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Drinking Coffee Daily May Increase Your Healthspan by 2 Years, Study Finds

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Drinking three cups of coffee each day may extend healthspan by nearly two years, according to a new review published in the journal Ageing Research Reviews .

Researchers at the University of Coimbra in Portugal analyzed 85 studies worldwide examining coffee’s impact on health. The analysis indicates that three cups of coffee daily is associated with an additional 1.84 years of life spent without serious illness.

Previous studies have shown that coffee could prevent heart attacks and reduce liver disease risk. The researchers said coffee consumption also appears to lower the risk of diseases common in older adults , including heart disease, stroke, respiratory illness, some cancers, diabetes, dementia, major depression, and frailty.

This study was funded by the Institute for Scientific Information on Coffee (ISIC), a nonprofit organization that has many coffee companies as members. 

Why Might Coffee Extend Healthspan?

Antioxidants in coffee can reduce the chemical deterioration of cells and allow for the cells to recover better after being exposed to harmful effects like inflammation, according to Rodrigo Cunha, PhD , a co-author of the review and a professor of neuroscience at the University of Coimbra.

Based on the review, the researchers said that coffee’s benefits may come from its mix of over 2,000 potentially bioactive compounds. These include polyphenols , which are linked to reducing inflammation and regulating insulin production.

“While both caffeine and non-caffeine components of coffee can help extend healthy lifespan, there is still much we don’t know about the exact mechanisms behind the role these components play,” the authors wrote.

Genetic factors also influence the extent of coffee’s health benefits. Some people may experience the effects of coffee more quickly, Cunha said.

This paper can be viewed as an “accumulation of the available data on a wide variety of aging processes,” but the exact mechanism of how coffee may improve longevity is still unknown, said Shannon Kilgore, MD, a neurologist at the Veterans Affairs Health Care System in Palo Alto, California and Stanford University School of Medicine.

Does Brewing Method Matter?

A recent panel hosted by the American Medical Association (AMA) noted that unfiltered coffee like French press and espresso is associated with a small increase in LDL cholesterol , also known as the “bad” cholesterol.

This may be because filtered coffee removes much of the cafestol, a natural compound in coffee that can raise blood cholesterol levels, explained Stephen Devries, MD, a panelist and a preventive cardiologist and executive director of the educational nonprofit Gaples Institute in Chicago.

How Much Coffee Should You Drink?

Two to three cups of coffee per day seems to have some health benefits, Kilgore said. However, brewing, roasting, and coffee bean type can all affect the amount of caffeine in the coffee.

The study authors noted that the European Food Safety Authority considers up to 400 mg of caffeine per day—about five to five cups of coffee—a moderate and safe amount for most adults. The U.S. Food and Drug Administration (FDA) has the same threshold , but advises that people who are pregnant, breastfeeding, or have medical conditions affected by caffeine should consult their doctor.

Cunha said that older adults shouldn’t increase their coffee consumption to improve their health. Consuming too much caffeine could lead to symptoms like heart palpitations, high blood pressure, and anxiety.

The FDA also warns of overconsumption of caffeine, especially if you’re sensitive to it. Energy or protein bars, ice cream, chewing gum, dietary supplements and some over-the-counter medications may already have caffeine as an added ingredient.

“There’s no difference in the way your body handles or the safety between the caffeine that occurs naturally in coffee and tea, for example, and what’s added to a product, so be sure to consider all sources of caffeine in your diet,” the FDA stated.

While decaffeinated coffees and teas have less caffeine than caffeinated coffee, they still contain some amount of caffeine.

What This Means For You

A new study suggests that drinking up to three cups of coffee a day may offer health benefits, such as reducing the risk of chronic illnesses and extending healthspan by nearly two years. The FDA recommends limiting caffeine intake to 400 mg per day and being mindful of hidden caffeine in foods, drinks, and medications. If you’re pregnant, breastfeeding, or have a medical condition, consult your doctor about safe coffee consumption.

Lopes CR, Cunha RA. Impact of coffee intake on human aging: epidemiology and cellular mechanisms .  Ageing Res Rev . 2024;102:102581. doi:10.1016/j.arr.2024.102581

Kennedy OJ, Fallowfield JA, Poole R, Hayes PC, Parkes J, Roderick PJ. All coffee types decrease the risk of adverse clinical outcomes in chronic liver disease: a UK Biobank study . BMC Public Health . 2021;21(1):970. doi:10.1186/s12889-021-10991-7

Choi Y, Chang Y, Ryu S, et al. Coffee consumption and coronary artery calcium in young and middle-aged asymptomatic adults . Heart . 2015;101(9):686-691. doi:10.1136/heartjnl-2014-306663

By Fran Kritz Kritz is a healthcare reporter with a focus on health policy. She is a former staff writer for U.S. News and World Report.

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• Open access
• Published: 20 April 2021

Habitual coffee drinkers display a distinct pattern of brain functional connectivity

• Ricardo Magalhães 1 , 2 , 3 , 4   na1 ,
• Maria Picó-Pérez   ORCID: orcid.org/0000-0002-1573-2445 1 , 2 , 3   na1 ,
• Madalena Esteves 1 , 2 , 3   na1 ,
• Rita Vieira   ORCID: orcid.org/0000-0001-6762-406X 1 , 2 , 3 ,
• Teresa C. Castanho 1 , 2 , 3 ,
• Liliana Amorim 1 , 2 , 3 ,
• Mafalda Sousa 1 , 2 , 3 ,
• Ana Coelho 1 , 2 , 3 ,
• Henrique M. Fernandes 5 ,
• Joana Cabral   ORCID: orcid.org/0000-0002-6715-0826 1 , 2 , 3 , 5 ,
• Pedro S. Moreira 1 , 2 , 3 , 6 &
• Nuno Sousa   ORCID: orcid.org/0000-0002-8755-5126 1 , 2 , 3 , 7  

Molecular Psychiatry volume  26 ,  pages 6589–6598 ( 2021 ) Cite this article

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• Neuroscience

Coffee is the most widely consumed source of caffeine worldwide, partly due to the psychoactive effects of this methylxanthine. Interestingly, the effects of its chronic consumption on the brain’s intrinsic functional networks are still largely unknown. This study provides the first extended characterization of the effects of chronic coffee consumption on human brain networks. Subjects were recruited and divided into two groups: habitual coffee drinkers (CD) and non-coffee drinkers (NCD). Resting-state functional magnetic resonance imaging (fMRI) was acquired in these volunteers who were also assessed regarding stress, anxiety, and depression scores. In the neuroimaging evaluation, the CD group showed decreased functional connectivity in the somatosensory and limbic networks during resting state as assessed with independent component analysis. The CD group also showed decreased functional connectivity in a network comprising subcortical and posterior brain regions associated with somatosensory, motor, and emotional processing as assessed with network-based statistics; moreover, CD displayed longer lifetime of a functional network involving subcortical regions, the visual network and the cerebellum. Importantly, all these differences were dependent on the frequency of caffeine consumption, and were reproduced after NCD drank coffee. CD showed higher stress levels than NCD, and although no other group effects were observed in this psychological assessment, increased frequency of caffeine consumption was also associated with increased anxiety in males. In conclusion, higher consumption of coffee and caffeinated products has an impact in brain functional connectivity at rest with implications in emotionality, alertness, and readiness to action.

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Introduction.

Coffee is the most widely consumed beverage, with particular interest for human health in view of its short-term effects on attention, sleep, and memory and its long-term impact on the appearance of different diseases and on healthy span of ageing [ 1 , 2 ]. Coffee has several constituents able to impact on human health, amongst which stems caffeine, which is the most widely consumed psychostimulant in the world [ 3 ]. Despite its widespread use it is surprising to note that a thorough characterization of the chronic effects of coffee upon the human brain is still lacking. In the present work we aim to begin addressing that issue.

In the brain, caffeine acts as an antagonist of adenosine A1 and A2A receptors, leading to hyperexcitability of the central nervous system [ 3 , 4 ]. This induces acute effects in diverse domains, such as physical endurance [ 1 , 5 ], vigilance, dexterity [ 6 ], mood [ 7 , 8 ], memory [ 9 ], and cognitive function [ 1 , 8 , 10 ]. There is also evidence that coffee/caffeine intake can normalize anxiety [ 11 ], although higher doses of caffeine may be anxiogenic [ 1 , 12 ] by disrupting the HPA axis [ 13 ]. On the other hand, epidemiological and animal studies converge in concluding that coffee, caffeine and adenosine receptor antagonists attenuate the burden of neurodegenerative disorders such as Alzheimer’s [ 14 ], or psychiatric disorders such as depression [ 15 ]. Indeed, chronic antagonism of either A1 or A2 receptors seems to induce an upregulation of the former, but not the latter. The resulting altered receptor ratio may explain the shift from the acute psychomotor effects (e.g., attention, vigilance) to the longer-term actions of coffee (e.g., stress resistance, neuroprotection) effects [ 4 , 16 ].

Functional magnetic resonance imaging (fMRI) allows studying, in a noninvasive way, the function of the human brain during execution of different tasks or at rest [ 17 ]. So far, most studies using fMRI were focused on measuring the acute effects of caffeine intake in the brain. Briefly, they have reported caffeine-related increases in blood oxygenation-dependent-level (BOLD) signal in different cortical and subcortical areas during a visuomotor task [ 18 ]; an impact in working memory and perfusion in elderly subjects [ 19 , 20 ]; an increase in BOLD activation in the frontopolar and cingulate cortex during a 2-back verbal working memory task [ 21 , 22 ]; and a global caffeine-induced increase in brain entropy, possibly representing an increased processing capacity [ 23 ]. Very few studies, however, were performed to study the acute effects of caffeine in functional connectivity (FC) at rest [ 24 , 25 ]. Those few studies reveal a general trend for a caffeine-induced reduction in FC, associated with neuro-electric power fluctuations as measured through magnetoencephalography and exacerbated anticorrelations. Despite this existing literature, many aspects of the characterization of the impact of caffeine on the brain remain unexplored. Critical amongst these is the characterization of the chronic effects of habitual coffee and caffeine consumption upon the functional architecture of the brain. We are only aware of a single study that touched on this subject [ 26 ]. That work revealed an association between different habits of coffee consumption and the magnitude of BOLD signals in the visual cortex; however, it did not address possible effects on the functional connectome or resting state networks. Pursuit of the latter can present significant challenges in finding and recruiting participants with sufficient variation in consumption habits and who are willing to undergo necessary, even if short, abstinence procedures.

To tackle this gap, herein we will use whole brain approaches [ 27 , 28 , 29 ], as well as the study of brain functional dynamics [ 30 ] to compare FC and its dynamics between habitual and non-habitual coffee consumers. In addition, and because of the potential anxiogenic and HPA-disrupting role of caffeine, measures of psychological state (depression, anxiety, and stress) will also be acquired, in order to explore the potential association of habitual coffee consumption with these variables.

Subject recruitment and assessment

Participants were recruited through advertisement on the Institute’s social media, institutional e-mail, and press releases distributed among Portuguese local and national newspapers. Exclusion criteria included the presence of neurological or psychiatric disorders, habitual consumption of mind-altering substances, and the inability to undergo MRI. Two experimental groups were created according to participants’ coffee consumption habits: coffee drinkers (CD), who drank a minimum of one cup of caffeinated coffee per day; and non-coffee drinkers (NCD), who had no habits of regular consumption of coffee (less than one cup per week). Consumption of coffee as well as other caffeinated products was confirmed in a structured interview. Participants were instructed to abstain from caffeinated products for 3 h before the assessment, in order to avoid acute influence of caffeine. Fifty-six subjects were recruited (32 CD and 24 NCD). One participant from the CD group was excluded due to imaging artifacts, rendering a final sample of 31 CD and 24 NCD. Characterization of subjects was done in two (CD) or three (NCD) parts within a 3 h time-period: participants were first interviewed by a certified psychologist. This was followed by an MRI scanning session, and, in the case of the NCD, the first scanning session was followed by ingestion of coffee (Nespresso ® Ristretto, ~50 cc) before a rs-fMRI scan ~30 min thereafter. During the interview, the following data were gathered: demographic data; habits of coffee and other caffeinated products consumption; and assessment of depression, anxiety, and stress scores through the Depression, Anxiety and Stress Scales (DASS-21, [ 31 , 32 ]).

Demographic and psychological data analysis

CD and NCD groups were compared in terms of sociodemographic variables, frequency of consumption of caffeinated products, and psychological variables. Since the variables did not follow a normal distribution, nonparametric tests were applied (Wilcoxon test). Moreover, multiple regression analyses were performed, aiming to determine the association between daily consumption of caffeinated products such as coffee, tea, chocolate, etc. (0 = <1/day; 1 = 1/day; 2 = 2/day; 3 = 3 or more/day) and the psychological data measured with the DASS-21 questionnaire (controlled for sex, age, and education), independently of the groups. These analyses were performed on Matlab2020a software (The Mathworks, Inc.) and p  < 0.05 was considered the threshold for statistical significance. Linear regression representations were generated in Prism 7 software (GraphPad Software, Inc.).

MRI brain imaging

Magnetic resonance imaging scans were conducted using a Siemens Verio 3T (Siemens, Erlangen, Germany) located in Hospital de Braga (Braga, Portugal) using a 32-channel head antenna. The scanning session included as an anatomical acquisition a T1-weighted sagittal magnetization-prepared rapid acquisition with gradient echo (TE/TR = 2420/4.12 ms, FA = 9°, 1 mm 3 isometric voxel size, Field-of-View = 176 × 256 × 256 mm 3 ). The resting-state fMRI (rs-fMRI) acquisition used a multi-band echo planar imaging sequence, CMRR EPI 2D (R2016A, Center for Magnetic Resonance Research, University of Minnesota, Minnesota, USA [ 33 , 34 , 35 ]) sensitive to fluctuations in the BOLD contrast (TR/TE = 1000/27 ms, FA = 62°, 2 mm 3 isometric voxel size, 64 axial slices over an in plane matrix of 100 × 100). The rs-fMRI acquisition had a duration of 7.5 min, during which subjects were instructed to remain with their eyes closed, relaxed, and let their minds wander freely.

Preprocessing of MRI data

MRI results included in this manuscript were preprocessed using fMRIPrep 1.4.1 ([ 36 ]; RRID:SCR_016216), which is based on Nipype 1.2.0 ([ 37 , 38 ]; RRID:SCR_002502). A full description of the preprocessing pipeline can be found in the Supplementary material.

Resting-state analysis

Independent component analysis.

Resting-state network (RSN) maps were analyzed voxel-wise through a probabilistic independent component analysis (ICA) as implemented in Multivariate Exploratory Linear Optimized Decomposition into Independent Components, distributed with FSL [ 39 ]. For further details check the Supplementary material.

The RSNs FC was compared between CD and NCD groups, using a nonparametric permutation procedure implemented in the randomize tool from FSL [ 40 ]. Threshold-free cluster enhancement (TFCE) was used to detect widespread significant differences and control the family-wise error rate (FWE-R) at α  = 0.05. In total, 5000 permutations were performed.

Static functional connectomics analysis

To assess differences between the two groups in the functional connectome, the mean time series of the 268 regions of the Shen Atlas [ 41 ] were extracted. The Pearson correlation between time series, followed by Fisher r-to-Z transformation, were calculated to obtain matrices of FC for each subject. To overcome the issue of multiple comparisons induced by the large number of connections in the network, we applied the network-based statistics (NBS) approach [ 42 ]. A total of 5000 permutations were used, together with a FWE corrected network significance of 0.05. For more details check the Supplementary material.

Dynamic functional analysis

We applied the leading eigenvector dynamics analysis (LEiDA, [ 30 ]) approach to study the changes in the functional dynamics associated with habitual caffeine consumption. Instantaneous FC was calculated for each subject at each time point for all 268 regions of interest of the Shen atlas, using the time series extracted for the static analysis. To help visually identify phase locked (PL) states, the overlap between each anatomical region of each state to the 7 Yeo RSN’s [ 43 ], plus two other labels for the cerebellum and subcortical units, was calculated and anatomical units color coded in accordance to the best match. For more details check the reference paper or the Supplementary material.

Effects of acute coffee consumption and frequency of caffeine consumption

The significant findings obtained with ICA, NBS, and LEiDA were further explored, aiming to assess the effects of acute coffee consumption in NCD and of frequency of consumption of caffeinated products in both groups. The first were assessed by comparing NCD after coffee consumption with data from CD (independent sample t -test) and NCD (before coffee consumption; paired sample t -test). The second were evaluated by performing multiple regression analyses following the same approach described for the DASS-21 questionnaire.

Demographic analysis

CD and NCD groups did not differ in terms of age (range 19–57; p  = 0.28; Z  = 1.09; r  = 0.15) or number of formal years of education (range 12–25; p  = 0.07; Z  = 1.84; r  = 0.25). Frequency of consumption of caffeinated products was, as expected, higher in the CD group ( p  < 0.001; Z  = 6.17; r  = 0.83). Sex distribution was not significantly different between groups ( χ 2 (1, N  = 55) = 0.52, p  = 0.42), despite the CD group presenting a slightly higher proportion of males (41.94%) in comparison with the NCD group (33.33%). Descriptive statistics can be found in Table  1 .

Effect of habitual caffeine consumption on rs-fMRI data

Independent components analysis.

Thirty components were obtained from the probabilistic ICA of CD and NCD (before consuming coffee). Fifteen of these components were found to be representative of the most typical RSNs. A tendency toward lower FC patterns in the CD group can be seen in most of these networks (see Supplementary Fig.  1 ). Despite this, we only found significant FWE-R TFCE corrected between-group differences in two of them, namely, in the somatosensory network and the limbic network (Fig.  1 ). Regarding the somatosensory network, NCD presented a pattern of higher connectivity with the right precuneus (MNI coordinates = 30, −72, 38; 7 voxels; peak t value = 4.4). Moreover, for the limbic network, NCD had higher FC in the right insula compared to CD (MNI coordinates = 42, −12, 2; 4 voxels; peak t value = 5.09). Of note, these effects were also linearly associated with the caffeinated products’ frequency of consumption. Negative correlations were found for both right precuneus ( p  = 0.003; β  = −1.433; adjusted R 2  = 0.162; Fig.  1B ) and right insula ( p  < 0.001; β  = −2.384; adjusted R 2  = 0.267; Fig.  1B ). Detailed statistics can be found in Supplementary Table  1 .

A Sagittal, coronal, and axial view of the clusters showing significant between-group differences in the connectivity between the somatosensory network and the right precuneus (top) and the limbic network and the right insula (bottom). The FWE-R TFCE corrected clusters are shown in dark blue overlaid over a more extended non-significant after multiple comparison correction cluster in hot color scale scheme, for visualization purposes. B Associations of frequency of consumption of caffeinated beverages with the mean FC of the right precuneus and the right insula. C Scatter plots showing the mean FC of the right precuneus and the right insula for the NCD before drinking coffee (NCD), the NCD after drinking coffee (NCD pos), and the CD.

Importantly, the group differences described were reduced after NCD drank coffee (see Fig.  1C ; somatosensory network: pre vs post NCD t value = 1.86, p  = 0.075, post NCD vs CD t value = −2.89, p  = 0.006; limbic network: pre vs post NCD t value = 3.88, p  < 0.001, post NCD vs CD t value = −1.46, p  = 0.15). This points to a potential causality link between coffee drinking and the above-described changes in lower connectivity in the somatosensory and in the limbic networks.

Connectomics analysis

From the connectomics analysis done using NBS, a single network of significantly higher connectivity was found in the NCD group (pre-coffee) between the thresholds of 0.005 and 0.0005 (for statistics of all thresholds see Supplementary Table  2 ). For ease of visualization, we present only the results found at the highest significant threshold of p  = 0.0005 ( t (threshold) = 3.71, df = 54, p (network) = 0.043, Hedge’s g  = 1.08 (large effect size), 24 nodes, 46 edges; Fig.  2A ). The full list of nodes with significant different edges between groups across all thresholds can be found in Supplementary Table  3 . Of these we highlight the Thalamus (nodes #262 and #126), the Cerebellum (left anterior Culmen #245 and bilateral Tonsils #238 and #119), the right Postcentral Gyrus (#33), the left Middle Temporal Gyrus (#197), the left Precentral Gyrus (#160), and the bilateral Caudate (#260 and #122) and Putamen (#124 and #261) as having the most strongly affected connections within the network.

A Sagittal, coronal, and axial view of the network with nodes and edges colored in red–yellow color scheme representing the statistical t value of the difference between groups. B Scatter plot of the mean FC within the significant network for each experimental group. C Associations of frequency of consumption of caffeinated beverages with the mean FC of the network found in NBS.

When observing the average network connectivity from this network, NCD post-coffee drink displayed a significant reduction in connectivity (Fig.  2B ), leading to a profile more similar to CD ( p  = 0.037, t  = 2.13, df = 54) than to NCD pre-coffee drink ( p  = 1.3 × 10 −7 , t  = 7.4, df = 23). NBS mean FC was negatively associated with frequency of caffeine consumption ( p  < 0.001; β  = −0.101; adjusted R 2  = 0.506; Fig.  2C ). Detailed statistics can be found in Supplementary Table  1 .

From the dynamic FC analysis, one functional subsystem (Fig.  3A , PL state 4) was found to last significantly longer in CD (Fig.  3B , 17.95 ± 18.32 s) compared to pre-coffee NCD (8.95 ± 6.13 s) surviving correction for multiple comparisons with a corrected p  = 0.038 and a medium effect size with Hedge’s g  = 0.62. No BOLD phase-locking state was found to significantly differ in terms of probability of occurrence (see Supplementary Table  4 for all p values for all partition models).

A sagittal and axial views representing the state anatomical areas of each phase locked (PL) state. B Bar plot representing the group differences between coffee and non-coffee drinkers. Differences of p  < 0.05 are indicated in red, while multiple comparison surviving effects are indicated in green. C Associations of frequency of consumption of caffeinated beverages with the average duration (in seconds) of PL state 4. D Bar plot of the probability of state 4 for the CD, NCD, and NCD post caffeine consumption groups. E Life time of state 4 for the CD, NCD, and NCD post caffeine consumption groups. F Colored labels used to match each anatomical area of the PL states to different resting state networks.

This BOLD phase-locking state, corresponding to the fourth most probable state when partitioning the data into nine states, comprises a large number of nodes in the cerebellum, visual network as well as several subcortical nodes such as the bilateral thalamus and parahippocampal gyrus (mapped and color coded through the reference shown in Fig.  3F ). While this was the only result that survived correction for multiple comparisons, it is relevant to note that the equivalent LEiDA state for k  = 10 is just below the threshold ( p  = 0.051, Supplementary Table  4 and Supplementary Figs.  2 and 3 ). Furthermore, LEiDA lifetime results were positively correlated with frequency of caffeine consumption ( p  = 0.012; β  = 2.176; adjusted R 2  = 0.083; Fig.  3C ).

After drinking coffee, both the lifetime and the probability of this state in NCD became closer to the values observed in CD, with the probability not being significantly different from CD ( p  = 0.5, t  = 0.67, df = 54), while being significantly higher than NCD pre-coffee ( p  = 0.037, t  = 2.31, df = 23, Fig.  3D ). For the life time of state 4, post-coffee drink NCD were not significantly different from CD ( p  = 0.177, t  = 1.37, df = 54) nor the pre-drink NCD ( p  = 0.107, t  = 1.68, df = 23, Fig.  3E ). All results across the different k’ s can be found in Supplementary Figs.  2 and 3 and Supplementary Table  4 .

Effect of habitual caffeine consumption on psychological data

The association between coffee consumption and stress, anxiety, and depression (DASS-21) was assessed. When comparing CD and NCD groups, only stress was significantly different between groups (stress— p  = 0.025; Z  = 2.237; r  = 0.307; anxiety— p  = 0.851; Z  = −0.188; r  = −0.026; depression— p  = 0.085; Z  = 1.724; r  = 0.237), with CD showing higher levels of stress than NCD (median (Med) = 6.0; interquartile range (IQR) = 6.0 vs Med = 4.0; IQR = 4.0, respectively). Of notice, particular items of the DASS-21 Stress subscale that can be related to arousal were increased in CD. Items #1 and #12, which measure difficulty to relax, presented statistically significant differences ( p  = 0.007, Mann–Whitney test), while item #8, that relates to nervous arousal, presented a trend in the same direction ( p  = 0.083). Interestingly, item #7 (Anxiety subscale), that is associated with skeletal musculature, despite not achieving a statistically significant difference between groups, tended to be lower in CD ( p  = 0.113), suggesting a segregation between the motor and arousal loops.

When assessing the effects of frequency of caffeine consumption in self-reported variables (controlling for sex, age, and education), the positive correlation with stress was maintained ( p  = 0.004; β  = 1.292; adjusted R 2  = 0.135; Fig.  4A ). Moreover, a sex by anxiety interaction was found ( p  = 0.023; β  = 0.683; adjusted R 2  = 0.085; Fig.  4B ), which seems to be driven by a positive correlation in males. No significant effects were found for the depression subscale ( p  = 0.128; β  = 0.450; adjusted R 2  = 0.108; Fig.  4C ). Detailed statistics can be found in Supplementary Table  1 .

Associations of frequency of consumption of caffeinated products with the DASS-21 subscales of stress ( A ) and anxiety ( B ), and non-significant association with the depression subscale ( C ).

Herein we describe for the first time the effects of habitual coffee consumption on the human brain networks. We show that habitual CD have different patterns of FC in comparison with NCD. Our rs-fMRI analysis revealed decreased FC of the somatosensory and limbic networks in CD that correlated with the frequency of consumption of caffeinated products. Such changes were replicated in NCD after a single coffee, suggesting possible causality between coffee intake and altered patterns of brain network connectivity. Previous studies have described a reduction of similar RSN connectivity after acute caffeine ingestion [ 25 , 44 ].

Decreased FC in somatosensory and related networks in CD likely represents a more efficient and beneficial pattern of connections with respect to motor control and alertness; importantly this fits our findings of trends of increased scores in CD in the specific items of the DASS-21 scale that measure these dimensions. The other network impacted by coffee intake was the limbic network, which is involved in processing the sensory input from the external and internal environment which, by modulating memory and motivation, determine emotional, autonomic, motor, and cognitive responses [ 45 ]. A previous resting-state PET study showed reduced metabolic activity in components of this network after caffeine ingestion [ 18 ] and a study using a hedonic fMRI task showed decreased activation in neuronal areas associated with memory and reward [ 46 ] in caffeine consumers compared to non-consumers; the present FC data are consistent with those reports.

Analysis of the global functional connectome using NBS revealed a network impacted by the habitual consumption of caffeine. This widespread network of reduced FC comprised cerebellar, subcortical (striatal and thalamic), and motor cortex regions, partially matching previously reported effects of acute caffeine ingestion [ 24 , 25 ]. Interestingly, there is a clear bilateral involvement of striatal nodes and of the thalamus which, respectively, have the highest densities of A2A and A1 receptors in the brain [ 47 , 48 ]. The action of caffeine in these regions has an influence on cortico-striatal-thalamic and cerebellar-thalamocortical loops that are relevant for a variety of neuronal processes. Thus, the observed decrease in FC at rest in this network in regular caffeine-ingesting individuals reveals greater segregation of these areas with less inter-regional dependencies, favoring greater efficiency within these loops. It is relevant to note here that, even though A1 and A2A receptors are thought to mediate differential actions [ 49 ], similar effects were observed in both loops. This likely reflects the fact that fMRI provides proxy aggregate measurements of functional connections among a network of brain areas.

A previous study reported that caffeine increases brain entropy, indicating higher information processing capacity across the cerebral cortex [ 23 ]. Our LEiDA analysis revealed a dynamic state involving several cerebellar and subcortical areas, with a longer average lifetime in habitual CD. This network comprises several nodes, including the cerebellum, thalamus, and parahipocampal, lingual, and inferior occipital gyri which are relevant in the context of caffeine consumption—caffeine is known to decrease mind wandering [ 50 ] and to increase attention, alertness, and arousal [ 51 ]. In fact, the nodes implicated in this network are linked by visual processing; among these, the thalamus is critical for distributing cognitive control [ 52 ]. The lingual and inferior occipital gyrus are also implicated in visual processing, while the parahippocampus is involved in memory encoding and retrieval [ 20 , 21 ]; the latter may explain why caffeine reportedly facilitates memory processes [ 9 ]. Lastly, evidence of strong rsFC between the cerebellum, known to be also implicated in sensory processing [ 53 ] and a number of sensorial cortices [ 54 ], explains the observed increased visual alertness/attention and readiness to sensorial perception among CD individuals. While similar findings have been previously reported [ 6 ], only one other study assessed habitual CD using MRI, and did not characterize changes in FC [ 26 ]. Importantly, similarly to the other neuroimaging findings, a common pattern of connectivity dynamics was found in CD individuals and NCD subjects who drank a single coffee before scanning.

In order to provide a link with other neuropsychologic dimensions, we also assessed our subjects in the DASS-21. Interestingly, we observed habitual CD to display increased levels of stress; there was a clear positive association between the indices of stress and the amount of consumption of caffeinated drinks. Interestingly, items of the DASS-21 sub-score that showed greater variance between CD vs NCD were those related with difficulty to relax (items #1 and #12), and those related to nervous arousal (item #8), consistent with the common attribution of alertness and arousal to coffee intake. It also deserves to be mentioned that, despite the display of a higher anxiety among CD (particularly in males), there was a decrease in DASS-21 item (#7) which matches the effects on the skeletal muscles in CD; this, in turn, fits the findings of better segregation of the above-described loops. The present results extend previous studies that described an association between coffee/caffeine consumption and stress and anxiety [ 1 , 13 , 16 , 55 ] and sex [ 13 , 16 ]. It is important to note, however, that causality cannot be inferred from our study design. Our results are open to two interpretations: higher coffee/caffeine consumption leads to increased stress and anxiety; or, alternatively, higher stress and anxiety induce higher coffee/caffeine consumption. Moreover, given that resting-state studies using stress and anxiety samples have shown both decreases and increases in FC [ 56 , 57 , 58 ], the possibility that coffee/caffeine consumption elicits decreases in FC or compensates for FC beyond a certain threshold, must also be considered. While the first possibility is in line with studies showing increased anxiety upon both acute caffeine administration in humans [ 1 , 12 ] and prolonged ingestion in rodents [ 59 ] reports that greater caffeine consumption under periods of stress may help maintain synaptic homeostasis [ 60 ] as well as prevent mood disorders warrant further study in future.

The methodologies applied in the present study do not allow us to draw precise relationships between the psychological and neuroimaging results and the dosage and metabolism of caffeine among individual subjects. To study the individual responses to the acute and chronic effects of caffeinated product intake would be a complex undertaking, requiring subjects to adapt their daily habits and strict abstinence regimens. Based on our experience, recruitment of subjects for a properly balanced study is also difficult since NCD subjects are insufficiently motivated to engage in studies on the actions of caffeine. Nevertheless, we are currently developing alternative strategies that would allow us to deliver calibrated doses of caffeine during fMRI scanning sessions to better discriminate its effects from other factors (e.g., stress). Our future work will also examine inter-individual differences in response to caffeine consumption, the subjective experience of coffee consumption, as well as the influence of additional factors as the consumption of alcohol and tobacco. Despite such gaps, the data presented here represent a contribution to the knowledge of the “caffeinated brain” and how these changes underlie the behavioral effects triggered by coffee intake, with implications for physiological and pathological conditions.

Code availability

In-house scripts used in the NBS analysis are fully available online at open science framework website ( https://osf.io/qepc8/ ) and LEiDA scripts at github ( https://github.com/juanitacabral/LEiDA ).

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This study was funded by the Institute for the Scientific Information on Coffee (ISIC) (ISIC_2017_NS); ISIC did not influence the experimental design or data analysis/interpretation. The laboratory was also supported by the project NORTE‐01‐0145‐FEDER000013 through the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). RM, MP-P, and ME were supported by post-doctoral grants from the project ISIC_2017_NS. PSM was supported by a fellowship grant from the Fundação para a Ciência e a Tecnologia (FCT; grant number PDE/BDE/113601/2015) from the PhD-iHES program. RV was supported by a research fellowship of the project funded by FCT (UMINHO/BI/340/2018). AC was supported by a scholarship from the project NORTE-08-5639-FSE-000041 (NORTE 2020; UMINHO/BD/51/2017).

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These authors contributed equally: Ricardo Magalhães, Maria Picó-Pérez, Madalena Esteves

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Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, Braga, Portugal

Ricardo Magalhães, Maria Picó-Pérez, Madalena Esteves, Rita Vieira, Teresa C. Castanho, Liliana Amorim, Mafalda Sousa, Ana Coelho, Joana Cabral, Pedro S. Moreira & Nuno Sousa

ICVS/3B’s, PT Government Associate Laboratory, Braga/Guimarães, Portugal

Clinical Academic Center - Braga, Braga, Portugal

NeuroSpin, CEA, CNRS, Paris-Saclay University, Gif-sur-Yvette, France

Ricardo Magalhães

Center for Music in the Brain, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

Henrique M. Fernandes & Joana Cabral

Psychological Neuroscience Lab, CIPsi, School of Psychology, University of Minho, Braga, Portugal

Pedro S. Moreira

P5 Medical Center, Braga, Portugal

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Magalhães, R., Picó-Pérez, M., Esteves, M. et al. Habitual coffee drinkers display a distinct pattern of brain functional connectivity. Mol Psychiatry 26 , 6589–6598 (2021). https://doi.org/10.1038/s41380-021-01075-4

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Brain scans of coffee drinkers suggest there's more to feeling alert than just the caffeine

Many coffee drinkers will tell you there's something about that morning cup that other sources of caffeine just can't match.

Researchers in Portugal recently set out to investigate that idea: Is caffeine solely responsible for making people feel more alert, or do other parts of the morning ritual — coffee's smell or taste, perhaps — trigger that energetic feeling?

"If you listen to these individuals, they typically say that they need to have coffee in the morning to get ready. We wanted to understand the brain mechanisms and functional connectivity pattern that would justify this claim," said Nuno Sousa, one of the study's authors and a professor at the University of Minho's School of Medicine in Portugal.

The researchers recruited 83 people who drank at least one cup of coffee a day to undergo MRI scans so they could observe the participants' brain activity.

Of that total, 47 people were scanned before drinking their morning cup of coffee, then again 30 minutes after they had a cup. The 36 others were simply given caffeine diluted in hot water — no coffee — and underwent the same types of MRI scans before and after they consumed the beverage.

The results, published last week in the journal Frontiers in Behavioral Neuroscience, suggest that, indeed, certain changes in brain activity were attributable only to coffee, while others were attributable to caffeine, as well.

The scans revealed that both groups — those who consumed caffeine and those who drank coffee — had decreased activity afterward in a part of the brain that puts people in a resting state. That indicated that people were more ready to start their days and engage with others after consuming either beverage. Decades of research has already shown that caffeine, a psychostimulant , can help people feel more aroused and alert.

However, the MRI scans showed that drinking coffee increased activity in parts of the brain involved in short-term memory, attention and focus, whereas ingesting caffeine on its own did not.

The researchers theorized that the sight, smell or taste of coffee may help people feel alert, regardless of the caffeine content.

"The pleasure that is given to an individual that likes coffee in the morning, that actually is part of almost a ritual that really is also important for that individual to feel that 'I'm ready for the day,'" Sousa said.

He added that people who don't regularly drink coffee may not experience the same effect.

Mark Mattson, an adjunct professor of neuroscience at Johns Hopkins University School of Medicine who wasn't involved in the research, said the findings weren't surprising, since people form associations with particular sensory experiences over time, which in turn can influence their future reactions.

"It kind of makes sense, right? Coffee has taste and smell, so when you drink coffee, you're activating brain regions that are involved in the perception of the taste of the coffee, the perception of the smell," Mattson said.

Dr. Uma Naidoo, a nutritional psychiatrist at Harvard Medical School, said the sight of coffee may trigger positive memories or make a person believe they're about to feel more awake.

"The visual impact of coffee is powerful," she said. "It could be like, 'Oh, I think there’s something that gives me energy now. I’m going to have something that gives me that second wind I need at work or to study.'"

That's different from a placebo effect, she added, since the coffee is still inducing a physical, and perhaps emotional, response.

All three researchers said it's also possible that the natural chemicals found in coffee may have independent effects on brain activity, apart from those of caffeine. A group of chemicals in coffee called epicatechins, for instance, has been shown to improve memory in animal studies .

Sousa said the goal of the study is not to influence anyone's coffee consumption habits.

"We are not saying that coffee is good or coffee is bad," he said.

Mattson also pointed out that the study comes with several limitations. For one, the MRI scans measured blood flow, but caffeine can restrict blood flow, so the scans may not give a clear picture of its impact on brain activity. Mattson also noted that the study didn't include people who drank decaf coffee, which might have helped distinguish the effects of coffee versus caffeine on the brain.

Naidoo, meanwhile, highlighted that most of the study participants were women, so there could be sex-based differences in how people's brains respond to coffee.

But one point on which the researchers agreed is that coffee is a healthier way to consume caffeine than energy drinks or soda.

"It has caffeine, but it also is very rich in antioxidants and some polyphenols," Naidoo said, referring to natural compounds that may lower blood pressure, destroy cancer cells and protect against diabetes by improving metabolism.

"There’s also another substance called trigonelline that gives coffee the aroma, the taste, that bitterness, but it also has antibacterial, antiviral properties," Naidoo said.

Aria Bendix is the breaking health reporter for NBC News Digital.

The Institute for Scientific Information on Coffee (ISIC) is a not-for-profit organisation

New review highlights that daily coffee consumption can add up to two extra years of healthy aging to your life, european dietitians’ perspectives on coffee consumption, what’s new, new research reveals a potential mechanism for how coffee may reduce the risk of type 2 diabetes.

A new study published in Clinical Nutrition and funded by the Institute for Scientific Information on Coffee (ISIC) has found that coffee consumption may help reduce the risk of type 2 diabetes (T2D), mediated by differences in inflammatory biomarkers in the body. The research assessed the underlying mechanisms by which coffee consumption may help to reduce T2D risk, with an additional cup of coffee per day being associated with a 4-6% lower risk.

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3-4 cups of coffee per day is associated with an approximate 25% lower risk of developing type 2 diabetes.

Coffee can used as an ergogenic aid and can improve performance in endurance cycling and running.

Drinking coffee can stimulate digestion as well as reducing risk of gallstones and certain liver diseases, such as pancreatitis.

2-3 cups of coffee daily is associated with a 10-15% reduced risk of developing coronary heart disease, heart failure or a heart rhythm problem.

Health conditions

Bone health.

Incidence of osteoporotic fractures between and within countries vary largely, partly related to economic prosperity. The number of osteoporotic fractures is also rapidly rising in many countries.

According to 2020 data from the World Health Organization (WHO), cancer causes 20% of all deaths in Europe.

Cardiovascular health

CVD remains the leading cause of mortality and a major cause of morbidity in Europe. Lifestyles choices are the biggest risk factors associated with the risk of developing CVD and for CVD mortality.

GI function

Functional gastrointestinal disorders (FGIDs), of varying symptoms and severity, are a growing burden on populations and healthcare systems. Often a causal link cannot be isolated, requiring a number of diagnostic procedures and treatment.

Gallstones are small stones, usually made of cholesterol, that form in the gallbladder. Whilst gallstones are quite common, the number of deaths are significantly decreasing.

Liver function

The European Association for the Study of the Liver estimates that approximately 29 million people in the European Union suffer from a chronic liver condition.

Neurodegenerative disorders

Cognitive functions remain relatively stable until an individual reaches approximately 60 years old, at which point they tend to slow down, particularly between 60 and 80 years.

Type 2 diabetes

Type 1 and 2 diabetes are significant public health concerns across the globe, particularly in low and middle-income countries.

Coffee and the senses

The sensory experience when consuming a cup of coffee is one of the key aspects of the beverage, providing unique aromas, tastes and flavours.

Fluid balance

The study of the effect of coffee on fluid balance can be split into two distinct areas: caffeine intake in the general population and caffeine intake specifically during exercise.

Life expectancy

Life expectancy is an important demographic statistic that can be used to compare the health status of different population groups.

Mental performance

The association between caffeine consumption and an increase in alertness and performance has been well documented.

It is widely accepted that any effects of coffee consumption on reproductive health are likely to be linked to caffeine rather than to coffee consumption per se.

Sports performance

Research suggests that caffeine may help to improve physical performance during both endurance and high-intensity exercise.

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Studies on coffee consumption: New biomarker proposed

N-methylpyridinium could be used as a new, practical food biomarker.

In order to record coffee consumption in nutrition and health studies, researchers usually rely on self-reporting by participants. However, this is not always reliable. It would therefore be desirable to conduct additional studies to objectively verify individual consumption using biomarkers. A research team led by the Leibniz Institute for Food Systems Biology at the Technical University of Munich has now validated the suitability of a specific roasted coffee compound and proposes it as a new, practical food biomarker.

Millions of people around the world drink coffee every day. The beverage contains a large number of bioactive substances, and its health effects on the human metabolism are therefore frequently subjects of scientific studies. In many of these studies, however, the data on coffee consumption is largely based on self-reporting by the participants and is therefore not always accurate. This can affect the scientific validity of nutritional studies.

Biomarkers could provide a remedy

Reliable biomarkers could remedy this problem by using biological samples to objectively distinguish between coffee drinkers and non-coffee drinkers. "So far, however, only a few substances are known that could be used as coffee markers," says principal investigator Roman Lang from the Leibniz Institute. "However, these are not yet sufficiently validated or available in sufficient quantities to serve as reference substances for comparative measurements in nutritional studies," he continues.

The research team, which also includes the nutritional physician Thomas Skurk and first author Beate Brandl from the ZIEL -- Institute for Food & Health at the Technical University of Munich, has therefore comprehensively validated the roast coffee compound N -methylpyridinium as one such biomarker candidate for its suitability. Researchers at the Technical University of Munich first proposed the substance as a biomarker candidate in 2011 as part of a pilot study.

Data from over 460 people analyzed

As part of the scientific validation, the team analyzed existing literature data. It also analyzed urine, blood and plasma samples from more than 460 people from Freising and Nuremberg who had participated in a nutrition study conducted by the BMBF-funded enable cluster.

As the study shows, N -methylpyridinium is a compound that is specific to roasted Arabica and Robusta coffee. The substance is chemically very stable and its absorption into the organism is concentration-dependent. The substance can also be easily and reproducibly detected in various body fluids after coffee consumption, before leaving the body unchanged in the urine within a few hours to days.

Roman Lang, who heads the Biosystems Chemistry & Human Metabolism research group at the Leibniz Institute, explains: "As we have shown, N -methylpyridinium fulfills all the criteria that science demands of a biomarker to control food intake. Even if we cannot draw direct conclusions about the amount of coffee consumed due to various factors, the roasting substance is still suitable as a marker. This is because it allows us to distinguish objectively and practically between people who have drunk coffee and those who have not. We therefore propose it as a reliable qualitative biomarker for coffee consumption."

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Materials provided by Leibniz-Institut für Lebensmittel-Systembiologie an der TU München . Note: Content may be edited for style and length.

Journal Reference :

• Beate Brandl, Coline Czech, Susanne I. Wudy, Anja Beusch, Hans Hauner, Thomas Skurk, Roman Lang. Validation of N-Methylpyridinium as a Feasible Biomarker for Roasted Coffee Intake . Beverages , 2024; 10 (1): 12 DOI: 10.3390/beverages10010012

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