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We previously showed in rats that pre- and postnatal deficiencies in iron and omega-3 (n-3) fatty acids can impair bone development, with additive and potentially irreversible effects when combined. This study aimed to investigate, in female rats consuming a combined iron and n-3 fatty acid deficient (ID + n-3 FAD) diet preconception, whether supplementation with iron and docosahexaenoic/eicosapentaenoic acid (DHA/EPA), alone and in combination, can prevent bone impairments in offspring. Using a 2 × 2 factorial design, female Wistar rats consuming an ID + n-3 FAD diet preconception were randomised to receive an: 1) iron supplemented (Fe + n-3 FAD), 2) DHA/EPA supplemented (ID + DHA/EPA), 3) Fe + DHA/EPA, or 4) ID + n-3 FAD diet from gestational day 10 throughout pregnancy and lactation. Post-weaning, offspring (n = 24/group; male:female = 1:1) remained on the respective experimental diets for three weeks until postnatal day 42–45. Offspring born to female rats consuming a control diet preconception and an Fe+DHA/EPA diet throughout pregnancy and lactation served as non-deficient reference group (Control+Fe+DHA/EPA). Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry and bone strength using three-point bending tests. Only offspring in the Fe+DHA/EPA group had significantly higher spine and femur BMD, and higher femur stiffness than offspring in the ID + n-3 FAD group, and had similar spine BMD and femur stiffness as the Control + Fe + DHA/EPA group. Offspring in the Fe + DHA/EPA group further had significantly higher femur strength (ultimate load) than the other experimental groups, and a similar femur strength as the Control + Fe + DHA/EPA group. This study shows that only combined iron and DHA/EPA supplementation can prevent bone impairments in offspring of female rats consuming an iron and n-3 FA deficient diet preconception.
Diminished skeletal muscle strength and size, termed sarcopenia, contributes substantially to physical disability, falls, dependence and reduced quality of life among older people. Physical activity and nutrition are the cornerstones of sarcopenia prevention and treatment. The optimal daily protein intake required to preserve muscle mass and function among older adults is a topic of intense scientific debate. Older adults require protein intakes about 67 % higher than their younger counterparts to maximally stimulate postprandial muscle protein synthesis rates. In addition, evidence suggests a possible benefit of increasing protein intake above the population reference intake (0⋅83 g/kg/d) on lean mass and, when combined with exercise training, muscle strength. In addition to protein quantity, protein quality, the pattern of protein intake over the day and specific amino acids (i.e. leucine) represent key considerations. Long-chain n-3 PUFA (LC n-3 PUFA) supplementation has been shown to enhance muscle protein synthesis rates, increase muscle mass and function and augment adaptations to resistance training in older adults. Yet, these effects are not consistent across all studies. Emerging evidence indicates that an older person's dietary, phenotypic and behavioural characteristics may modulate the efficacy of protein and LC n-3 PUFA interventions for promoting improvements in muscle mass and function, highlighting the potential inadequacy of a ‘one-size-fits-all’ approach. The application of personalised or precision nutrition to sarcopenia represents an exciting and highly novel field of research with the potential to help resolve inconsistencies in the literature and improve the efficacy of dietary interventions for sarcopenia.
This chapter concerns neuroprotective diets, and the use of particular diets and dietary components as an intervention. The first section examines the Mediterranean diet, with its beneficial effects – as prevention and intervention – on cognitive performance, mental health and neurodegeneration. The second section explores the DASH (dietary approaches to stop hypertension) diet, which has shown promise across the same set of conditions as the Mediterranean diet, and with probably a similar set of common mechanisms (e.g., reductions in inflammation and oxidative stress, plus benefits to the cardiovascular system). The third section looks at the ketogenic diet and its variants, with its high fat to carbohydrate ratio, originally and successfully developed for paediatric epilepsy, and its more recent use in other conditions (e.g., multiple sclerosis, brain tumours). The final part of the chapter reviews single nutrients, these being either examples of polyphenols or omega-3 fatty acids, with research focussing on mental health, aging and neurodegeneration.
Coenzyme Q10 (CoQ10), a lipid involved in ATP synthesis, exhibits very limited oral absorption, and its endogenous production decreases with ageing and with the occurrence of oxidative stress. Our group previously showed that monoglycerides omega-3 (MAG-OM3) increase OM3 plasma concentrations. Since CoQ10 is liposoluble, we hypothesised that its 48 h pharmacokinetics is higher when provided with MAG-OM3 compared to CoQ10 alone (in powder form) or added to rice oil (a neutral triacylglycerol oil). A randomised triple-blind crossover study was performed with fifteen men and fifteen women consuming the three supplements providing 200 mg of CoQ10 in a random order. Blood samples were collected before (t = 0) and 1, 3, 5, 6, 7, 8, 10, 11, 24 and 48 h after the supplement intake. Plasma total CoQ10 concentrations were analysed on ultrahigh-performance liquid chromatography coupled to a tandem mass spectrometer (UPLC-MS/MS). Participants were 26⋅1 ± 4⋅8 years old. When CoQ10 was provided with rice or MAG-OM3 oils, the 48 h area under the curve (AUC 0–48 h) was approximately two times higher compared to when provided without an oil. The delta max concentration (ΔCmax) of plasma CoQ10 was, respectively, 2 (MAG-OM3) and 2⋅5 (rice oil) times higher compared to CoQ10 alone. There was a significant sex by treatment interaction (P = 0⋅0250) for the AUC 0–6 h supporting that in postprandial, men and women do not respond the same way to the different supplement. Women had a higher CoQ10 concentration 48 h after the single-dose intake compared to men. We conclude that CoQ10 supplements must be provided with lipids, and their kinetics is different between men and women.
Aspirin (acetylsalicylic acid, ASA) is inexpensive and is established in preventing cardiovascular disease (CVD) and colorectal adenomas. Omega-3 (n3) polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have also shown benefit in preventing CVD. The combination could be an effective preventative measure in patients with such diseases. ASA and n3 PUFA reduced the risk of CVD in ASA-resistant or diabetic patients. EPA- and DHA-deficient patients also benefited the most from n3 PUFA supplementation. Synergistic effects between ASA and EPA and DHA are ‘V-shaped’ such that optimal ASA efficacy is dependent on EPA and DHA concentrations in blood. In colorectal adenomas, ASA (300 mg/d) and EPA reduced adenoma burden in a location- and subtype-specific manner. Low doses of ASA (75–100 mg/d) were used in CVD prevention; however, ultra-low doses (30 mg/d) can also reduce thrombosis. EPA-to-DHA ratio is also important with regard to efficacy. DHA is more effective in reducing blood pressure and modulating systemic inflammation; however, high-dose EPA can lower CVD events in high-risk individuals. Although current literature has yet to examine ASA and DHA in preventing CVD, such combination warrants further investigation. To increase adherence to ASA and n3 PUFA supplementation, combination dosage form may be required to improve outcomes.
The diet of most adults is low in fish and, therefore, provides limited quantities of the long-chain, omega-3 fatty acids (LCn-3FAs), eicosapentaenoic and docosahexaenoic acids (EPA, DHA). Since these compounds serve important roles in the brain, we sought to determine if healthy adults with low-LCn-3FA consumption would exhibit improvements in neuropsychological performance and parallel changes in brain morphology following repletion through fish oil supplementation.
Methods
In a randomized, controlled trial, 271 mid-life adults (30–54 years of age, 118 men, 153 women) consuming ⩽300 mg/day of LCn-3FAs received 18 weeks of supplementation with fish oil capsules (1400 mg/day of EPA and DHA) or matching placebo. All participants completed a neuropsychological test battery examining four cognitive domains: psychomotor speed, executive function, learning/episodic memory, and fluid intelligence. A subset of 122 underwent neuroimaging before and after supplementation to measure whole-brain and subcortical tissue volumes.
Results
Capsule adherence was over 95%, participant blinding was verified, and red blood cell EPA and DHA levels increased as expected. Supplementation did not affect performance in any of the four cognitive domains. Exploratory analyses revealed that, compared to placebo, fish oil supplementation improved executive function in participants with low-baseline DHA levels. No changes were observed in any indicator of brain morphology.
Conclusions
In healthy mid-life adults reporting low-dietary intake, supplementation with LCn-3FAs in moderate dose for moderate duration did not affect neuropsychological performance or brain morphology. Whether salutary effects occur in individuals with particularly low-DHA exposure requires further study.
The identification of people at high risk for future mental disorders is accompanied by the imperative to provide stage-adequate treatments that successfully prevent progression to more severe illness stages. Current evidence-based treatments include psychological and psychosocial treatments on one hand as well as pharmacotherapy. The latter is limited by inadequate efficacy and prominent side effects in many cases, making the discovery of novel biological treatment strategies necessary. Such novel treatments need to be safe, effective, characterised by a benign side effect profile and accessible to young people. In this chapter, emerging biological treatment approaches are reviewed and discussed in regard to their potential impact on early intervention and clinical staging. Substances reviewed here include long-chain omega-3 fatty acids (fish oil), n-acetylcysteine (NAC), cannabidiol and repeated transcranial magnetic stimulation (rTMS) with a particular focus on recent advancements in their application in youth with incipient mental disorders. Finally, research priorities in the field of treatment trials are discussed in this chapter.
The staging model of mental illness is developing beyond the clinical level aiming to include biological processes and markers that may reflect the dynamic biological processes of stages of mental illness. The neurobiology of inflammation in mental illness has gained much attention in recent years. Since neuroinflammation has been shown to be an important possible feature of psychosis, schizophrenia and depression, in this chapter it is attempted to map changes and dysregulation of the immune system and inflammation to the different clinical stages of severe mental illness. The literature suggests that an increased inflammatory response may define a subgroup of individuals in ultra-high-risk states, in acute disease episodes and in those with severe mental illness. In addition, the literature clearly points to the dynamic nature of the immune response in mental illness and shows an involvement of both the innate and adaptive immune system in mental illness. A focus on inflammation only might be insufficient and a broader understanding of the interaction between innate and adaptive immune systems and the complex neuroimmune interaction is required.
For over a decade a transdiagnostic clinical staging framework for youth with anxiety, mood and psychotic disorders (linked with measurement of multidimensional outcomes), has been utilised in over 8,000 young people presenting to the enhanced primary (headspace) and secondary care clinics of the Brain and Mind Centre of the University of Sydney. This framework has been evaluated alongside a broad range of other clinical, neurobiological, neuropsychological, brain imaging, circadian, metabolic, longitudinal cohort and controlled intervention studies. This has led to specific tests of its concurrent, discriminant and predictive validity. These extensive data provide strong preliminary evidence that: i) varying stages of illness are associated with predicted differences in a range of independent and objectively measured neuropsychological and other biomarkers (both cross-sectionally and longitudinally); and, ii) that earlier stages of illness progress at variable rates to later and more severe or persistent disorders. Importantly, approximately 15-20% of those young people classed as stage 1b or ‘attenuated’ syndromes at presentation progress to more severe or persistent disorders. Consequently, this cohort should be the focus of active secondary prevention trials. In clinical practice, we are moving to combine the staging framework with likely pathophysiological paths (e.g. neurodevelopmental-psychotic, anxiety-depression, circadian-bipolar) to underpin enhanced treatment selection.
The identification of people at high risk for future mental disorders is accompanied by the imperative to provide stage-adequate treatments that successfully prevent progression to more severe illness stages. Current evidence-based treatments include psychological and psychosocial treatments on one hand as well as pharmacotherapy. The latter is limited by inadequate efficacy and prominent side effects in many cases, making the discovery of novel biological treatment strategies necessary. Such novel treatments need to be safe, effective, characterised by a benign side effect profile and accessible to young people. In this chapter, emerging biological treatment approaches are reviewed and discussed in regard to their potential impact on early intervention and clinical staging. Substances reviewed here include long-chain omega-3 fatty acids (fish oil), n-acetylcysteine (NAC), cannabidiol and repeated transcranial magnetic stimulation (rTMS) with a particular focus on recent advancements in their application in youth with incipient mental disorders. Finally, research priorities in the field of treatment trials are discussed in this chapter.
We report on a 14-year-old boy with focal atrial tachycardia. After failure of catheter ablation and medical therapy he received 2 g omega-3 fatty acid supplementation while waiting on repeat ablation. Focal atrial tachycardia disappeared 4 weeks later and antiarrhythmic therapy was terminated. We discuss the antiarrhythmic effect of omega 3-fatty acids on the autonomous nervous system based upon six 24-hour Holter electrocardiographs.
After MRI studies suggested the efficacy of ethyl-EPA in reducing the progressive brain atrophy in Huntington disease (HD), trials were conducted to test its efficacy as a treatment for HD. Trials that continued for 6 months did not find any significant improvement, urging discontinuation of the drug. However, trials that continued for 12 months indicated improvement of motor functions in these patients.
Methods:
We searched 12 electronic databases to find randomised clinical trials relevant to our inclusion criteria. After screening, only five papers were included. Continuous and binary variables were analysed to compute the pooled mean difference (MD) and risk ratio (RR), respectively. Quality effect model meta-analysis was used as a post hoc analysis for studies at 12 months.
Findings:
Meta-analysis indicated that ethyl-eicosapentaenoic acid (EPA) has no significant effect on any scale of HD at 6 months. At 12 months, two studies suggested significant improvements of the Total Motor Score and Total Motor Score–4 in both fixed and quality effect models [MD = −2.720, 95% CI (−4.76, –.68), p = 0.009; MD = −2.225, 95% CI (−3.842, −0.607), p = 0.007], respectively. Maximal chorea score showed significant results [MD = −1.013, 95% CI (−1.793, −0.233), p = 0.011] in only fixed-effect model, while no improvement was detected for Stroop colour naming test or symbol digit modality.
Conclusion:
Meta-analysis indicated a significant improvement of motor scores only after 12 months. These results should be interpreted cautiously because only two studies had assessed the efficacy of ethyl-EPA after 12 months with one of them having a 6-month open-label phase.
Fish oil contains omega-3 fatty acids, which play a vital role in fetal growth and development. In utero exposure to omega-3 fatty acids is exclusively dependent on maternal nutrition. Previous studies have suggested that prenatal fish oil supplementation has positive impacts on child neurodevelopment later in life. This study examines the associations between fish oil supplementation both before pregnancy and throughout pregnancy and subsequent child development. Mother–child pairs from the Upstate KIDS Study, a birth cohort consisting of children born between 2008 and 2010, were included. Self-reported prenatal fish oil supplementation data were available for 5845 children (3807 singletons and 2038 twins). At multiple time points, from 4 months to 3 years of age, child development was reported by the parents on the Ages and Stages Questionnaire (ASQ). Five developmental domains were assessed: fine motor, gross motor, communication, personal–social functioning and problem solving. Generalized linear mixed models were used to estimate odds ratios (OR) while adjusting for covariates. Primary analyses showed that the risk of failing the ASQ problem-solving domain was significantly lower among children of women who took fish oil before pregnancy (OR 0.40, 95% confidence intervals (CI) 0.18–0.89) and during pregnancy (OR 0.43, 95% CI 0.22–0.83). Gender interaction was not statistically significant, although stratified results indicated stronger associations among girls. Similarly, associations were primarily among singletons. Prenatal fish oil supplementation may be beneficial in regards to neurodevelopment. Specifically, it is associated with a lower risk of failing the problem-solving domain up to 3 years of age.
Asthma is one of the most common and prevalent problems worldwide affecting over 300 million individuals. There is some evidence from observational and intervention studies to suggest a beneficial effect of n-3 PUFA in inflammatory diseases, specifically asthma. Marine-based n-3 PUFA have therefore been proposed as a possible complementary/alternative therapy for asthma. The proposed anti-inflammatory effects of n-3 fatty acids may be linked to a change in cell membrane composition. This altered membrane composition following n-3 fatty acid supplementation (primarily EPA and DHA) can modify lipid mediator generation via the production of eicosanoids with a reduced inflammatory potential/impact. A recently identified group of lipid mediators derived from EPA including E-series resolvins are proposed to be important in the resolution of inflammation. Reduced inflammation attenuates the severity of asthma including symptoms (dyspnoea) and exerts a bronchodilatory effect. There have been no major health side effects reported with the dietary supplementation of n-3 fatty acids or their mediators; consequently supplementing with n-3 fatty acids is an attractive non-pharmacological intervention which may benefit asthma.
Fish is an important source of energy, high-quality proteins, fat, vitamins and minerals. Within lipids, n-3 long-chain PUFA (n-3 LC PUFA), mainly EPA and DHA, play an important role in health promotion and disease prevention. In contrast to the potential health benefits of dietary fish intake, certain chemical pollutants, namely heavy metals and some organic compounds, contained in seafood have emerged as an issue of concern, particularly for frequent fish consumers and sensitive groups of populations. The present review summarises the health benefits and risks of fish consumption. n-3 LC-PUFA are key compounds of cell membranes and play an important role in human health from conception through every stage of human development, maturation and ageing. DHA has a major role in the development of brain and retina during fetal development and the first 2 years of life and positively influences neurodevelopment, mainly visual acuity and cognitive functions. n-3 LC-PUFA are also effective in preventing cardiovascular events (mainly stroke and acute myocardial infarction) especially in persons with high cardiovascular risk. By contrast, there is convincing evidence of adverse neurological/neurodevelopmental outcomes in infants and young children associated with methylmercury exposure during fetal development due to maternal fish consumption during pregnancy. Dioxins and polychlorinated biphenyls present in contaminated fish may also develop a risk for both infants and adults. However, for major health outcomes among adults, the vast majority of epidemiological studies have proven that the benefits of fish intake exceed the potential risks with the exception of a few selected species in sensitive populations.
To conduct a critical review of recent empirical research regarding mood, behaviour and nutrition factors including essential fatty acids, macronutrients, micronutrients and food additives.
Method:
A literature search of databases Medline, PsycInfo, CINAHL and Embase up to October 2008. The search emphasised empirical research published in the last 10 years and also included older literature. Studies in both adults and children were addressed.
Results:
Research into omega-3 fatty acids has been substantial but evidence for their potential in treating mood and behaviour is modest. In comparison, there has been much less research into carbohydrate and protein intakes and little evidence for their ability to influence mood and behaviour. Recent trials with food additives suggest their removal from the diet may benefit susceptible children with hyperactivity disorders. Micronutrient supplementation appears to improve mood only in those who were initially deficient in micronutrients.
Conclusions:
More stringent research designs such as longitudinal studies and the use of biologically inert placebos within randomised controlled trials are needed before supplemental use of omega-3 fatty acids to treat disorders of mood and behaviour can be recommended. Caution is advised regarding the indiscriminate use of diets free of artificial food additives in managing hyperactivity disorders, as they may place an undue burden on individuals and their families. Should omega-3 fatty acid supplementation or the elimination of certain food additives be established as effective, they may provide cost-effective, accessible and well-tolerated adjuncts to standard psychiatric treatments for mood and behavioural disturbances.
This chapter discusses complementary and alternative medicine (CAM) treatments preferred by patients with mood disorders. Omega-3 fatty acids are lower in depressed suicide attempters and completers compared with depressed nonattempters, a concentration-dependent effect, suggesting increased suicide risk in individuals with extremely low omega-3 levels. St. John's wort (SJW) has been extensively studied as a monotherapy for the treatment of depression. Among the CAM treatments, evidence supports the use of SJW as a monotherapy, and omega-3, S-adenosyl-methionine (SAMe), and several methylators as augmentation strategies in the treatment of depression. Methodological flaws are a consistent critique of CAM, and larger, longer-term studies are needed to assess CAM efficacy. Interventions such as yoga, acupuncture, and improved nutrition are inherently difficult to blind, complicating their assessment. Clinical experience suggests that CAM may be helpful in engaging patients and useful in the treatment of carefully selected patients.
Background & Aim: Despite their well known anti-inflammatory actions, the clinical usefulness of omega-3 PUFA in inflammatory bowel disease is controversial. We aimed to systematically review the available data on the performance of omega-3 PUFA as therapeutic agents in these patients. Methods: Electronic databases were systematically searched for RCT of fish oil or omega-3 PUFA therapy in both active and inactive ulcerative colitis or Crohn's disease, without limitation on either the length of therapy or the form it was given, including nutritional supplements and enteral formula diets. Eligible articles were assessed for methodological quality on the basis of the adequacy of the randomisation process, concealment of allocation, blinding of intervention and outcome, possible biases, and completeness of follow-up. The five-point Oxford quality score was calculated. Results: A total of 19 RCT were finally selected for this review. Overall, available data do not allow to support the use of omega-3 PUFA supplementation for the treatment of both active and inactive inflammatory bowel disease. Negative results are quite consistent in trials assessing the use of omega-3 PUFA to maintain disease remission, particularly ulcerative colitis, and to a lesser extent Crohn's disease. Trials on their use in active disease do not allow to draw firm conclusions mainly because the heterogeneity of design (ulcerative colitis) or their short number (Crohn's disease). In most trials, the appropriateness of the selected placebo is questionable. Conclusion: The present systematic review does not allow to make firm recommendations about the usefulness of omega-3 PUFA in inflammatory bowel disease.
Epidemiological and clinical studies suggest that consumption of omega (ω-3) polyunsaturated fatty acids (PUFA) contributes to the reduction of cardiovascular mortality through different mechanisms including modulation of cellular metabolic functions, gene expression and beneficial effects on lipid profile or blood pressure. The aim of the study is to review the effects of ω-3 PUFA supplemented as fish oil or blue fish in blood pressure. The analysis of different studies suggests that high doses ω-3 PUFA ( ≥ 3 g/day) produces a small but significant decrease in blood pressure, especially systolic blood pressure, in older and hypertensive subjects; however, the evidence is not consistent among different studies. ω-3 polyunsaturated fatty acids consumption might have a place in the control of patients with mild hypertension before starting drug treatment and of those who prefer changes of lifestyles like diet.
Some epidemiological evidence suggests that diets high in omega 3 fatty acids (n-3 FAs) may be beneficial for skeletal health. The aim of this systematic review was to determine if randomized controlled trials (RCTs) support a positive effect of n-3 FAs on osteoporosis. A systematic search was performed in PubMed and EMBASE databases. We included RCTs with skeletal outcomes conducted in adults or children (> = 1 year old) using n-3 FA fortified foods, diets or supplements alone or in combination with other vitamins/minerals, versus placebo. Primary outcomes were incident fracture at any site and bone mineral density (BMD) in g/cm2. Secondary outcomes included bone formation or resorption markers and bone turnover regulators. A total of 10 RCTs met inclusion criteria. Effect sizes with 95 % confidence intervals were estimated to compare studies across various treatments and outcome measures. No pooled analysis was completed due to heterogeneity of studies and small sample sizes. No RCTs included fracture as an outcome. Four studies reported significant favorable effects of n-3 FA on BMD or bone turnover markers. Of these, three delivered n-3 FA in combination with high calcium foods or supplements. Five studies reported no differences in outcomes between n-3 FA intervention and control groups; one study included insufficient data for effect size estimation. Strong conclusions regarding n-3 FAs and bone disease are limited due to the small number and modest sample sizes of RCTs, however, it appears that any potential benefit of n-3 FA on skeletal health may be enhanced by concurrent administration of calcium.