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Get Permission Shanmugam: Coffee, will it be Healthy Choice


Introduction

Coffee is the world’s beloved drink. It contains a complex mixture of chemicals that provide important amounts of chlorogenic acid and caffeine. It is the most important agricultural commodity in international trade. Arabica coffee and Robusta coffee are the two major species used in the coffee production. In fact, Coffee offers few nutrients, but it contains more than thousands of chemicals which occur naturally such as carbohydrates, lipids, nitrogenous compounds, vitamins, minerals, alkaloids and phenolic compounds, a number of which are potentially healthful (and others potentially harmful). The character impact compounds of coffee are not present in the green state but are mainly formed during roasting. The findings on the potential harmful effects of coffee consumption have historically been reported, and the great saint Jagadguru Sri Kanji Maha Periavar from Tamil Nadu Urged not to have either coffee or tea.

Bioactive componenets present in coffee

The term ‘Bioactive Compounds’ commonly refers to minor food constituents that exert biological functions other than nutritional functions. These compounds are commonly found in plants, and in a few animals that feed on them, and their chemical structures and biological functions vary widely.

Figure 1

Bioactive compounds present in coffee

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Caffeine

(1,3,7-trimethylxanthine) is an alkaloid compound which is naturally occurring compound of coffee. A Cup of coffee gives an energizing jolt because it naturally contains caffeine. The Linus Pauling Caffeine Institute, USA, notes that caffeine is quickly absorbed by all our body’s tissues, including the brain, and stimulates the nervous system. The amount of caffeine depends on the type of coffee and method of preparations. A standard cup of brewed coffee gives us 100 milligrams of caffeine. The high amount of caffeine occurs in the blood flow within 15-45 min of consumption, peaking approximately 60 minutes post-consumption. It freely crosses the blood- brain barrier like lipid soluble compound, and it has influence in our neural function attributed to energy balance. Caffeine is rapidly absorbed through the gastrointestinal (GI) tract and moves through cellular membranes with the same efficiency as when it is absorbed and circulated to tissue. Caffeine is metabolized by the liver and results in metabolites like paraxanthine (1,7-dimethylxanthine), theophylline (1,3-dimethyl-xanthine), and theobromine (3,7-dimethyl-xanthine) by the action of an enzyme.

Trigonelline

Beans from C. arabica species contain higher amounts of this compound, compared with C. canephora, and as with chlorogenic acids, trigonelline undergoes changes and degradation during roasting; hence, dark roasted coffees contain low amounts. However, 10–20% of the original amount of trigonelline is converted into Nicotinic Acid (Niacin).1 In addition to its vitamin function, niacin is also involved in other bioactive functions, presenting antidiabetic, 2 antioxidant and hepatoprotective. 3 effects in vitro and in animal studies.

N-Methylpyridinium

The compound N-Methylpyridinium and other pyridinium derivatives are additional thermal degradation products generated by the decarboxylation of Trigonelline.

β-carbolines

These are alkaloids formed in coffee mainly during roasting and the two identified β-carbolines in coffee are norharman and harman. The total concentration of these compounds in the brew is highly variable in the literature, from 4 to 80 µg per 100 mL, but typical concentrations are reported to be in the range of 4–20 µg per 100 mL, being primarily dependent on the coffee species. Roasted C. canephora beans have consistently higher amounts of β-carbolines than C. arabica beans. 4, 5, 6

Melanoidins and polysaccharides

Coffee melanoidins have gained importance because of their contribution to, the antioxidant and antimicrobial effects of coffee. 7 This is, due to the incorporation of Chlorogenic acids and other bioactive compounds into their structure during roasting.4 As melanoidins are not digested, they may act, in combination with coffee polysaccharides (mainly galactomannans and type II arabinogalactans), as soluble dietary fibres. They are largely indigestible and thus fermented in the gut.8, 9 A recent study concluded that the consumption of 0.5–2 g melanoidins per day (present in 2–5 cups) contributes up to 20% of the recommended 10 g of daily soluble dietary fibre intake. It has also been hypothesized that these substances may stimulate the growth of beneficial bacteria in the lower digestive tract.10

Coffee consumption has been associated with higher concentrations of serum total cholesterol and low density lipoprotein cholesterol. Cafestol and kahwoel are two diterpenes found in coffee oil. Diterpenes are the main cholesterol-raising compounds in coffee, but they are mostly removed by paper filters. Therefore, unfiltered coffee is a significant source of diterpenes, whereas the consumption of filtered coffee results in very little increase in serum cholesterol.

Chlorogenic acid is one of the biologically active compounds that found in coffee, slow absorption of carbohydrate. It is one chemical compound in coffee which found in Easter family and formed in between trans- cinnamic and quinic acid which are useful nutritional phenol. It also is known as 5-O-caffeoylquinic acid which ranges in between 70-350 mg in a 200 ml (7-oz) cup of coffee in which it contains about 35-175 Mg of caffeic acid.6

Harmful components present in coffee

A number of Studies highlighted that coffee as a potential source of certain unwanted/toxic constituents, such as Ochratoxin A, 11 Furan, 12, 13 Heavy Metals. 14, 15 A few compounds derived from microbial contamination (Ocratoxin A, Biogenic Amines), Pesticides or Chemical reactions that occur during the roasting process (mainly acrylamide furan and polycyclic aromatic hydrocarbons– PAH) have been of concern to health authorities such as the Food and Drug Administration (FDA), Food and Agriculture Organization of the United Nations (FAO) and the European Food Safety Authority (EFSA)

.

Figure 2

Harmful substances present in coffee

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Ocratoxin A derived from green bean contamination with mould and can be avoided by carefully harvesting, processing and storing coffee, which is reflected in good quality. In the European Union, regulation 1881/2006 states that for roasted coffees, the maximum limit is 5 µg per kg.

Pesticides comprise a large number of substances belonging to different chemical groups, which are used to control plant diseases, pests or weeds. They can be neurotoxic or inhibit vital metabolic reactions in living beings, targeting different mechanisms, and individual pesticides present different levels of toxicity. In order to protect human safety and health resulting from pesticide application during coffee production, many countries have put these chemicals under strict legislation and surveillance. In the United States, the FDA establishes the maximum amount of a pesticide allowed to remain in food, as part of the process of regulating pesticides. Presently, tolerance limits for about 43 pesticides in coffee are listed by the FDA. In Japan, the maximum tolerated residual limits are amongst the lowest (often 0.01 ppm).

Acrylamide, furan and PAH are derived from reactions that occur during roasting, more specifically Maillard reaction and pyrolysis33, the US FDA (FDA, 2016) reported that coffee is a significant source of acrylamide exposure for adults, and European Commission’s recommended indicative value is 450 µg acrylamide per kg of roast and ground coffee, a level which is generally achievable for commercial products.

Furan, Hydroxy Methyl Furfural (HMF) and Furfural are heterocyclic, low molecular weight molecules with a furan ring and potential carcinogenicity in common. Furan has been classified as a possible carcinogen (Group 2B) by the International Agency for Research on Cancer (IARC). In coffee, these compounds are formed during the roasting stage mainly via thermal degradation/Maillard reaction of reducing sugars, alone or in combination with amino acids or via the thermal degradation of amino acids.

PAH, from which benzo[a]pyrene is the most relevant from a toxicity point of view, can be formed in coffee and other foods that are severely roasted or exposed to very high temperatures. This compound is classified by the IARC as probably carcinogenic to humans. However, the level of exposure to PAH from coffee is low and within the safe limits set by International Agencies.16

Biogenic amines are organic bases of low molecular weight that participate in the regular metabolic processes of plants, microorganisms and animals. They are produced in the body and can also be provided by the diet and from the microbial flora of the intestine; at high concentrations, however, they can pose a toxicological risk. Examples include histidine, tyramine, tryptamine, cadaverine and putrescine. Histidine is the most toxic and is associated with a hypotensive effect and headaches. Putrescine, cadaverine and tyramine seem to be toxic in higher doses in animals, but the individual sensitivity to these compounds in humans varies considerably and causes different responses. In coffee, biogenic amines originate from the action of microbial enzymes on amino acids during fermentative processes, suggesting inappropriate storage or low-quality defective fermented seeds. Roasting may deconjugate and increase the amount of some free biogenic amines, whilst most other amines are degraded.17, 1

Coffee too has its health benefits

Figure 3
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Coffee intake reduces the risk of liver damage in people at high risk for liver disease including hepatic injury, cirrhosis, and hepatocellularcarcinoma. Pyridinium derivatives have also been reported to present antioxidant/chemopreventive, 18 Hepatoprotective, 19 vasoprotective 20 and antithrombotic effects. 21 A total number of 72 (5.6%) studies have investigated to identify the effect of coffee consumption on liver disorders, namely, liver function/enzymes in general and gallstones/gallstone disease. Overall, this evidence, largely from observational studies, is showing coffee to have a protective effect on the liver.

Coffee consumption is also inversely associated with the risk of Parkinson’s disease in men and women who have never used postmenopausal estrogen. 22 The risk of Alzheimer’s disease is lower in those who regularly consume caffeine containing coffee than in those who do not drink it.23 Many studies show that coffee consumption may help prevent several chronic diseases. In particular, long-term coffee consumption is associated with significant dose dependent reductions in the risk of developing Type-2 Diabetes. 24

Trigonelline has gained importance due to its potential contribution to the protective effect of coffee against diseases. In vitro and animal studies have reported different involvements of trigonelline against type 2 diabetes, 2 as well as neuroprotective, 25, 26 antitumour 27 and phytoestrogenic effects. 1 It has been reported that like trigonelline, n-methylpyridinium promoted higher glucose utilization in liver cells, stimulating cellular energy metabolism and contributing to the protective effect against type 2 diabetes. 28

β-carbolines have been recently associated with poten- tially positive effects, including neurological ones, with antidepressive and neuroprotective properties. It has also been suggested that they may reduce the risk of diabetes.

Chlorogenic acid can able to exert important roles in glucose and lipid metabolism regulation and on the other related disorders, e.g., diabetes, cardiovascular disease (CVD), obesity, cancer, and hepatic steatosis. 11 As with chlorogenic acids, 29 it has been hypothesized that melanoidins can enhance immune-stimulating properties and contribute significantly to reducing the risk of colon cancer 30, 31, 32 which might occur in different ways: i) by increasing the elimination rate of carcinogens through higher colon motility and faecal output, ii) by decreasing colon inflammation through improved microbiota balance (prebiotic effect) and iii) by serving as a ‘sponge’ for free radicals in the gut.4

Figure 4

Risk Associated with Consumption of Coffee

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Allergy

Coffee consumption associated with risk of Allergies. Anaphylaxis symptoms arises due to caffeine present in coffee. 33

Bone Health

The most frequently reported condition associated with coffee consumption is poor bone health. These adverse effect is reported only in lean compared to overweight/ obese individuals, 34 and in females, not males.35 with high daily coffee consumption,36, 37 Caffeine leads to a slight decrease in the efficiency of calcium absorption in gastrointestinal tract. Thus, an adequate intake of calcium and vitamin D and elimination of coffee intake to 2–3cups/day may help reduce the risk of osteoporosis and its related fracture particularly in elderly adults.

Cardio Vascular Disease

Coffee may show unfavourable acute cardiovascular and metabolic effects with regard to endothelial function. Risks of raised blood pressure/hypertension in coffee consumers are also apparent within the literature, and this pressor effect may be caused by a coffee-induced increase in adrenaline concentrations. 38, 39, 40 Coffee consumers also appear to be at an increased risk of higher homocysteine concentrations, an independent risk factor for CVD. 41, 42 Caffeine is a major component of coffee, and appears to exert most of its biological effects through the antagonism of the adenosine receptor. Adenosine is an endogenous inhibitory neuromodulator that prompts feelings of drowsiness, and thus caffeine induces generally stimulatory effects in the Central Nervous System. In addition, the physiological effects of caffeine intake include acute elevation of blood pressure, increasing metabolic rate, and diuresis. It should be considered that coffee does have modest cardiovascular effects such as tachycardia, high blood pressure, and occasional arrhythmia. The acute effects of coffee on the cardio vascular system might arise in the time immediate to coffee intake or in more susceptible individuals. Coffee consumption has been associated with higher concentrations of serum total cholesterol and low density lipoprotein cholesterol. Cafestol and kahwoel are two diterpenes found in coffee oil. Diterpenes are the main cholesterol-raising compounds in coffee, but they are mostly removed by paperfilters. Therefore, unfiltered coffee is a significant source of diterpenes, whereas the consumption of filtered coffee results in very little increase in serum cholesterol. 43 A direct dose-dependent effect is also evident and another study has quantified a 1.66 and 1.58 mg/dL increase in Low Density Lipoprotein (LDL)-cholesterol per daily cup of coffee consumed by men and women, respectively. 44, 45 Moreover, abstinence from coffee for at least 6 weeks will lower cholesterol concentrations in the general population, 46 and in hypercholesterolemic patients. 47 This negative effect of coffee on cholesterol concentrations, is owing to higher concentrations of diterpenes (kahweol and cafestol) in such coffee preparations. 48

Fertility

Coffee drinking decrease fertility in female. Reduce a chance of woman’s to be pregnant by about 27%. Coffee intake cause male infertility azoospermia or oligospermia. Influence semen parameters, but also sperm DNA integrity. 49, 50

Harmonal Problem

Caffeine consumption Menstrual disturbances; premenstrual syndrome; menstrual function (menstrual pattern, dysmenorrhea); menopausal/climacteric symptoms (hot flashes and night sweats); onset of menopause; salivary cortisol; sex hormone and other hormone levels (estradiol, testosterone); erectile dysfunction; anterior pituitary hormones. 51

Women Health

Females who drink 31-250 mg of caffeine/day had a 3/2-fold rise in the chances of developing fibrocystic breast disease and females who drink over 500 mg/day had a double increase in the probability of developing Breast tissue cysts in women cysts. 51 Drinking coffee when pregnant, caffeine will also reach the foetus, and child is highly sensitive to caffeine. Therefore, heavy weight coffee drinker while pregnant, at least reduce coffee intake not more than one cup per day.

Additional risks of coffee consumption were apparent for pregnant women (for example, relative to pregnancy complications, birth outcomes, or the health of the infant). Although these risks were noted in 26 out of the 50 studies, many were linked with higher coffee consumption. 52 Indeed, some studies did report positive (beneficial) effects on certain pregnancy/infant health outcomes, such as the risk of pre-term delivery, 53 or childhood acute leukemia. 54 Drinking coffee when pregnant, caffeine will also reach the foetus, and child is highly sensitive to caffeine. Therefore, during pregnancy the coffee intake shall be reduced to not more than one cup per day.

Conclusion

Coffee consumption is used for social activity, leisure, improvement of work performance. The negative effects of coffee tend to emerge in excessive drinking, so it is the best to avoid heavy coffee intake. This review covers the health benefits and adverse effects associated with drinking coffee. Overall, results of this review show that the risks of coffee consumption outweigh consumer’s health benefits clearly for the majority of health outcomes considered. Hence, we should find alternative for coffee such as our traditional health drinks, ragi malt, gruel/porridge prepared from millets and nuts to lead a healthy life.

Source of Funding

None.

Conflict of Interest

None.

References

1 

A Farah A Riedel C M Hochkogler R Lang G Bytof I Lantz T Hofmann V Somoza N-methylpyridinium, a degradation product of trigonelline upon coffee roasting, stimulates respiratory activity and promotes glucose utilization in HepG2 cellsFood Function20125345462

2 

O. Yoshinari K. Igarashi Anti-Diabetic Effect of Trigonelline and Nicotinic Acid, on KK-Ay MiceCurr Med Chem201017202196202

3 

Jonathan Arauz Yadira Rivera-Espinoza Mineko Shibayama Liliana Favari Rosa Elena Flores-Beltrán Pablo Muriel Nicotinic acid prevents experimental liver fibrosis by attenuating the prooxidant processInt Immunopharmacology201528124451

4 

A Farah Y.-F Chu Coffee constituentsCoffee: Emerging Health Effects and Disease PreventionIFT Press/Willey-BlackwellUSA20122158

5 

D A C Rodrigues S Casal A Farah β-CarbolinesCoffee, Chemistry, Quality and Health ImplicationsRoyal Society of Chemistry London, UK. In Press2017

6 

Irene Rebelo Susana Casal Coffee: A Dietary Intervention on Type 2 Diabetes?Curr Med Chem201724437683

7 

José A. Rufián-Henares Francisco J. Morales Functional properties of melanoidins: In vitro antioxidant, antimicrobial and antihypertensive activitiesFood Res Int20074089951002

8 

Rosa Cinzia Borrelli Fabrizio Esposito Aurora Napolitano Alberto Ritieni Vincenzo Fogliano Characterization of a New Potential Functional Ingredient:  Coffee SilverskinJ Agricultural Food Chem2004525133843

9 

Diana Gniechwitz Birgit Brueckel Nicole Reichardt Michael Blaut Hans Steinhart Mirko Bunzel Coffee Dietary Fiber Contents and Structural Characteristics As Influenced by Coffee Type and Technological and Brewing ProceduresJ Agricultural Food Chem200755261102734

10 

Vincenzo Fogliano Francisco J. Morales Estimation of dietary intake of melanoidins from coffee and breadFood Funct20112211723

11 

I Studerrohr D R Dietrich J Schlatter C Schlatter Ochratoxin A and coffee. Mitteilungen aus demMitteilungen aus dem Gebiete der Lebensmitteluntersuchung und Hygiene19948571927

12 

Colin Crews Dominic Roberts Sigrid Lauryssen Gerard Kramer Survey of furan in foods and coffees from five European Union countriesFood Additives and Contaminants: Part B20092295981939-3210, 1939-322910.1080/02652030903095408Informa UK Limitedhttps://dx.doi.org/10.1080/02652030903095408

13 

M.S. Altaki F.J. Santos M.T. Galceran Occurrence of furan in coffee from Spanish market: Contribution of brewing and roastingFood Chem20111264152732

14 

Caroline M. Taylor Jean Golding Joseph Hibbeln Alan M. Emond Environmental Factors Predicting Blood Lead Levels in Pregnant Women in the UK: The ALSPAC StudyPLoS ONE201389e72371

15 

Arkadiusz Nędzarek Agnieszka Tórz Beata Karakiewicz Jeremy Simon Clark Maria Laszczyńska Agnieszka Kaleta Concentrations of heavy metals (Mn, Co, Ni, Cr, Ag, Pb) in coffee.Acta Biochimica Polonica2013606237

16 

Scientific opinion of the panel on contaminants in the food chain on a request from the European commission on polycyclic aromatic hydrocarbons in foodEFSA (European Food Safety Authority)20087241114

17 

Engeseth Glória Potential adverse effects of coffee bioactive amines to human healthCoffee: Chemistry, Quality, and Health Implications2017UK. In pressLondon

18 

Veronika Somoza Michael Lindenmeier Elisabeth Wenzel Oliver Frank Helmut F. Erbersdobler Thomas Hofmann Activity-Guided Identification of a Chemopreventive Compound in Coffee Beverage Using in Vitro and in Vivo TechniquesJ Agric Food Chem2003512368619

19 

J Gebicki A Marcinek S Chlopicki J Adamus The use of quaternary pyridinium compounds for vasoprotection and/or hepatoprotectionPatent2008

20 

Roman Lang Anika Wahl Timo Stark Thomas Hofmann Urinary N-methylpyridinium and trigonelline as candidate dietary biomarkers of coffee consumptionMol Nutr Food Res20115511161323

21 

Bartlomiej Kalaska Lukasz Piotrowski Agnieszka Leszczynska Bartosz Michalowski Karol Kramkowski Tomasz Kaminski Antithrombotic Effects of Pyridinium Compounds Formed from Trigonelline upon Coffee RoastingJ Agricultural Food Chem20146213285360

22 

Cunhara Demendonc¸aa Therapeutic opportunities for caffeine in Alzheimer’sdisease and other neurodegenerative disordersJ Alzheimers Dis201020S12

23 

P Nawrot S Jordans J Rotstein Hugenholtz A Feeley M J Eastwood Food Addit Contam200320130

24 

Annett Riedel Christina Maria Hochkogler Roman Lang Gerhard Bytof Ingo Lantz Thomas Hofmann N-Methylpyridinium, a degradation product of trigonelline upon coffee roasting, stimulates respiratory activity and promotes glucose utilization in HepG2 cellsFood Funct20145345462

25 

B N Hong T H Yi R Park S Y Kim T H Kang Coffee improves auditory neuropathy in diabetic miceNeuroscience Letters200844133026

26 

Chihiro Tohda Tomoharu Kuboyama Katsuko Komatsu Search for Natural Products Related to Regeneration of the Neuronal NetworkNeurosignals2005141-2344510.1159/000085384

27 

Nobuhiro Hirakawa Rieko Okauchi Yutaka Miura Kazumi Yagasaki Anti-Invasive Activity of Niacin and Trigonelline against Cancer CellsBiosci, Biotechnol, Biochem20056936538

28 

R. Korpelainen J. Korpelainen J. Heikkinen K. Väänänen S. Keinänen-Kiukaanniemi Lifestyle factors are associated with osteoporosis in lean women but not in normal and overweight women: a population-based cohort study of 1222 womenOsteoporos Int20031413443

29 

Paola Vitaglione Vincenzo Fogliano Nicoletta Pellegrini Coffee, colon function and colorectal cancerFood Function20123991622

30 

Ana S.P. Moreira Manuel A. Coimbra Fernando M. Nunes Cláudia P. Passos Sónia A.O. Santos Armando J.D. Silvestre Chlorogenic acid–arabinose hybrid domains in coffee melanoidins: Evidences from a model systemFood Chem201518513544

31 

Vincenzo Fogliano Francisco J. Morales Estimation of dietary intake of melanoidins from coffee and breadFood Function20112211723

32 

M Garsetti N Pellegrini C Baggio F Brighenti B Folmer A Farah Human wellbeing - Sociability, performance and health84Elsevier2000493510

33 

Kumiya Sugiyama Tatsurai Cho Masamitsu Tatewaki Shogo Onishi Tatsuya Yokoyama Naruo Yoshida Anaphylaxis due to caffeineAsia Pacific Allergy20155155

34 

HE Meyer JI Pedersen EB LOken A Tverdal Aziza Mounach Asmaa Rezqi Dietary Factors and the Incidence of Hip Fracture in Middle-aged Norwegians: A Prospective StudyAm J Epidemiol1997145211723

35 

AE Maghraoui M Ghazi S Gassim I Ghozlani A Mounach A Rezqi Risk factors of osteoporosis in healthy Moroccan menMusculoskeletal Disord2010111148

36 

P Smits G Pieters T Thien The role of epinephrine in the circulatory effects of coffeeClin Pharmacol Ther19864044317

37 

P. Smits T. Thien A. van't Laar Influence of slow calcium-channel blockade on the cardiovascular effects of coffeeEur J Clin Pharmacol19863021715

38 

Paolo Palatini Giulio Ceolotto Fabio Ragazzo Francesca Dorigatti Francesca Saladini Italia Papparella CYP1A2 genotype modifies the association between coffee intake and the risk of hypertensionJ Hypertens20092781594601

39 

E Strandhagen S Landaas D S Thelle Folic acid supplement decreases the homocysteine increasing effect of filtered coffee. A randomised placebo-controlled studyEur J Clin Nutr 2003571114117

40 

Elisabeth Strandhagen Henrik Zetterberg Nibia Aires Mona Palmér Lars Rymo Kaj Blennow The methylenetetrahydrofolate reductase C677T polymorphism is a major determinant of coffee-induced increase of plasma homocysteine: A randomized placebo controlled studyInt J Mol Med 2004138115

41 

S Slow W E Miller D O McGregor M B Lee M Lever P M George Trigonelline is not responsible for the acute increase in plasma homocysteine following ingestion of instant coffeeEur J Clin Nutr200458912536

42 

B. D'Avanzo L. Santoro A. Nobili C. Lavecchia Coffee Consumption and Serum CholesterolPrev Med199322221924

43 

B Berndt Gbm Mensink M Kohlmeier L Kohlmeier E Kottgen Lipoprotein metabolism and coffee intake—who is at risk?. Ernahrungswiss19933216375

44 

Benedicte Christensen Annhild Mosdol Lars Retterstol Sverre Landaas Dag S Thelle Abstention from filtered coffee reduces the concentrations of plasma homocysteine and serum cholesterol—a randomized controlled trialAm J Clin Nutr20017433027

45 

O H Forde S F Knutsen E Arnesen D S Thelle The Tromso heart study: coffee consumption and serum lipid concentrations in men with hypercholesterolaemia: an randomised intervention study.BMJ198529064728935

46 

Nasheen Naidoo Cynthia Chen Salome A Rebello Karl Speer E Shyong Tai Jeanette Lee Cholesterol-raising diterpenes in types of coffee commonly consumed in Singapore, Indonesia and India and associations with blood lipids: A survey and cross sectional studyNutr J2011101

47 

Martha M. Werler Mahsa M. Yazdy James R. Kasser Susan T. Mahan Robert E. Meyer Marlene Anderka Maternal Cigarette, Alcohol, and Coffee Consumption in Relation to Risk of ClubfootPaediatr Perinat Epidemiol 2015291310

48 

Thaís de Mérici Domingues e Paula Felipe Lioe Teh Shang Hélio Chiarini-Garcia Fernanda Radicchi Campos Lobato de Almeida Caffeine Intake during Pregnancy: What Are the Real Evidences?J Pharm Pharmacol20175524960

49 

Tian Yu Sarah C. Campbell Chris Stockmann Casey Tak Katherine Schoen Erin A. S. Clark Pregnancy-induced changes in the pharmacokinetics of caffeine and its metabolitesJ Clin Pharmacol20165655906

50 

Amy E. Chadwick Peggy M. Zoccola Wilson S. Figueroa Erin M. Rabideau Communication and Stress: Effects of Hope Evocation and Rumination Messages on Heart Rate, Anxiety, and Emotions After a StressorHealth Commun20163112144759

51 

Gretchen L. Gierach Neal D. Freedman Abegail Andaya Albert R. Hollenbeck Yikyung Park Arthur Schatzkin Coffee intake and breast cancer risk in the NIH-AARP diet and health study cohortInt J Cancer2012131245260

52 

J Alonso C Sosa M E Verde A Balsamo M Moraes M Zolessi L Bertolino J Amaral Di Giovanni J P Risk factors for term small for gestational age: a case-control study in an Uruguayan populationInt J Gynecol Obst2012119276276

53 

Jacqueline Clavel Stéphanie Bellec Sandra Rebouissou Florence Ménégaux Jean Feunteun Catherine Bonaïti-Pellié Childhood leukaemia, polymorphisms of metabolism enzyme genes, and interactions with maternal tobacco, coffee and alcohol consumption during pregnancyEur J Cancer Prev200514653140

54 

Scientific opinion on the safety of caffeineEFSA J201513



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