So, prepare for a revelation beyond the emojis — lycopene might just be the missing piece in the puzzle of cognitive brilliance! Link to studies here. Spice up your kitchen with a dash of cognitive magic! Transform your meals into vibrant, brain-boosting experiences with tomato-centric recipes stealing the spotlight.

Your kitchen is about to become the stage for a delicious symphony of flavors and well-being. In our research journey, we encounter challenges — limitations, individual quirks, and potential side effects.

Much like any adventure, we need to be mindful of existing research limitations, respect individual variations, and consider potential side effects. You can find more research and studies published here. As we wrap up this tomato-filled saga, consider it an invitation for your brain to embark on a flavorful and potentially brain-boosting journey.

Therefore, the present research study was proposed based on the rationale that many fat-soluble nutrients carotenoids, vitamins A, E, K, and fatty acids [FA] are present in human brain 26 — 31 , and that they are a part of dietary patterns and serum NPs previously reported to be associated with better cognitive function in multiple aging cohorts 2 , 15 , 26 , 28 , 32 , to date 34 , Subsequently, the relationship between constructed NPs and cognitive performance at the time point closest to death was cross-sectionally investigated.

Findings from this novel study may also provide insights into the role of nutrition in cognition in the oldest old, which may be similar or different from lesser aged older adults. The design of GCS, objectives, protocols of subject recruitment, and brain collection have been previously described in detail 34 , Briefly, the GCS was a population-based study conducted in 44 counties in northern Georgia.

The GCS was primarily designed to identify biological, psychological, and social factors contributing to survivorship and successful aging. Brain tissues from frontal FC and temporal cortices TC were collected from 47 subjects who were a subset of centenarians enrolled in the phase III of the GCS — and gave consent to donate brain tissue upon death.

All protocols were performed with an approval from the University of Georgia Institutional Review Board. Protocols for brain lipid extraction, separation, quantification, and concentrations have been previously and separately described for carotenoids, vitamin A retinol , vitamin E α- and γ-tocopherol [TP] , vitamin K phylloquinone [PK] and menaquinone-4 [MK-4] , and individual FAs 27 , 28 , 36 — In short, separation and quantification of five major dietary carotenoids lutein, zeaxanthin, cryptoxanthin, β-carotene, and lycopene , retinol, and TPs were performed using high-performance liquid chromatography HPLC coupled with a photodiode array detector.

The limit of detection LOD was 0. Only levels of the all- trans isomer of each carotenoid, which is the most predominant isomer in human brain tissues, are reported 26 , Separation and detection of PK and MK-4 were performed using HPLC coupled with a fluorescence detector. The LOD was 0.

Total saturated FAs SFAs represent the sum of , , , , , , , , and Total monounsaturated FAs MUFAs represent the sum of n-9 , n-7 , n-9 , n-7 , n-9 , n-9 , and n Total omega-3 polyunsaturated FAs n-3 PUFAs represent the sum of , , , , , and Total omega-6 polyunsaturated FAs n-6 PUFAs represent the sum of , , , , , , , and After enrollment in the GCS, cognitive assessment was performed every 6 months at the subject's residence as reported earlier Dementia status was assessed by geriatric psychiatrists using Global Deterioration Scale GDS and subjects were grouped based on GDS score.

A score of 1—2 on GDS was clinically defined as no dementia; a score of 3 represented mild cognitive impairment; and a score of 4—7 represented increasing severity of dementia from mild to severe Depression was assessed using Geriatric Depression Scale Short Form GDSSF 50 , and activities of daily living were assessed using Direct Assessment of Function Status DAFS All subtests have been validated and are considered reliable measures of cognition in normal aging and in AD To calculate cognitive domain composite scores, scores from each cognitive test were normalized using z-scoring as previously reported Composite scores of five cognitive domains memory, executive function, language, visuospatial function, attention , depression, and activities of daily living were then calculated by averaging the z-scores of tests based on the method adapted from Bowman et al.

The calculation method has also previously been reported and shown in Supplementary Table 1. Global cognition composite scores were also derived by combining total cognitive testing z-scores, MMSE, and SIB.

Missing test scores were excluded and the denominator changed accordingly for the calculation of composite scores. Values are presented as mean SD.

All statistical tests were performed in R 3. Concentrations of all nutrients were log transformed prior to PCA. Nutrient concentration matrix was unit-variance scaled and centered. We chose non-linear iterative partial least squares algorithm to calculate principal components, or NPs in our case, which is an iterative approach for estimating independent principal components by extracting them one at a time This variation of PCA can handle small amount of missing values, which in our case were PK and MK-4 concentrations from two individuals due to insufficient brain tissues for vitamin K analysis.

To investigate the relationship between brain nutrient concentrations or NPs and cognitive domain composite scores, Pearson's correlation test was performed with an adjustment for covariates sex, education, hypertension, diabetes, and presence of APOE ε 4 allele.

Additional adjustment for antithrombotic use was performed for vitamin K, and antidepressant use for depression score. Sub-analyses in non-demented GDS 1—3 were also performed. Heat maps aided the visualization of correlations.

Characteristics of all 47 subjects are reported in Table 1. Seventy percent were institutionalized at the visit closest to death. Body mass index BMI was Twelve subjects, ten of whom had dementia, could not provide data on history of smoking and alcohol use through recall.

Only one subject was an active smoker at death. Concentrations of nutrients averaged from the FC and TC are reported in Table 2 vitamin K only from FC. These data have also been previously reported separately for FC and TC 27, 31, Lutein was the most predominant carotenoid in all FC and TC tissues with a concentration of On the contrary, lycopene, at an average concentration of Retinol, which included both free retinol, retinal, and retinyl esters before hydrolyzation during lipid extraction, had a concentration of While MK-4 was detectable in all brain tissues at 4.

The predominant class of FA in the brain samples was SFA, which accounted for Concentrations of individual FAs are shown in Supplementary Table 2. Docosahexaenoic acid DHA, n-3 and arachidonic acid AA, n-6 were the most predominant n-3 PUFA Concentrations of each nutrient were not significantly different among demented and demented subjects.

Table 2. Mean SD of nutrient concentrations averaged from the frontal and temporal cortices vitamin K only in the frontal cortex. As shown in Figure 1 , significant correlations were identified among concentrations of carotenoids, and among FAs blue represents positive and red represents negative correlations.

These correlations among nutrient concentrations further warranted the investigation of nutrients as NPs. Figure 1. Log transformation has been applied to all nutrient concentrations.

SFA, saturated fatty acid; MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acid; trans -FA, trans -fatty acid. Next, PCA was used to derive NPs from brain nutrient concentrations. No obvious outlier was detected in a PCA plot data not shown.

NP1 which has the highest variance accounted for The correlations of these nutrients in each NP are as depicted in Figure 1. The first five NPs accounted for Table 3. Further, the composite scores for cognitive domains, depression, and activities of daily living had been calculated Supplementary Table 3.

Subjects with GDS 1—3 had significantly higher composite scores on all six cognitive domains and activities of daily living, and significantly lower scores on depression less depression. Scores of the first five NPs were not statistically different between demented and non-demented subjects data not shown.

A heat map was constructed to provide Pearson's partial correlation coefficients between NP scores or nutrient concentrations and scores on cognitive domains, depression, and activities of daily living in all subjects Figure 2A , p -values provided in Supplementary Table 4A. Pearson's partial correlations were adjusted for sex, education, diabetes, hypertension, and presence of APOE ε 4 allele.

No consistent relationship between NPs and cognitive domain scores that reached statistical significance was observed. Figure 2. A subset analysis among non-demented subjects GDS 1—3 was performed and Pearson's coefficients are illustrated in a heat map Figure 2B , p -values provided in Supplementary Table 4B.

Since NP2 is mainly described by carotenoids, significant correlations were also consistently observed between lutein, zeaxanthin, β-carotene and scores on global cognition, memory, language, and depression. Other notable associations included NP3 and NP5 and higher depression.

Figure 3. Pearson's correlation coefficients are adjusted for sex, education, diabetes, hypertension, and APOE ε4 allele. This study documents that brain NP high in carotenoids was consistently associated with better performance on multiple cognitive domains, activities of daily living, and lower depression among non-demented older adults in the GCS.

Results also confirm previously established positive relationships between serum and brain concentrations of carotenoids in this group of subjects independent of their cognitive status Given that serum concentrations of carotenoids likely reflect their habitual intake in the oldest old as previously discussed 27 , our findings in the present study underscore the timing of intervention with diet high in carotenoid content before the onset of age-related dementia.

This is further supported by the fact that nutrient concentrations and NP scores were not different between demented and non-demented subjects. Our exploratory findings also corroborate previous findings where serum levels of carotenoids are positively associated with better cognition in aging subjects 26 , 32 , 57 — Specifically, higher serum lutein concentration was reported to be associated with better performance on language 32 , which is similar to the correlation between NP2 and language score in this study.

The present analysis investigated concentrations of nutrients in the brain, the organ most relevant to cognition, as compared to previous studies that have established dietary or serum NPs with similar exploratory approaches 10 , 11 , 13 , Although the relationship between better adherence to a priori hypothesized intake patterns such as MeDi, HDI, HEI, DASH, MIND and lower risk of cognitive decline have been established 2 , a priori hypothesized NPs are difficult with brain concentrations since little is known regarding nutrient uptake across the BBB and nutrient metabolism in neural tissue.

For instance, SFAs and MUFAs can be de novo synthesized in the liver and CNS and may not reflect intake levels 61 , and among n-3 PUFAs, DHA preferentially accumulates in neural tissue 62 , While substitution of SFA and trans -FA intakes with MUFAs and PUFAs decreases risk of age-related cognitive impairment in many prospective cohorts 64 , our findings with brain content cannot be directly compared with intake levels of SFAs and MUFAs.

It has also been reported that higher SFA content in membranes is usually associated with higher PUFA content to maintain membrane stability 65 , 66 , which likely explains the high correlation between SFA and unsaturated FA observed in the GCS brain tissues.

Similarly, retinol is thought to be either taken up into the brain by STRA6, a retinol-binding protein-receptor detected at the BBB or derived directly from the cleavage of provitamin A carotenoids β-carotene and β-cryptoxanthin by the enzyme BCO1 detected in human brain 67 , It remains unknown how much each source contributes to vitamin A content in the brain.

Moreover, a previous report on vitamin K metabolism in rat cerebellum also suggests that neural MK-4 content is regulated by the enzyme UBIAD1 Overall, findings of nutrient levels in neural tissue need to be cautiously interpreted for dietary recommendations, especially for nutrients that can be derived from other substrates and nutrients whose levels are tightly regulated in the brain.

Data on dietary intake in the GCS have been previously reported However, the dietary assessment was subjective and might have overestimated or underestimated food intake, particularly in this population with varying degrees of cognitive performance.

As a result, dietary intake data were not incorporated into the present analysis. Age-related cognitive impairment, notwithstanding mixed clinical pathologies, shares molecular signatures of increased oxidative stress and neuroinflammation 71 , Both carotenoids and n-3 PUFAs, especially lutein and DHA both of which are selectively accumulated in the brain, have been proposed to interfere with the progression of cognitive impairment in aging, presumably owing to their antioxidative and anti-inflammatory properties 73 , Consistent with previous studies investigating neural concentrations of individual nutrients, a significant relationship was observed with lower carotenoids mainly lutein and zeaxanthin among cognitively impaired or demented subjects 26 , 75 — However, as previously discussed by Zamroziewicz and Barbey 22 , univariate analytical approach with individual nutrients may be confounded by the effect of NPs and does not address the potentially interactive effects of multiple nutrients on cognitive health.

An exploratory trial demonstrates that a combination of lutein and DHA supplements statistically improved performance on memory and learning in cognitively unimpaired elder women after 4 months whereas lutein or DHA supplement alone did not Moreover, most individuals predominantly acquire nutrients from dietary sources that consist of a complex combination of nutrients.

While a 6-month intervention with a lutein and zeaxanthin supplement failed to improve cognitive outcomes in subjects with or without Alzheimer's disease 80 , a daily intervention with an avocado a highly bioavailable source of 0. In the present analysis, a multivariate analysis approach PCA has been adopted to address correlations among nutrients and inspect the nutrition variable as NPs which reflect how multiple nutrients may synergistically function in the context of cognitive functioning and age-related cognitive impairment.

This is an important step in the field of nutritional cognitive neuroscience toward the application of emerging technologies such as metabolomics and brain magnetic resonance imaging to systematically identify underlying mechanisms that mediate the effect that a combination of nutrients have on clinical outcomes 22 , We acknowledge that this exploratory study is limited by a relatively small sample size which is reflected by borderline significant p -values in Supplementary Table 4B of mostly Caucasian women, and the inability to control for other covariates that may affect cognitive function such as alcohol and smoking history, physical activity, social interactions, and genetics However, nutrient profiles and concentrations in this current analysis are similar to those of other cohorts of older adults 29 — 31 , 84 — NP1, described mostly by high fat content, was not associated with cognition in this population.

Previous studies have reported benefits of diets high in n-3 PUFAs, especially DHA, on cognitive health 33 , While it is more appropriate to use absolute concentrations of FAs in the PCA, relative concentrations of FAs i.

Additionally, it is unclear if the FA compositions in the brain of this cohort of the oldest old were in the normal range, since altered fatty acid compositions among cognitively impaired or demented subjects were reported 29 — 31 , but no difference were observed between those with and without dementia in this study.

Other nutrients and dietary compounds such as B vitamins, vitamin D, minerals, and polyphenols that may be beneficial to cognitive health were also not examined in this study 90 , but propose the opportunity to expand the scope of investigation.

Nutrients that are not present in the brain but sharing common dietary sources with carotenoids and n-3 PUFAs, such as fibers in fruits, vegetables, nuts and seeds, may provide additional benefits to the central nervous system by functioning systemically through the regulation of reverse cholesterol transport, gut microbiota, and gut-brain axis signaling 91 , Finally, a cross-sectional study does not address a causal and longitudinal relationship between nutrition and cognition.

A reverse causation where cognitive impairment leads to changes in nutrient uptake and metabolism—for example through BBB breakdown—is possible However, dietary intervention in human trials and animal studies have indicated a significant impact that nutrition has on cognitive health in aging 93 — In summary, this report is the first to adopt a multivariate analysis approach to address the co-existence of nutrients and dietary compounds in the brain when investigating the relationship between nutrition and cognitive function in an aging population.

Our findings support beneficial effects of a NP higher in carotenoids potentially derived from a diet rich in fruits and vegetables similar to the MeDi and DASH diets, on lowering the risk of age-related cognitive impairment and dementia previously reported 2 , 93 , As compared to symptoms of nutritional deficiency which could be caused by an inadequate intake of one single nutrient and manifest within a short period of time, we are aware of the need to assess diet as a dietary pattern or NP in a context of complex outcomes such as age-related cognitive impairment 20 — The synergistic and cumulative effect of nutrients on a person's risk of chronic diseases have recently been highlighted in the Dietary Guidelines for Americans — and — 96 , Requests to access these datasets should be directed to elizabeth.

johnson tufts. The studies involving human participants were reviewed and approved by the University of Georgia Institutional Review Board. JT, TMS, MAJ, LWP, and EJJ designed the study.

MAJ and LWP contributed to the original design of the GCS and collection of biological samples. RV analyzed carotenoid, vitamin A, and vitamin E concentrations in all samples.

NRM and AHL analyzed fatty acid concentration in all samples. GF analyzed vitamin K concentrations in all samples. JT performed statistical analysis, wrote the paper, and had primary responsibility for final content.

All authors interpreted the data, contributed to the article, and approved the submitted version. This work was supported by Abbott Nutrition, DSM Nutritional Products, NIA 1PAG, USDA S, and USDA agreement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

van der Flier WM, Scheltens P. Epidemiology and risk factors of dementia. J Neurol Neurosurg Psychiatry. doi: CrossRef Full Text Google Scholar. van de Rest O, Berendsen AA, Haveman-Nies A, de Groot LC. Dietary patterns, cognitive decline, and dementia: a systematic review. Adv Nutr. PubMed Abstract CrossRef Full Text Google Scholar.

Trichopoulou A, Kouris-Blazos A, Wahlqvist ML, Gnardellis C, Lagiou P, Polychronopoulos E, et al. Diet and overall survival in elderly people. Zamroziewicz MK, Barbey AK. The mediterranean diet and healthy brain aging: innovations from nutritional cognitive neuroscience.

In: Farooqui T, Farooqui AA, editors. Role of the Mediterranean Diet in the Brain and Neurodegenerative Diseases. London: Academic Press But you can find this nutrient in an array of other foods as well. There is currently no recommended daily intake for lycopene. However, from the current studies, intakes between 8—21 mg per day appear to be most beneficial.

Most red and pink foods contain some lycopene. Tomatoes and foods made with tomatoes are the richest sources of this nutrient. However, when taken as a supplement, lycopene may interact with certain medications, including blood thinners and blood-pressure lowering medications One small study also found that 2 mg of daily lycopene supplements during pregnancy could increase your risk of preterm labor or low birth weight As a side note, some research reports that the beneficial effects of this nutrient may be stronger when eaten from foods rather than supplements Lycopene supplements may not be suited for everyone and do not always offer the same benefits as lycopene from foods.

In a few rare cases, eating very high amounts of lycopene-rich foods led to a skin discoloration known as lycopenodermia. In one study, the condition resulted from a man drinking 34 ounces 2 liters of tomato juice daily for several years. The skin discoloration can be reversed following a lycopene-free diet for a couple of weeks 37 , Lycopene supplements may not be suited for pregnant women and those taking certain types of medications 34 , Lycopene found in foods is generally risk-free.

However, lycopene from supplements, especially when taken in high amounts, may have some downsides. Lycopene is a powerful antioxidant with many health benefits, including sun protection, improved heart health and a lower risk of certain types of cancer.

Though it can be found as a supplement, it may be most effective when consumed from lycopene-rich foods like tomatoes and other red or pink fruits. Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available. Tomatoes are high in many nutrients, and also contain a cancer-fighting substance called lycopene.

Red vegetables, like tomatoes and bell peppers, may help reduce the risk of diabetes, osteoporosis, and high cholesterol. Watermelon is a delicious low calorie treat with numerous benefits.

Here are the top ways that watermelon can improve your health. The possible benefits of watermelon rind include better heart health, and even a better time in bed. Diet plays a major role in heart health. Eat these 17 heart-healthy foods to help keep your heart in top condition.

Guavas are packed with nutrients and have special properties that can boost your health. Here are 8 reasons to eat them, backed by science. While they're not typically able to prescribe, nutritionists can still benefits your overall health.