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Effect of a Mediterranean diet or mindfulness-based stress reduction during pregnancy on child neurodevelopment: a prespecified analysis of the IMPACT BCN Randomized Clinical Trial. 

Crovetto, F., A. Nakaki, A. Arranz, R. Borras, K. Vellvé, C. Paules, M.L. Boutet, S. Castro-Barquero, T. Freitas, R. Casas, A. Martín-Asuero, T, Oller Guzmán, I. Morilla, A. Martínez-Àran, A. Camacho, M. Pasqual, M. Izquierdo Renau,  Ó.J. Pozo, A. Gomez-Gomez, R. Estruch,  E. Vieta , F. Crispi, E. Gratacós, 2023. Effect of a Mediterranean diet or mindfulness-based stress reduction during pregnancy on child neurodevelopment: a prespecified analysis of the IMPACT BCN Randomized Clinical Trial. JAMA Netw. Open. 6(8):e2330255. https://doi.org/10.1001/jamanetworkopen.2023.30255

Importance: Maternal suboptimal nutrition and high stress levels are associated with adverse fetal and childhood neurodevelopment. Objective: To test the hypothesis that structured interventions based on a Mediterranean diet or mindfulness-based stress reduction (MBSR) during pregnancy improve child neurodevelopment at age 2 years. Design, setting, and participants: This was a prespecified analysis of the parallel-group Improving Mothers for a Better Prenatal Care Trial Barcelona (IMPACT BCN) randomized clinical trial, which was conducted at a university hospital in Barcelona, Spain, from February 2017 to March 2020. A total of 1221 singleton pregnancies (19 to 23 weeks’ gestation) with high risk of delivering newborns who were small for gestational age were randomly allocated into 3 groups: a Mediterranean diet intervention, an MBSR program, or usual care. A postnatal evaluation with the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III), was performed. Data were analyzed from July to November 2022. Interventions: Participants in the Mediterranean diet group received monthly individual and group educational sessions and free provision of extra virgin olive oil and walnuts. Those in the stress reduction group underwent an 8-week MBSR program adapted for pregnancy. Individuals in the usual care group received pregnancy care per institutional protocols. Main outcomes and measures: Neurodevelopment in children was assessed by Bayley-III at 24 months of corrected postnatal age. Results: A total of 626 children (293 [46.8%] female and 333 [53.2%] male) participated at a mean (SD) age of 24.8 (2.9) months. No differences were observed in the baseline characteristics between intervention groups. Compared with children from the usual care group, children in the Mediterranean diet group had higher scores in the cognitive domain (β, 5.02; 95% CI, 1.52-8.53; P = .005) and social-emotional domain (β, 5.15; 95% CI, 1.18-9.12; P = .01), whereas children from the stress reduction group had higher scores in the social-emotional domain (β, 4.75; 95% CI, 0.54-8.85; P = .02). Conclusions and relevance: In this prespecified analysis of a randomized clinical trial, maternal structured lifestyle interventions during pregnancy based on a Mediterranean diet or MBSR significantly improved child neurodevelopmental outcomes at age 2 years.

Effect of walnut consumption on neuropsychological development in healthy adolescents: a multi-school randomised controlled trial.

Pinar-Martí, A., F. Gignac, S. Fernández-Barrés, D. Romaguera, A. Sala-Vila, I. Lázaro, O.T. Ranzani, C. Persavento, A. Delgado, A. Carol, J. Torrent, J. Gonzalez, E. Roso, J. Barrera-Gómez, M. López-Vicente, O. Boucher, M. Nieuwenhuijsen, M.C. Turner, M. Burgaleta, J. Canals, V. Arija, X. Basagaña, E. Ros, J. Salas-Salvadó, J. Sunyer, J. Julvez, 2023. Effect of walnut consumption on neuropsychological development in healthy adolescents: a multi-school randomised controlled trial. eClinicalMedicine. 59:101954. https://doi.org/10.1016/j.tjnut.2023.01.003

Background: Omega-3 fatty acids are critical for neuropsychological functioning. Adolescence is increasingly believed to entail brain vulnerability to dietary intake. The potential benefit on adolescent neurodevelopment of consuming walnuts, a source of omega-3 alpha-linolenic acid (ALA), remains unclear. Methods: We conducted a 6-month multi-school-based randomised controlled nutrition intervention trial to assess whether walnut consumption has beneficial effects on the neuropsychological and behavioural development of adolescents. The study took place between 04/01/2016 and 06/30/2017 in twelve different high schools in Barcelona, Spain (ClinicalTrials.gov Identifier: NCT02590848). A total of 771 healthy teenagers aged 11–16 years were randomised into two equal groups (intervention or control). The intervention group received 30 g/day of raw walnut kernels to be incorporated into their diet for 6 months. Multiple primary endpoints concerning neuropsychological (working memory, attention, fluid intelligence, and executive function) and behavioural (socioemotional and attention deficit hyperactivity disorder [ADHD] symptoms) development were assessed at baseline and after intervention. Red blood cell (RBC) ALA status was determined at baseline and 6 months as a measure of compliance. Main analyses were based on intention-to-treat using a linear mixed-effects model. A per-protocol effect of the intervention was analysed using inverse-probability weighting to account for post-randomisation prognostic factors (including adherence) using generalised estimating equations. Findings: In intention-to-treat analyses, at 6 months there were no statistically significant changes between the intervention and control groups for all primary endpoints. RBC ALA (%) significantly increased only in the intervention group, coefficient = 0.04 (95% Confidence Interval (CI) = 0.03, 0.06; p < 0.0001). The per-protocol (adherence-adjusted) effect on improvement in attention score (hit reaction time variability) was −11.26 ms (95% CI = −19.92, −2.60; p = 0.011) for the intervention group as compared to the control group, improvement in fluid intelligence score was 1.78 (95% CI = 0.90, 2.67; p < 0.0001), and reduction of ADHD symptom score was −2.18 (95% CI = −3.70, −0.67; p = 0.0050). Interpretation: Our study suggested that being prescribed eating walnuts for 6 months did not improve the neuropsychological function of healthy adolescents. However, improved sustained attention, fluid intelligence, and ADHD symptoms were observed in participants who better complied with the walnut intervention. This study provides a foundation for further clinical and epidemiological research on the effect of walnuts and ALA on neurodevelopment in adolescents.

Dietary walnuts preserve aspects of health span and alter the hippocampal lipidome in aged high-fat diet-fed mice.

Novaj, A., M.G. Engel, R. Wang, K. Mao, X. Xue, Y. Amir, G. Atzmon, D.M. Huffman, 2023. Dietary walnuts preserve aspects of health span and alter the hippocampal lipidome in aged high-fat diet-fed mice. International Journal of Molecular Sciences. 24(3):2314. https://doi.org/10.3390/ijms24032314

Evidence continues to accrue that aging and its diseases can be delayed by pharmacologic and dietary strategies that target the underlying hallmarks of the aging process. However, identifying simple, safe, and effective dietary strategies involving the incorporation of whole foods that may confer some protection against the aging process is also needed. Recent observational studies have suggested that nut consumption can reduce mortality risk in humans. Among these, walnuts are particularly intriguing, given their high content of n-3 fatty acids, fiber, and antioxidant and anti-inflammatory compounds. To this end, 12-month-old male CB6F1 mice were provided either a defined control low-fat diet (LFD), a control high-fat diet (HFD), or an isocaloric HFD containing 7.67% walnuts by weight (HFD + W), and measures of health span and related biochemical markers (n = 10-19 per group) as well as survival (n = 20 per group) were monitored. Mice provided the HFD or HFD + W demonstrated marked weight gain, but walnuts lowered baseline glucose (p < 0.05) and tended to temper the effects of HFD on liver weight gain (p < 0.05) and insulin tolerance (p = 0.1). Additional assays suggested a beneficial effect on some indicators of health with walnut supplementation, including preservation of exercise capacity and improved short-term working memory, as determined by Y maze (p = 0.02). However, no effect was observed via any diet on inflammatory markers, antioxidant capacity, or survival (p = 0.2). Ingenuity Pathway Analysis of the hippocampal transcriptome identified two processes predicted to be affected by walnuts and potentially linked to cognitive function, including estrogen signaling and lipid metabolism, with changes in the latter confirmed by lipidomic analysis. In summary, while walnuts did not significantly improve survival on a HFD, they tended to preserve features of health span in the context of a metabolic stressor with aging.

Key Area: Cognitive Health

Effect of a Mediterranean diet or mindfulness-based stress reduction during pregnancy on child neurodevelopment: A prespecified analysis of the IMPACT BCN Randomized Clinical Trial.

Crovetto, F., A. Nakaki, A. Arranz, R. Borras, K. Vellvé, C. Paules, M.L. Boutet, S. Castro-Barquero, T. Freitas, R. Casas, A. Martín-Asuero, T. Oller Guzmán, I. Morilla, A. Martínez-Àran, A. Camacho, M. Pasqual, M. Izquierdo Renau, Ó. J. Pozo, A. Gomez-Gomez, R. Estruch, E. Vieta, F. Crispi, E. Gratacós, 2023. Effect of a Mediterranean diet or mindfulness-based stress reduction during pregnancy on child neurodevelopment: A prespecified analysis of the IMPACT BCN Randomized Clinical Trial. JAMA Network Open, 6(8), e2330255. https://doi.org/10.1001/jamanetworkopen.2023.30255

Importance: Maternal suboptimal nutrition and high stress levels are associated with adverse fetal and childhood neurodevelopment. Objective: To test the hypothesis that structured interventions based on a Mediterranean diet or mindfulness-based stress reduction (MBSR) during pregnancy improve child neurodevelopment at age 2 years. Design, setting, and participants: This was a prespecified analysis of the parallel-group Improving Mothers for a Better Prenatal Care Trial Barcelona (IMPACT BCN) randomized clinical trial, which was conducted at a university hospital in Barcelona, Spain, from February 2017 to March 2020. A total of 1221 singleton pregnancies (19 to 23 weeks’ gestation) with high risk of delivering newborns who were small for gestational age were randomly allocated into 3 groups: a Mediterranean diet intervention, an MBSR program, or usual care. A postnatal evaluation with the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III), was performed. Data were analyzed from July to November 2022. Interventions: Participants in the Mediterranean diet group received monthly individual and group educational sessions and free provision of extra virgin olive oil and walnuts. Those in the stress reduction group underwent an 8-week MBSR program adapted for pregnancy. Individuals in the usual care group received pregnancy care per institutional protocols. Main outcomes and measures: Neurodevelopment in children was assessed by Bayley-III at 24 months of corrected postnatal age. Results: A total of 626 children (293 [46.8%] female and 333 [53.2%] male) participated at a mean (SD) age of 24.8 (2.9) months. No differences were observed in the baseline characteristics between intervention groups. Compared with children from the usual care group, children in the Mediterranean diet group had higher scores in the cognitive domain (β, 5.02; 95% CI, 1.52-8.53; P = .005) and social-emotional domain (β, 5.15; 95% CI, 1.18-9.12; P = .01), whereas children from the stress reduction group had higher scores in the social-emotional domain (β, 4.75; 95% CI, 0.54-8.85; P = .02). Conclusions and relevance: In this prespecified analysis of a randomized clinical trial, maternal structured lifestyle interventions during pregnancy based on a Mediterranean diet or MBSR significantly improved child neurodevelopmental outcomes at age 2 years.

Key Area: Cognitive Health

Longer-term mixed nut consumption improves brain vascular function and memory: A randomized, controlled crossover trial in older adults.

Nijssen, K.M.R., R.P. Mensink, J. Plat, P.J. Joris, 2023. Longer-term mixed nut consumption improves brain vascular function and memory: A randomized, controlled crossover trial in older adults. Clin Nutr. 42(7):1067-1075. https://doi.org/10.1016/j.clnu.2023.05.025

Background: Nut consumption may reduce age-related cognitive decline, but underlying mechanisms are unclear. Objective: To investigate in older adults longer-term effects of mixed nut consumption on brain vascular function, which may underlie improvements in cognitive performance. Methods: Twenty-eight healthy individuals (age [mean ± SD]: 65 ± 3 years; BMI: 27.9 ± 2.3 kg/m2) were included in a randomized, single-blinded, cross-over trial with a 16-week intervention (60 g/d mixed nuts: walnuts, pistachio, cashew, and hazelnuts) and control period (no nuts), separated by 8 weeks of washout. Participants followed the Dutch food-based dietary guidelines. At the end of each period, cerebral blood flow (CBF), a marker of brain vascular function, was quantified using arterial spin labeling magnetic resonance imaging. Effects on endothelial function, arterial stiffness, and the retinal micro vasculature were also assessed. Cognitive performance was measured using the Cambridge Neuropsychological Test Automated Battery. Results: Body weight remained stable during the study. As compared to the control period, the mixed nut intervention resulted in a higher regional CBF in the right frontal and parietal lobes (treatment effect: 5.0 ± 6.5 mL/100 g/min; P < 0.001), left frontal lobe (5.4 ± 7.1 mL/100 g/min; P < 0.001), and bilateral prefrontal cortex (5.6 ± 6.6 mL/100 g/min; P < 0.001). Carotid artery reactivity (0.7 PP; 95% CI: 0.2 to 1.2; P = 0.007), brachial flow-mediated vasodilation (1.6 PP; 95% CI: 1.0 to 2.2; P < 0.001) and retinal arteriolar calibers were higher (2 µm; 95% CI: 0 to 3; P = 0.037), and carotid-to-femoral pulse wave velocity lower (− 0.6 m/s; 95% CI: −1.1 to −0.1; P = 0.032). Further, visuospatial memory (− 4 errors [16%]; 95%CI: −8 to 0; P = 0.045) and verbal memory (+1 correct [16%]; 0 to 2; P = 0.035) improved, but executive function and psychomotor speed did not change. Conclusions: Longer-term mixed nut consumption as part of a healthy diet beneficially affected brain vascular function, which may relate to the observed beneficial effects on memory in older adults. Moreover, different characteristics of the peripheral vascular tree also improved.

Mixed nuts as healthy snacks: effect on tryptophan metabolism and cardiovascular risk factors.

Yang, J., R. Lee, Z. Schulz, A. Hsu, J. Pai, S. Yang, S.M. Henning, J. Huang, J.P. Jacobs, D. Heber, Z. Li., 2023. Mixed nuts as healthy snacks: effect on tryptophan metabolism and cardiovascular risk factors. Nutrients. 15, 569; https://doi.org/10.3390/nu15030569.

We recently demonstrated that the consumption of mixed tree nuts (MTNs) during caloric restriction decreased cardiovascular risk factors and increased satiety. Tryptophan (Trp) metabolism has been indicated as a factor in cardiovascular disease. Here, we investigated the effect of MTNs on Trp metabolism and the link to cardiovascular risk markers. Plasma and stool were collected from 95 overweight individuals who consumed either MTNs (or pretzels) daily as part of a hypocaloric weight loss diet for 12 weeks followed by an isocaloric weight maintenance program for an additional 12 weeks. Plasma and fecal samples were evaluated for Trp metabolites by LC–MS and for gut microbiota by 16S rRNA sequencing. Trp–kynurenine metabolism was reduced only in the MTNs group during weight loss (baseline vs. week 12). Changes in Trp–serotonin (week 24) and Trp–indole (week 12) metabolism from baseline were increased in the MTNs group compared to the pretzel group. Intergroup analysis between MTN and pretzel groups does not identify significant microbial changes as indicated by alpha diversity and beta diversity. Changes in the relative abundance of genus Paludicola during intervention are statistically different between the MTNs and pretzel group with p < 0.001 (q = 0.07). Our findings suggest that consumption of MTNs affects Trp host and microbial metabolism in overweight and obese subjects.

Walnut oil reduces Aβ levels and increases neurite length in a cellular model of early Alzheimer disease. 

Esselun, C., F. Dieter, N. Sus, J. Frank, G.P. Eckert, 2022. Walnut oil reduces Aβ levels and increases neurite length in a cellular model of early Alzheimer disease. Nutrients. 14(9):1694. https://doi.org/10.3390/nu14091694

Background: Mitochondria are the cells’ main source of energy. Mitochondrial dysfunction represents a key hallmark of aging and is linked to the development of Alzheimer’s disease (AD). Maintaining mitochondrial function might contribute to healthy aging and the prevention of AD. The Mediterranean diet, including walnuts, seems to prevent age-related neurodegeneration. Walnuts are a rich source of α-linolenic acid (ALA), an essential n3-fatty acid and the precursor for n3-long-chain polyunsaturated fatty acids (n3-PUFA), which might potentially improve mitochondrial function. Methods: We tested whether a lipophilic walnut extract (WE) affects mitochondrial function and other parameters in human SH-SY5Y cells transfected with the neuronal amyloid precursor protein (APP695). Walnut lipids were extracted using a Soxhlet Extraction System and analyzed using GC/MS and HPLC/FD. Adenosine triphosphate (ATP) concentrations were quantified under basal conditions in cell culture, as well as after rotenone-induced stress. Neurite outgrowth was investigated, as well as membrane integrity, cellular reactive oxygen species, cellular peroxidase activity, and citrate synthase activity. Beta-amyloid (Aβ) was quantified using homogenous time-resolved fluorescence. Results: The main constituents of WE are linoleic acid, oleic acid, α-linolenic acid, and γ- and δ-tocopherol. Basal ATP levels following rotenone treatment, as well as citrate synthase activity, were increased after WE treatment. WE significantly increased cellular reactive oxygen species but lowered peroxidase activity. Membrane integrity was not affected. Furthermore, WE treatment reduced Aβ1–40 and stimulated neurite growth. Conclusions: WE might increase ATP production after induction of mitochondrial biogenesis. Decreased Aβ1–40 formation and enhanced ATP levels might enhance neurite growth, making WE a potential agent to enhance neuronal function and to prevent the development of AD. In this sense, WE could be a promising agent for the prevention of AD.

The effects of walnuts and academic stress on mental health, general well-being and the gut microbiota in a sample of university students: a randomised clinical trial.

Herselman, M. F., S. Bailey, P. Deo, X.F. Zhou, K.M. Gunn, L. Bobrovskaya, 2022. The effects of walnuts and academic stress on mental health, general well-being and the gut microbiota in a sample of university students: a randomised clinical trial. Nutrients. 14(22):4776. https://doi.org/10.3390/nu14224776

Poorer mental health is common in undergraduate students due to academic stress. An interplay between stress and diet exists, with stress influencing food choices. Nutritional interventions may be effective in preventing mental health decline due to complex bidirectional interactions between the brain, the gut and the gut microbiota. Previous studies have shown walnut consumption has a positive effect on mental health. Here, using a randomized clinical trial (Australian New Zealand Clinical Trials Registry, #ACTRN12619000972123), we aimed to investigate the effects of academic stress and daily walnut consumption in university students on mental health, biochemical markers of general health, and the gut microbiota. We found academic stress had a negative impact on self-reported mood and mental health status, while daily walnut consumption improved mental health indicators and protected against some of the negative effects of academic stress on metabolic and stress biomarkers. Academic stress was associated with lower gut microbial diversity in females, which was improved by walnut consumption. The effects of academic stress or walnut consumption in male participants could not be established due to small numbers of participants. Thus, walnut consumption may have a protective effect against some of the negative impacts of academic stress, however sex-dependent mechanisms require further study.

The effect of a high-polyphenol Mediterranean diet (Green-MED) combined with physical activity on age-related brain atrophy: the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT PLUS).

Kaplan, A., H. Zelicha, A. Yaskolka Meir, E. Rinott, G. Tsaban, G. Levakov, O. Prager, M. Salti, Y. Yovell, J. Ofer, S. Huhn, F. Beyer, V. Witte, A. Villringer, N. Meiran, T.B. Emesh, P. Kovacs, M. von Bergen, U. Ceglarek, M. Blüher, M. Stumvall, F.B. Hu, M.J. Stampfer, A. Friedman, I. Shelef, G. Avidan, I. Shai, 2022. The effect of a high-polyphenol Mediterranean diet (Green-MED) combined with physical activity on age-related brain atrophy: the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT PLUS). Am. J. Clin. Nutr. 115(5):1270–1281. https://doi.org/10.1093/ajcn/nqac001

Background: The effect of diet on age-related brain atrophy is largely unproven. Objective: To explore the effect of a Mediterranean diet higher in polyphenols and lower in red/processed meat (Green-MED diet) on age-related brain atrophy. Methods: This 18-month clinical trial longitudinally measured brain structure volumes by magnetic-resonance-imaging using hippocampal-occupancy (HOC) and lateral-ventricle-volume (LVV) expansion scores as neurodegeneration markers. Abdominally obese/dyslipidemic participants were randomly assigned to (1)-healthy dietary guidelines (HDG), (2)-Mediterranean (MED) diet, or (3)-Green-MED diet (MED diet higher in polyphenols and lower in red/processed meat). All subjects received free gym memberships and physical activity guidance. Both MED groups consumed 28g/day walnuts (+440 mg/d polyphenols). The Green-MED group consumed green-tea (3-4 cups/day) and Mankai (Wolffia-globosa strain, 100g frozen-cubes/day) green shake (+800mg/day polyphenols). Results: Among 284 participants (age = 51years; 88% men; BMI = 31.2kg/m2; apolipoprotein E-ε4 genotype = 15.7%), 224 (79%) completed the trial with eligible whole-brain MRIs. The pallidum (-4.2%), third ventricle (+3.9%), and LVV (+2.2%) disclosed the largest volume changes. Compared to younger participants, atrophy was accelerated among those ≥ 50 years [HOC change = -1.0±1.4% vs. -0.06±1.1%; 95% confidence-interval (CI):0.6, 1.3; p<0.001; LVV change = 3.2±4.5% vs. 1.3±4.1%; 95%CI:-3.1, -0.8;p = 0.001]. In subjects ≥50years, HOC decline and LVV expansion were attenuated in both MED groups, with the best outcomes among Green-MED diet participants, as compared to HDG (HOC: -0.8±1.6% vs. -1.3±1.4%;95%CI: -1.5, -0.02;p = 0.042, LVV: 2.3±4.7% vs. 4.3±4.5;95%CI;0.3, 5.2;p = 0.021). Similar patterns were observed among younger subjects. Improved insulin sensitivity over the trial was the strongest parameter associated with brain atrophy attenuation (p<0.05). Greater Mankai, green-tea and walnuts intake and less red and processed meat were significantly and independently associated with reduced HOC decline (p<0.05). Elevated urinary levels of the Mankai-derived polyphenols: urolithin-A (r = 0.24;p = 0.013) and tyrosol (r = 0.26;p = 0.007) were significantly associated with lower HOC decline. Conclusions: A Green-MED, high-polyphenol diet, rich in Mankai, green tea and walnuts and low in red/processed meat is potentially neuroprotective for age-related brain atrophy.

Impact of α-linolenic acid, the vegetable ω-3 fatty acid, on cardiovascular disease and cognition.

Sala-Vila, A., J. Fleming, P. Kris-Etherton, E. Ros, 2022. Impact of α-linolenic acid, the vegetable ω-3 fatty acid, on cardiovascular disease and cognition. Adv. Nutr. 13(5):1584–1602. https://doi.org/10.1093/advances/nmac016

Given the evidence of the health benefits of plant-based diets and long-chain n-3 fatty acids, there is keen interest in better understanding the role of alpha-linolenic acid (ALA), a plant-derived n-3 fatty acid, on cardiometabolic diseases and cognition. There is increasing evidence for ALA largely based on its major food sources (i.e., walnuts and flaxseed); however, this lags behind our understanding of long-chain n-3 fatty acids. Meta-analyses of observational studies have shown that increasing dietary ALA is associated with a 10% lower risk of total cardiovascular disease and a 20% reduced risk of fatal coronary heart disease. Three randomized controlled trials (Alpha Omega trial, Prevención con Dieta Mediterránea [PREDIMED] trial, and Lyon Diet Heart Study) all showed benefits of diets high in ALA on cardiovascular-related outcomes, but the Alpha Omega trial, designed to specifically evaluate ALA effects, only showed a trend for benefit. Randomized controlled trials have shown that dietary ALA reduced total cholesterol, low-density-lipoprotein cholesterol, triglycerides, and blood pressure, and epidemiological studies and some trials also have shown an anti-inflammatory effect of ALA; which collectively account for, in part, the cardiovascular benefits of ALA. A meta-analysis reported a trend toward diabetes risk reduction with both dietary and biomarker ALA. For metabolic syndrome and obesity, the evidence for ALA benefits is inconclusive. The role of ALA in cognition is in the early stages but shows promising evidence of counteracting cognitive impairment. Much has been learned about the health benefits of ALA and with additional research we will be better positioned to make strong evidence-based dietary recommendations for the reduction of many chronic diseases.