Many ‘antidepressant’ drugs on the market today, are prescribed with the intention of increasing levels of active serotonin – the so called ‘happiness hormone’ – circulating in the brain. Unfortunately (and not for biologically inexplicable reasons) they have been associated with increased suicide rates among users. Coffee is protective.
“The FDA admitted in 2007 that SSRIs [selective serotonin reuptake inhibitors] can cause madness at all ages and that the drugs are very dangerous…All patients being treated with antidepressants…should be…observed closely for clinical worsening, suicidality, and unusual changes in behavior…The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported…” (Adshead G, 2017)
Coffee seems to act in what could reasonably be described as the opposite direction – improving overall metabolic function, lowering exposure to excess serotonin – and this is likely an important part of the reason why regular coffee drinkers are known to have a reduced incidence of suicide.
“…suicide risk…decreased in a dose-dependent manner with increasing consumption of coffee. As compared with non-coffee drinkers…suicide was 45% lower among individuals who consumed 2–3 cups of coffee per day, and 53% lower among individual consuming ≥4 cups of coffee per day.” (Lucas M, et al., 2014)
“We conducted a 10-year follow-up study (1980 to 1990) in an ongoing cohort of 86 626 US female registered nurses aged 34 to 59 years…A strong inverse relationship was similarly found for caffeine intake from all sources and risk of suicide…The data suggest a strong inverse association between coffee intake and risk of suicide…” (Kawachi I, et al., 1996)
“Restraint stress…caused a marked increase in dopamine and serotonin (5-HT) levels in the hippocampus…Pretreatment with 33 mg/kg coffee or 1.7 mg/kg caffeine reduced…restraint-induced increase in the neurotransmitters, especially 5-HT…” (Yamato T, et al., 2002)
Rising exposure to serotonin isn’t all that it’s cracked up to be. Although serotonin does have a basic physiological role, and is involved in the defense against excessive stress and starvation situations, chronically and systemically high serotonin exposure is known to promote inflammation and disease.
Serotonin is closely tied to the regulation of emotion, and excess serotonin has been demonstrated to interfere with thyroid function, reducing metabolic rate, impeding brain function, thereby potentially promoting symptoms of anxiety and depression, including learned helplessness and despair.
Much like the physiological state of hibernation – which occurs in the presence of rising levels of serotonin (as well as suppressed body temperature and brain function) – many of the features of depression go hand in hand with an under performing thyroid energy metabolism.
“Patients affected by subclinical hypothyroidism had a prevalence of depressive symptoms of 63.4%…This study underlines a strong association between subclinical hypothyroidism and depressive symptoms, which could have some important diagnostic and therapeutic implications in the clinical practice.” (Demartini B, et al., 2014)
In both of these stressful scenarios (i.e. hibernation and depression) there is a shift towards the use of fat as fuel for the cells (away from the metabolism of glucose), similar in many ways to the physiological conditions which lead to blood sugar dysregulation, insulin resistance and diabetes.
In fact, plenty of good evidence exists which shows a relationship between emotional stress, anxiety and diabetes, and there is no shortage of biologically rational explanations for why this makes sense.
“Chronically high anxious arousal and inflammation increase one’s risk of developing type 2 diabetes…Individuals with low inhibition were more likely to have diabetes than those with high inhibition due to the serial pathway from high anxious arousal to IL-6…” (Murdock KW, et al., 2016)
One good rationale is that stress and low blood sugar interfere with thyroid function and energy metabolism, promoting the release of many inflammatory stress substances (such as cortisol, serotonin, nitric oxide and estrogen) implicated in the progression of degenerative conditions including depression and diabetes.
This kind of metabolically suppressed state is more likely to become a persistent or chronic issue, as fat stores become increasingly polyunsaturated. This is due in large part to the many inflammatory, immunosuppressive and thyroid interfering features of the polyunsaturated fats (PUFAs), which are released as free fatty acids into the bloodstream, in larger amounts under conditions of stress.
As well as having powerful anti-thyroid and inflammatory effects, the breakdown products of the PUFAs can increase the harm potential of cortisol, serotonin, nitric oxide and estrogen, encouraging greater interference with metabolic energy production, worsening issues related to proper blood sugar regulation.
Depression and anxiety have been shown to be the result of a hypometabolic state, exacerbated by oxidative stress (resulting from the breakdown products of PUFAs), and directly associated with symptoms of blood sugar dysregulation and diabetes.
Inflammation is well known to be a factor involved in the progression of mood dysregulation and suicidal thinking and behavior, and caffeine protects against inflammation and oxidative stress.
“…there is a growing body of evidence that inflammation, as manifested by increased levels of pro‐inflammatory cytokines and inflammatory metabolites, is present in patients with suicidal behaviour and ideation…” (Brundin L, et al., 2015)
Stress and the breakdown of PUFAs, increases exposure to bacterial endotoxin, and endotoxin (LPS) directly causes inflammation, and interferes with oxidative energy production. Endotoxin is well known to be involved in the progression of metabolic disease, and has been studied in relation to depression and anxiety. Caffeine protects against the inflammatory stress promoting effects of endotoxin.
“In LPS-exposed rats IL-1β and CD68 cell counts both increased at p8 compared to NS controls. These increases in proinflammatory markers were no longer present in caffeinetreated LPS-exposed pups…suggesting a protective effect of caffeine on respiratory function via an anti-inflammatory mechanism.” (Köroğlu OA, et al., 2014)
It has been demonstrated that the stress hormone cortisol, more commonly promotes depression in men, with estrogen being a stronger driver of depression in women. Experimental evidence continues to show that depression and anxiety is actually a high serotonin state (which goes hand in hand with rising cortisol and estrogen), and caffeine has been shown to reduce serotonin levels, including brain serotonin.
“Corticosteroids may play an important role in the relationship between stress, mood changes and perhaps suicidal behavior by interacting with 5-HT1A receptors. Abnormalities in the HPA axis in response to increased levels of stress are found to be associated with a dysregulation in the serotonergic system, both in subjects with mood disorders and those who engage in suicidal behavior.” (Pompili M, et al., 2010)
Serotonin promotes cortisol and estrogen, and estrogen induces nitric oxide production. Nitric oxide has also been demonstrated to be involved in the progression of anxiety and depression, and is associated with suicide. Caffeine and some other things found in coffee can lower nitric oxide.
“In recent studies, it has been shown that kahweol, coffee-specific diterpene, exhibit chemoprotective effects…The nitrite production induced by LPS was markedly reduced in a dose-dependent manner…kahweol suppressed the expression of iNOS protein and iNOS mRNA.” (Kim JY, et al., 2004)
Coffee is known to stimulate thyroid function, as well as having been shown to suppress estrogen and cortisol levels, and so it can be seen to be helping with depression and related mood issues, on a variety of metabolic fronts.
“Coffee extract blocked 11beta-HSD1-dependent cortisol formation…We suggest that at least part of the anti-diabetic effects of coffee consumption is due to inhibition of 11beta-HSD1-dependent glucocorticoid reactivation.” (Atanasov AG, et al., 2006)
An increase in dopamine relative to serotonin is another factor which it has been suggested has antidepressant significance, and there is evidence that caffeine (whilst lowering serotonin) also increases dopamine.
Caffeine assists with the production of the protective hormones pregnenolone and progesterone, and both these substances are protective against depression and anxiety, as well as other mood disorders such as bipolar, schizophrenia and PTSD. Low pregnenolone production is associated with suicide.
“The study showed that pregnenolone was significantly decreased in the parietal cortex in the combined group of patients with schizophrenia or bipolar disorder who died by suicide compared with patients with these disorders who died of other causes.” (Youssef NA, et al., 2015)
Caffeine is a non-selective adenosine antagonist, increases cAMP by inhibition of PDE-4, promotes GABA and glutathione, and inhibits parathyroid hormone, and these are some other factors involved in protection against mood dysregulation, and various other inflammatory metabolic conditions.
Coffee and caffeine (much like improved thyroid function) increase body temperature, and whole body hyperthermia, is something that has been used successfully to treat depression.
“The thermic effect of the meal was significantly greater after coffee than after decaffeinated coffee… caffeine/coffee stimulates the metabolic rate in both control and obese individuals…” (Acheson KJ, et al., 1980)
“The internal temperature started to increase after both treatments, but became slightly different 2 h after caffeine consumption. Mean skin temperature after caffeine consumption increased, and became significantly different compared to the control treatment after 90 min…” (Koot P, Deurenberg P. 1995)
Caffeine increases metabolic rate and promotes the production of mitochondria, and it is not by coincidence that mitochondrial dysfunction is involved in the progression of mood dysregulation. As with any substance that stimulates metabolism however, caffeine increases the amount of glucose which is able to be used by the cells, and so it requires fuel.
“From our data we gather that caffeine stimulates metabolism and favorable mitochondrial production…Our findings support the advertised metabolic benefits of caffeine, making it a potential contributor in humanity’s struggle against obesity.” (Vaughan RA, et al., 2012)
When sufficient sugar is not consumed with coffee (especially if glycogen stores are already low as a result of stress) this can result in an increase in the release of adrenaline and cortisol (as a means to sourcing out an alternative fuel supply), turning what is able to be a mood stabilizing (as well as enhancing) disease protective food, into something potentially stress increasing and anxiety promoting.
As well as stimulating cortisol and adrenaline, the consumption of too much coffee (relative to energy availability), can lead to a rise in other stress substances like serotonin, nitric oxide and estrogen, and can also promote the release of the polyunsaturated free fatty acids, potentially worsening stress and inflammation.
In this sense, consuming lots of coffee without the accompaniment of plenty of fuel, can create the impression that coffee per se is harmful, and responsible for a worsening of metabolic issues.
Many of the experiments showing negative aspects of coffee or caffeine, have been designed without taking these factors into consideration, and often use unnaturally high doses, leading to results which are highly misleading and unhelpful.
I’m not a doctor or a scientist, and none of this is intended as (or as a replacement for) medical advice. Nor is it intended to oversimplify what can be complex, multi-faceted issues. I’m just pointing out some of the ways science has demonstrated that regular consumption of coffee (and some other things), can be protective against inflammatory conditions, including depression, liver disease, diabetes, MS, Parkinson’s, cardiovascular disease and cancer.
“High versus low coffee consumption was associated with a lower risk of prostate cancer, endometrial cancer, melanoma, oral cancer, leukaemia, non-melanoma skin cancer, and liver cancer. For prostate, endometrial, melanoma, and liver cancer there were also significant linear dose-response relations indicating benefit.” (R Poole, et al., 2017)
The ability of coffee or caffeine to protect against depression and suicide, is, I believe, directly connected to the liver protective (and healing) impact of regular coffee consumption, as a well functioning liver is important for proper thyroid function and for protection against systemic exposure to inflammatory stress substances, including estrogen and endotoxin. Sufficient intake of sugar and protein are fundamental to good liver function.
A diet avoiding PUFAs and limiting intake of difficult to digest grains, seeds, nuts, beans and too much under cooked vegetable matter, with sufficient protein from milk, cheese and gelatin, and plenty of sugar from sweet fruits, fruit juice, white sugar and honey, is one possible way to improve liver function, lower inflammation, and help to get the benefits from regular coffee (and other caffeinated drink) consumption.
Some other things that have been shown to help improve metabolism, liver function and mood issues, include aspirin, niacinamide, glycine, K2, methylene blue, thiamine, vitamin E, taurine, activated charcoal and cyproheptadine.
Ironically, sensitivity to coffee has been demonstrated to be an effective measure of liver damage.
Do you have enough sugar with your coffee, or in your diet?
For people who are super sensitive to the effects of coffee, one thing that potentially helps improve the ability to handle gradually increasing quantities, is to start by introducing it in very small amounts, in combination with milk and sugar, or with meals.
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FEBS Lett. 2006 Jul 24;580(17):4081-5. Coffee inhibits the reactivation of glucocorticoids by 11beta-hydroxysteroid dehydrogenase type 1: a glucocorticoid connection in the anti-diabetic action of coffee? Atanasov AG, Dzyakanchuk AA, Schweizer RA, Nashev LG, Maurer EM, Odermatt A.
BMJ 2017; 359. Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes. Robin Poole, Oliver J Kennedy, Paul Roderick, Jonathan A Fallowfield, Peter C Hayes, Julie Parkes.
Lancet. 2016 Aug 27;388(10047):881-90. Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis. Cipriani A, Zhou X, Del Giovane C, Hetrick SE, Qin B, Whittington C, Coghill D, Zhang Y, Hazell P, Leucht S, Cuijpers P, Pu J, Cohen D, Ravindran AV, Liu Y, Michael KD, Yang L, Liu L, Xie P.
World J Biol Psychiatry. 2014 Jul;15(5):377-86. Coffee, caffeine, and risk of completed suicide: results from three prospective cohorts of American adults. Lucas M, O’Reilly EJ, Pan A, Mirzaei F, Willett WC, Okereke OI, Ascherio A.
Human Psychopharmacology Volume4, Issue1March 1989 Pages 33-39. Methylxanthines cause a decrease of prolactin plasma levels in healthy non‐pregnant women. M. Casas MdS. Ferre MDJ. Rodriguez MD, MCF. Jane MD.
J Neurosci. 2007 Jun 27;27(26):6956-64. Serotonin activates the hypothalamic-pituitary-adrenal axis via serotonin 2C receptor stimulation. Heisler LK, Pronchuk N, Nonogaki K, Zhou L, Raber J, Tung L, Yeo GS, O’Rahilly S, Colmers WF, Elmquist JK, Tecott LH.
Neurosci Lett. 2002 Oct 31;332(2):87-90. Modulation of the stress response by coffee: an in vivo microdialysis study of hippocampal serotonin and dopamine levels in rat. Yamato T, Yamasaki S, Misumi Y, Kino M, Obata T, Aomine M.
Clin Cancer Res. 2015 Apr 15;21(8):1877-87. Caffeine and Caffeic Acid Inhibit Growth and Modify Estrogen Receptor and Insulin-like Growth Factor I Receptor Levels in Human Breast Cancer. Rosendahl AH, Perks CM, Zeng L, Markkula A, Simonsson M, Rose C, Ingvar C, Holly JM, Jernström H.
Eur Arch Psychiatry Clin Neurosci. 2010 Dec;260(8):583-600. The hypothalamic-pituitary-adrenal axis and serotonin abnormalities: a selective overview for the implications of suicide prevention. Pompili M, Serafini G, Innamorati M, Möller-Leimkühler AM, Giupponi G, Girardi P, Tatarelli R, Lester D.
Cancer. 2009 Jun 15;115(12):2765-74. Relationship between caffeine intake and plasma sex hormone concentrations in premenopausal and postmenopausal women. Kotsopoulos J, Eliassen AH, Missmer SA, Hankinson SE, Tworoger SS.
Clin Exp Pharmacol Physiol. 2016 Dec;43(12):1208-1215. Beneficial effect of aspirin against interferon-α-2b-induced depressive behavior in Sprague Dawley rats. Bhatt S, Pundarikakshudu K, Patel P, Patel N, Panchal A, Shah G, Goswami S.
Acta Neurochir Suppl. 2015;120:141-5. Estrogen induces nitric oxide production via nitric oxide synthase activation in endothelial cells. Nevzati E, Shafighi M, Bakhtian KD, Treiber H, Fandino J, Fathi AR.
BMC Womens Health. 2005 Dec 20;5:12. An overlooked connection: serotonergic mediation of estrogen-related physiology and pathology. Rybaczyk LA, Bashaw MJ, Pathak DR, Moody SM, Gilders RM, Holzschu DL.
JAMA Psychiatry. 2015 Aug;72(8):794-802. Serotonin Synthesis and Reuptake in Social Anxiety Disorder. Frick A, Åhs F, Engman J, Jonasson M, Alaie I, Björkstrand J, Frans Ö, Faria V, Linnman C, Appel L, Wahlstedt K, Lubberink M, Fredrikson M, Furmark T.
Pharmacol Rep. 2010 Nov-Dec;62(6):1030-40. Effects of neurosteroids on the human corticotropin-releasing hormone gene. Budziszewska B, Zając A, Basta-Kaim A, Leśkiewicz M, Steczkowska M, Lasoń W, Kaciński M.
PLoS One. 2015 May 15;10(5):e0126469. Coffee Consumption, Newly Diagnosed Diabetes, and Other Alterations in Glucose Homeostasis: A Cross-Sectional Analysis of the Longitudinal Study of Adult Health (ELSA-Brasil). Yarmolinsky J, Mueller NT, Duncan BB, Bisi Molina Mdel C, Goulart AC, Schmidt MI.
Neonatology. 2014;106(3):235-40. Anti-Inflammatory Effect of Caffeine is Associated with Improved Lung Function after LPS-induced Amnionitis. Köroğlu OA, MacFarlane PM, Balan KV, Zenebe WJ, Jafri A, Martin RJ, Kc P.
Prog Neuropsychopharmacol Biol Psychiatry. 2006 Aug 30;30(6):1091-6. Increased plasma nitric oxide level associated with suicide attempt in depressive patients. Kim YK, Paik JW, Lee SW, Yoon D, Han C, Lee BH.
Am J Physiol Regul Integr Comp Physiol. 2003 Jun;284(6):R1631-5. An oxidized metabolite of linoleic acid stimulates corticosterone production by rat adrenal cells. Bruder ED, Ball DL, Goodfriend TL, Raff H.
Neuropsychopharmacology. 2014 Nov;39(12):2867-73. A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression. Brown ES, Park J, Marx CE, Hynan LS, Gardner C, Davila D, Nakamura A, Sunderajan P, Lo A, Holmes T.
J Clin Psychiatry 2015;76(12):1658–1667. Oxidative Stress and Antioxidant Parameters in Patients With Major Depressive Disorder Compared to Healthy Controls Before and After Antidepressant Treatment: Results From a Meta-Analysis. Sara Jiménez-Fernández, MD; Manuel Gurpegui, MD; Francisco Díaz-Atienza, MD; Lucía Pérez-Costillas, MD; Miriam Gerstenberg, MD; and Christoph U. Correll, MD
Biol Psychiatry. 2018 Jan 1;83(1):61-69. Elevated Translocator Protein in Anterior Cingulate in Major Depression and a Role for Inflammation in Suicidal Thinking: A Positron Emission Tomography Study. Holmes SE, Hinz R, Conen S, Gregory CJ, Matthews JC, Anton-Rodriguez JM, Gerhard A, Talbot PS.
Am J Clin Nutr. 1980 May;33(5):989-97. Caffeine and coffee: their influence on metabolic rate and substrate utilization in normal weight and obese individuals. Acheson KJ, Zahorska-Markiewicz B, Pittet P, Anantharaman K, Jéquier E.
Am J Physiol Gastrointest Liver Physiol. 2012 Feb 1;302(3):G397-405. The role of mechanical forces and adenosine in the regulation of intestinal enterochromaffin cell serotonin secretion. Chin A, Svejda B, Gustafsson BI, Granlund AB, Sandvik AK, Timberlake A, Sumpio B, Pfragner R, Modlin IM, Kidd M.
Neuropsychopharmacology. 2009 Jul;34(8):1885-903. Proof-of-Concept Trial with the Neurosteroid Pregnenolone Targeting Cognitive and Negative Symptoms in Schizophrenia. Marx CE, Keefe RS, Buchanan RW, Hamer RM, Kilts JD, Bradford DW, Strauss JL, Naylor JC, Payne VM, Lieberman JA, Savitz AJ, Leimone LA, Dunn L, Porcu P, Morrow AL, Shampine LJ.
Life Sci. 2014 Apr 17;101(1-2):1-9. Using caffeine and other adenosine receptor antagonists and agonists as therapeutic tools against neurodegenerative diseases: A review. Rivera-Oliver M, Díaz-Ríos M.
Neurosci Lett. 2016 Jan 12;611:106-11. Lipopolysaccharide induced anxiety- and depressive-like behaviour in mice are prevented by chronic pre-treatment of esculetin. Sulakhiya K, Keshavlal GP, Bezbaruah BB, Dwivedi S, Gurjar SS, Munde N, Jangra A, Lahkar M, Gogoi R.
Pharmacol Biochem Behav. 2000 May;66(1):39-45. Caffeine-induced increases in the brain and plasma concentrations of neuroactive steroids in the rat. Concas A, Porcu P, Sogliano C, Serra M, Purdy RH, Biggio G.
Circulation. 2015 Dec 15;132(24):2305-15. Association of Coffee Consumption With Total and Cause-Specific Mortality in 3 Large Prospective Cohorts. Ding M, Satija A, Bhupathiraju SN, Hu Y, Sun Q, Han J, Lopez-Garcia E, Willett W, van Dam RM, Hu FB.
Nutr Metab Insights. 2012 Sep 13;5:59-70. Effects of Caffeine on Metabolism and Mitochondria Biogenesis in Rhabdomyosarcoma Cells Compared with 2,4-Dinitrophenol. Vaughan RA, Garcia-Smith R, Bisoffi M, Trujillo KA, Conn CA.
Crisis. 2015;36(1):46-54. Exploratory investigation of biomarker candidates for suicide in schizophrenia and bipolar disorder. Youssef NA, Bradford DW, Kilts JD, Szabo ST, Naylor JC, Allen TB, Strauss JL, Hamer RM, Brancu M, Shampine LJ, Marx CE.
Atherosclerosis. 2001 Mar;155(1):37-44. Lipid peroxidation product 4-hydroxy-2-nonenal acts synergistically with serotonin in inducing vascular smooth muscle cell proliferation. Watanabe T, Pakala R, Katagiri T, Benedict CR.
Nature Medicine volume 23, pages 174–184 (2017). Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states. Furman D, Chang J, Lartigue L, Bolen CR, Haddad F, Gaudilliere B, Ganio EA, Fragiadakis GK, Spitzer MH, Douchet I, Daburon S, Moreau JF, Nolan GP, Blanco P, Déchanet-Merville J, Dekker CL, Jojic V, Kuo CJ, Davis MM, Faustin B.
Horm Metab Res. 2004 Oct;36(10):693-5. Lipid peroxidation at various estradiol concentrations in human circulation during ovarian stimulation with exogenous gonadotropins. Kaya H, Sezik M, Ozkaya O, Dittrich R, Siebzehnrubl E, Wildt L.
Neurosci Lett. 2001 Jul 27;308(1):25-8. Caffeine inhibits exercise-induced increase in tryptophan hydroxylase expression in dorsal and median raphe of Sprague-Dawley rats. Lim BV, Jang MH, Shin MC, Kim HB, Kim YJ, Kim YP, Chung JH, Kim H, Shin MS, Kim SS, Kim EH, Kim CJ.
Nat Neurosci. 2015 Aug;18(8):1094-100. The role of ventral striatal cAMP signaling in stress-induced behaviors. Plattner F, Hayashi K, Hernández A, Benavides DR, Tassin TC, Tan C, Day J, Fina MW, Yuen EY, Yan Z, Goldberg MS, Nairn AC, Greengard P, Nestler EJ, Taussig R, Nishi A, Houslay MD, Bibb JA.
Int J Immunopathol Pharmacol. 2017 Mar;30(1):13-24. Caffeine intake decreases oxidative stress and inflammatory biomarkers in experimental liver diseases induced by thioacetamide: Biochemical and histological study. Amer MG, Mazen NF, Mohamed AM.
Neuroscience. 2014 Dec 5;281:208-15. Caffeine potentiates the release of GABA mediated by NMDA receptor activation: Involvement of A1 adenosine receptors. Ferreira DD, Stutz B, de Mello FG, Reis RA, Kubrusly RC.
Can J Physiol Pharmacol. 2016 Sep;94(9):961-72. Modulatory effects of caffeine on oxidative stress and anxiety-like behavior in ovariectomized rats. Caravan I, Sevastre Berghian A, Moldovan R, Decea N, Orasan R, Filip GA.
Br J Nutr. 2012 Jan;107(1):86-95. Chronic caffeine intake decreases circulating catecholamines and prevents diet-induced insulin resistance and hypertension in rats. Conde SV, Nunes da Silva T, Gonzalez C, Mota Carmo M, Monteiro EC, Guarino MP.
Cell Mol Neurobiol. 1993 Jun;13(3):247-61. Chronic Caffeine Alters the Density of Adenosine, Adrenergic, Cholinergic, GABA, and Serotonin Receptors and Calcium Channels in Mouse Brain. Shi D, Nikodijević O, Jacobson KA, Daly JW.
Cancer. 2009 Jun 15;115(12):2765-74. Relationship Between Caffeine Intake and Plasma Sex Hormone Concentrations in Premenopausal and Postmenopausal Women. Kotsopoulos J, Eliassen AH, Missmer SA, Hankinson SE, Tworoger SS.
Nat Med. 2017 Feb;23(2):174-184. Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states. Furman D, Chang J, Lartigue L, Bolen CR, Haddad F, Gaudilliere B, Ganio EA, Fragiadakis GK, Spitzer MH, Douchet I, Daburon S, Moreau JF, Nolan GP, Blanco P, Déchanet-Merville J, Dekker CL, Jojic V, Kuo CJ, Davis MM, Faustin B.
Plant Foods Hum Nutr. 2012 Mar;67(1):82-7. Effects of the consumption of caffeinated and decaffeinated instant coffee beverages on oxidative stress induced by strenuous exercise in rats. Viana AL, Fonseca Md, Meireles EL, Duarte SM, Rodrigues MR, Paula FB.
Behav Brain Res. 2014 Sep 1;271:7-15. Evidence for anxiolytic effects of acute caffeine on anxiety-related behavior in male and female rats tested with and without bright light. Hughes RN, Hancock NJ, Henwood GA, Rapley SA.
Neuropharmacology. 2006 Jan;50(1):69-80. Caffeine promotes hyperthermia and serotonergic loss following co-administration of the substituted amphetamines, MDMA (“Ecstasy”) and MDA (“Love”). McNamara R, Kerans A, O’Neill B, Harkin A.
Life Sci. 1995;57(19):PL285-92. 24h withdrawal following repeated administration of caffeine attenuates brain serotonin but not tryptophan in rat brain: implications for caffeine-induced depression. Haleem DJ, Yasmeen A, Haleem MA, Zafar A.
Behav Pharmacol. 2012 Aug;23(4):339-47. Effect of long-term caffeine administration on depressive-like behavior in rats exposed to chronic unpredictable stress. Pechlivanova DM, Tchekalarova JD, Alova LH, Petkov VV, Nikolov RP, Yakimova KS.
Aliment Pharmacol Ther. 2003 Feb 15;17(4):595-601. Moderate coffee consumption increases plasma glutathione but not homocysteine in healthy subjects. Esposito F, Morisco F, Verde V, Ritieni A, Alezio A, Caporaso N, Fogliano V.
JAMA Psychiatry. 2016 Aug 1;73(8):789-95. Whole-Body Hyperthermia for the Treatment of Major Depressive Disorder. Janssen CW, Lowry CA, Mehl MR, Allen JJ, Kelly KL, Gartner DE, Medrano A, Begay TK, Rentscher K, White JJ, Fridman A, Roberts LJ, Robbins ML, Hanusch KU, Cole SP, Raison CL.
J Affect Disord. 2017 Sep;219:193-200. Severity of anxiety- but not depression- is associated with oxidative stress in Major Depressive Disorder. Steenkamp LR, Hough CM, Reus VI, Jain FA, Epel ES, James SJ, Morford AE, Mellon SH, Wolkowitz OM, Lindqvist D.
Biochemistry (Mosc). 2004 Jan;69(1):70-4. Effects of coffee consumption on oxidative susceptibility of low-density lipoproteins and serum lipid levels in humans. Yukawa GS, Mune M, Otani H, Tone Y, Liang XM, Iwahashi H, Sakamoto W
Neurotherapeutics. 2013 Jan;10(1):143-53. Neuroprotective and anti-inflammatory properties of a coffee component in the MPTP model of Parkinson’s disease. Lee KW, Im JY, Woo JM, Grosso H, Kim YS, Cristovao AC, Sonsalla PK, Schuster DS, Jalbut MM, Fernandez JR, Voronkov M, Junn E, Braithwaite SP, Stock JB, Mouradian MM.
Nutrients. 2017 Jan 10;9(1). pii: E56. Coffee Intake Is Associated with a Lower Liver Stiffness in Patients with Non-Alcoholic Fatty Liver Disease, Hepatitis C, and Hepatitis B. Hodge A, Lim S, Goh E, Wong O, Marsh P, Knight V, Sievert W, de Courten B.
Proc Natl Acad Sci U S A. 2015 Jun 23;112(25):7833-8. Caffeine acts through neuronal adenosine A2A receptors to prevent mood and memory dysfunction triggered by chronic stress. Kaster MP, Machado NJ, Silva HB, Nunes A, Ardais AP, Santana M, Baqi Y, Müller CE, Rodrigues AL, Porciúncula LO, Chen JF, Tomé ÂR, Agostinho P, Canas PM, Cunha RA.