factors and was personalised based on laboratory test results. 9 out of 10 of the case study patients experienced improvement in cognitive abilities, beginning within 3-6 months of starting the programme. These effects were sustained at 2.5 year follow up. The 1 patient who did not benefit had advanced AD, in comparison to the other patients with subjective or mild cognitive decline. The authors call for a more extensive trial of the therapeutic programme.
Abstract
This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer's disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3-6 months, with the one failure being a patient with very late stage AD. Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance. Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement. These results suggest that a larger, more extensive trial of this therapeutic program is warranted. The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes. Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system.