Health effects of coffee

The health effects of coffee have been studied to determine how coffee drinking affects humans. Coffee contains several compounds which are known to affect human body chemistry. The coffee bean itself contains chemicals which are mild psychotropics for humans as a defense mechanism of the Coffea plant. These chemicals are toxic in large doses, or even in their normal amount when consumed by many creatures which may otherwise have threatened the beans in the wild. Coffee contains caffeine, which acts as a stimulant.

Recent research has uncovered additional stimulating effects of coffee which are not related to its caffeine content. Coffee contains a currently unknown chemical agent which stimulates the production of cortisone and adrenaline, two stimulating hormones.^[1]

For occasions when one wants to enjoy the flavor of coffee with almost no stimulation, decaffeinated coffee (also called decaf) is available. This is coffee from which most of the caffeine has been removed, by the Swiss water process (which involves the soaking of raw beans to remove the caffeine) or the use of a chemical solvent such as trichloroethylene ("tri"), or the more popular methylene chloride, in a similar process. Another solvent used is ethyl acetate; the resultant decaffeinated coffee is marketed as "natural decaf" because ethyl acetate is naturally present in fruit. Extraction with supercritical carbon dioxide has also been employed.

Decaffeinated coffee usually loses some flavor compared to normal coffee. There are also coffee alternatives that resemble coffee in taste but contain no caffeine (see below). These are available both in ground form for brewing and in instant form.

Caffeine dependency and withdrawal symptoms are well-documented.

Benefits

Reduced risk of Alzheimer's disease and Dementia

Several studies comparing moderate coffee drinkers (defined as 3–5 cups per day) with light coffee drinkers (defined as 0–2 cups per day) found that those who drank more coffee were significantly less likely to develop Alzheimer's disease later in life.^[2][3] A longitudinal study in 2009 found that moderate coffee drinkers had reduced risk of developing dementia in addition to Alzheimer's disease.^[4]

Reduced risk of gallstone disease

Drinking caffeinated coffee has been correlated with a lower incidence of gallstones and gallbladder disease in both men^[5] and women^[6] in two studies performed by the Harvard School of Public Health. A lessened risk was not seen in those who drank decaffeinated coffee. A recent study showed that roast coffee protected primary neuronal cells against hydrogen peroxide-induced cell death.^[7]

Reduced risk of Parkinson's disease

A study comparing heavy coffee drinkers (3.5 cups a day) with non-drinkers found that the coffee drinkers were significantly less likely to develop Parkinson's disease later in life.^[8] Likewise, a second study found an inverse relationship between the amount of coffee regularly drank and the likelihood of developing Parkinson's disease.^[9]

Cognitive performance

Many people drink coffee for its ability to increase short term recall.^[10]

Likewise, in tests of simple reaction time, choice reaction time, incidental verbal memory, and visuospatial reasoning, participants who regularly drank coffee were found to perform better on all tests, with a positive relationship between test scores and the amount of coffee regularly drunk. Elderly participants were found to have the largest effect associated with regular coffee drinking.^[11] Another study found that women over the age of 80 performed significantly better on cognitive tests if they had regularly drunk coffee over their lifetimes.^[12]

Analgesic enhancement

Coffee contains caffeine, which increases the effectiveness of pain killers, especially migraine and headache medications.^[13] For this reason, many over-the-counter headache drugs include caffeine in their formula.

Antidiabetic

Coffee intake may reduce one's risk of diabetes mellitus type 2 by up to half. While this was originally noticed in patients who consumed high amounts (7 cups a day), the relationship was later shown to be linear.^[14][15]

Liver protection

Coffee can also reduce the incidence of cirrhosis of the liver^[16] and has been linked to a reduced risk of hepatocellular carcinoma, a primary liver cancer that usually arises in patients with preexisting cirrhosis.^[17] The exact mechanism and the amount of coffee needed to achieve a beneficial effect have long been unclear.^[18] The cytokine transforming growth factor (TGF) beta has long been recognized for promoting fibrosis ability acting through the Smad family of transcription factors. In an interesting report recently published in the Journal of Hepatology, Gressner and colleagues provide the first mechanistic context for the epidemiological studies on coffee drinkers by showing that caffeine may have potent anti-fibrotic capabilities through its ability to antagonize the Smad pathway.^[19]

Cancer

Coffee consumption is also correlated to a reduced risk of oral, esophageal, and pharyngeal cancer.^[20][21] In ovarian cancer, no benefit was found.^[22] In the Nurses' Health Study, a modest reduction in breast cancer was observed in postmenopausal women only, which was not confirmed in decaffeinated coffee.^[23] According to one study, coffee protects the liver from cancer.^[24] Another preliminary study found a correlation between coffee consumption and a lower risk of aggressive prostate cancer.^[25]

Cardioprotective

Coffee moderately reduces the incidence of dying from cardiovascular disease, according to a large prospective cohort study published in 2008.^[26] A 2009 prospective study in Japan following nearly 77,000 individuals aged 40 to 79 found that coffee consumption, along with caffeine intake, was associated with a reduced risk of dying from cardiovascular disease.^[27]

Laxative/diuretic

Coffee is also a powerful stimulant for peristalsis and is sometimes considered to prevent constipation. However, coffee can also cause excessively loose bowel movements. The stimulative effect of coffee consumption on the colon is found in both caffeinated and decaffeinated coffee.^[28][29]

Practitioners in alternative medicine often recommend coffee enemas for "cleansing of the colon" due to its stimulus of peristalsis, although medicine has not proven any benefits of the practice.

Contrary to popular belief, caffeine does not act as a diuretic when consumed in moderation, and does not lead to dehydration or to a water-electrolyte imbalance; current evidence suggests that caffeinated beverages contribute to the body's daily fluid requirements no differently from pure water.^{[30][31][32][33]}

Antioxidant

Coffee contains the anticancer compound methylpyridinium. This compound is not present in significant amounts in other foods. Methylpyridinium is not present in raw coffee beans but is formed during the roasting process from trigonelline, which is common in raw coffee beans. It is present in both caffeinated and decaffeinated coffee, and even in instant coffee.^[34] Research funded by Kraft shows that roast coffee contains more lipophilic antioxidants and chlorogenic acid lactones and is more protective against hydrogen peroxide-induced cell death in primary neuronal cells than green coffee.^[7] The espresso method of extraction yields higher antioxidant activity than other brewing methods.^[35]

Prevention of dental caries

The tannins in coffee may reduce the cariogenic potential of foods. In vitro experiments have shown that these polyphenolic compounds may interfere with glucosyltransferase activity of mutans streptococci, which may reduce plaque formation.^[36]

Gout

Coffee consumption decreased risk of gout in men over age 40. In a large study of over 45,000 men over a 12-year period, the risk for developing gout in men over 40 was inversely proportional with the amount of coffee consumed.^[37]

Risks

Cancer

Over 1,000 chemicals have been reported in roasted coffee, and 19 are known rodent carcinogens;^[38] however, most substances cited as rodent carcinogens occur naturally and should not be assumed to be carcinogenic in humans at exposure levels typically experienced in day-to-day life.^[38]

Gastrointestinal problems

Coffee can damage the lining of the gastrointestinal organs, causing gastritis and ulcers. The consumption of coffee is therefore not recommended for people with gastritis, colitis, and ulcers.^[39]

Anxiety and sleep changes

Many coffee drinkers are familiar with "coffee jitters", a nervous condition that occurs when one has had too much caffeine. It can also cause anxiety and irritability, in some with excessive coffee consumption, and some as a withdrawal symptom. Coffee can also cause insomnia in some. In others it can cause narcolepsy.^[40]

Cholesterol

A 2007 study by the Baylor College of Medicine indicates that the diterpene molecules cafestol and kahweol, found only in coffee beans, may raise levels of low-density lipoprotein or LDL in humans.^[41] This increase in LDL levels is an indicator that coffee raises cholesterol. The Baylor study suggests a possible link between cafestol, kahweol and higher levels of cholesterol in the body.

Paper coffee filters have a property that binds to lipid-like compounds which allows the filter to remove most of the cafestol and kahweol found in coffee. Brew methods which do not use a paper filter, such as the use of a press pot, do not remove cafestol and kahweol from the final brewed product.^[42][43]

Blood pressure

Caffeine has previously been implicated in increasing the risk of high blood pressure; however, recent studies have not confirmed any association. In a 12-year study of 155,000 female nurses, large amounts of coffee did not induce a "risky rise in blood pressure"^[44] .^[45] Previous studies had already shown statistically insignificant associations between coffee drinking and clinical hypertension. Effect of coffee on morbidity and mortality due to its effect on blood pressure is too weak, and has not been studied. Other positive and negative effects of coffee on health would be difficult confounding factors.^[1]

Effects on pregnancy

Caffeine molecules are small enough to penetrate the placenta and slip into the baby's blood circulation. Unlike adults, organs and systems in fetuses are not full-fledged, therefore not capable of fully metabolizing caffeine and excreting it. The energy booster tends to linger in the fetus's blood ten times longer than in adults. High levels of caffeine are bound to accumulate in the baby's body with frequent maternal consumption of caffeine. Just like what it does to adults, caffeine could also send the baby's pulse and breathing rate racing and affect its sleep pattern for an extended duration.^[46]

A February 2003 Danish study of 18,478 women linked heavy coffee consumption during pregnancy to significantly increased risk of stillbirths (but no significantly increased risk of infant death in the first year). "The results seem to indicate a threshold effect around four to seven cups per day," the study reported. Those who drank eight or more cups a day (64 U.S. fl oz or 1.89 L) were at 220% increased risk compared with nondrinkers. This study has not yet been repeated, but has caused some doctors to caution against excessive coffee consumption during pregnancy.^[47]

Decaffeinated coffee is also regarded as a potential health risk to pregnant women when chemical solvents are used to extract the caffeine instead of other less invasive processes. The impact of these chemicals is debated, however, as the solvents in question evaporate at 80–90 °C, and coffee beans are decaffeinated before roasting, which occurs at approximately 200 °C. As such, these chemicals, namely trichloroethane and methylene chloride, are present in trace amounts at most, and may not pose a significant threat to embryos and fetuses.^{[citation needed]}

Iron deficiency anemia

Coffee consumption can lead to iron deficiency anemia in mothers and infants.^[48] Coffee also interferes with the absorption of supplemental iron.^[49]

Coronary artery disease

A 2004 study tried to discover why the beneficial and detrimental effects of coffee conflict. The study concluded that consumption of coffee is associated with significant elevations in biochemical markers of inflammation. This is a detrimental effect of coffee on the cardiovascular system, which may explain why coffee has so far only been shown to help the heart at levels of four cups (24 fl oz or 600 mL) or fewer per day.^[50]

The health risks of decaffeinated coffee have been studied, with varying results. One variable is the type of decaffeination process used; while some involve the use of organic solvents which may leave residual traces, others rely on steam.^{[citation needed]}

A study has shown that cafestol, a substance which is present in boiled coffee drinks, dramatically increases cholesterol levels, especially in women. Filtered coffee contains only trace amounts of cafestol.

Polymorphisms in the CYP1A2 gene may lead to a slower metabolism of caffeine. In patients with a slow version of the enzyme the risk for myocardial infarction (heart attack) is increased by a third (2–3 cups) to two thirds (>4 cups). The risk was more marked in people under the age of 59.^[51]

A Harvard study conducted over the course of 20 years of 128,000 people published in 2006 concluded that there was no evidence to support the claim that coffee consumption itself increases the risk of coronary heart disease. The study did, however, show a correlation between heavy consumption of coffee and higher degrees of exposure to other coronary heart disease risk factors such as smoking, greater alcohol consumption, and lack of physical exercise.^[52] The results apply only to coffee filtered through paper filters, which excludes boiled coffee and espresso, for example. Additionally, the lead researcher on this study acknowledged that subsets of the larger group may be at risk for heart attack when drinking multiple cups of coffee a day due to genetic differences in metabolizing caffeine.^{[citation needed]}

The Iowa Women's Health Study showed that women who consumed coffee actually had fewer cardiovascular disease incidents and lower cancer rates than the general population. For women who drank 6 or more cups, the benefit was even greater. However, this study excluded 35% of its original participants who already had cardiovascular disease and other chronic diseases when the study began. Since participants were all over the age of 55, no good conclusion can be drawn about the long term effect of coffee drinking on heart disease from this study.^[53]

See also

• Health effects of tea

References

1. ^ ^{a b} Klag MJ, Wang NY, Meoni LA, et al. (March 2002). "Coffee intake and risk of hypertension: the Johns Hopkins precursors study". Archives of internal medicine 162 (6): 657–62. doi:10.1001/archinte.162.6.657. PMID 11911719. 
2. ^ Maia, L.; de Mendonça, A. (July 2002). "Does caffeine intake protect from Alzheimer's disease?". European Journal of Neurology 9 (4): 377. doi:10.1046/j.1468-1331.2002.00421.x. 
3. ^ Lindsay, J.; et al. (2002). "Risk Factors for Alzheimer’s Disease: A Prospective Analysis from the Canadian Study of Health and Aging". Am J Epidemiol 156 (5): 445–453. doi:10.1093/aje/kwf074. 
4. ^ "Midlife Coffee And Tea Drinking May Protect Against Late-Life Dementia". ScienceDaily. January 15, 2009. http://www.sciencedaily.com/releases/2009/01/090114200005.htm. 
5. ^ Leitzmann, M. F.; et al. (1999). "A prospective study of coffee consumption and the risk of symptomatic gallstone disease in men". JAMA 281: 2106–12. doi:10.1001/jama.281.22.2106. 
6. ^ Leitzmann, M. F.; et al. (2002). "Coffee intake is associated with lower risk of symptomatic gallstone disease in women". Gastroenterology 123 (6): 1823–30. doi:10.1053/gast.2002.37054. 
7. ^ ^{a b} Chu, YF et al., Yi-Fang; Brown, Peter H.; Lyle, Barbara J.; Chen, Yumin; Black, Richard M.; Williams, Claire E.; Lin, Yi-Ching; Hsu, Chih-Wei et al. (2009). "Roasted coffees high in lipophilic antioxidants and chlorogenic acid lactones are more neuroprotective than green coffees". Journal of Agricultural and Food Chemistry 57 (20): 9801–9808. doi:10.1021/jf902095z. PMID 19772322. http://pubs.acs.org/doi/abs/10.1021/jf902095z. Retrieved 27 July 2010. 
8. ^ Webster Ross, G. et al., Association of Coffee and Caffeine Intake With the Risk of Parkinson Disease, JAMA, May 24, 2000, 283:20, ([1] accessed Nov 30, 2006)
9. ^ Benedetti M.D. et al., Smoking, alcohol, and coffee consumption preceding Parkinson’s disease, Neurology, 2000:55, 1350–1358. ([2] accessed Nov 30, 2006)
10. ^ Koppelstaeter F, Siedentopf C, Poeppel T, Haala I, Ischebeck A, Mottaghy F. Influence of caffeine =excess on activation patterns in verbal working memory. Radiological Society of North America, 2005, abstract no LPR06-05 link.
11. ^ Jarvis, M.J., Does caffeine intake enhance absolute levels of cognitive performance?, Psychopharmacology, 2 December 2005, 110:1–2, 45–52. ([3] accessed Nov 30, 2005).
12. ^ Johnson-Kozlow, M., et al., Coffee Consumption and Cognitive Function among Older Adults, Am J Epidemiol 2002; 156:842–850 ([4] accessed Nov 30, 2006)
13. ^ "Headache Triggers: Caffeine". WebMD. June 2004. http://www.webmd.com/content/article/46/1826_50681.htm. Retrieved 2006-08-14. 
14. ^ Salazar-Martinez E, Willett WC, Ascherio A, et al. (January 2004). "Coffee consumption and risk for type 2 diabetes mellitus". Ann. Intern. Med. 140 (1): 1–8. PMID 14706966. 
15. ^ Huxley R, Lee CM, Barzi F et al (2009). "Coffee, decaffeinated coffee, and tea consumption in relation to incident type 2 diabetes mellitus". Arch Intern Med 169 (22): 2053–2063. doi:10.1001/archinternmed.2009.439. PMID 20008687. 
16. ^ Klatsky AL, Morton C, Udaltsova N, Friedman GD (2006). "Coffee, cirrhosis, and transaminase enzymes". Arch. Intern. Med. 166 (11): 1190–5. doi:10.1001/archinte.166.11.1190. PMID 16772246. 
17. ^ Inoue M, Yoshimi I, Sobue T, Tsugane S (February 2005). "Influence of Coffee Drinking on Subsequent Risk of Hepatocellular Carcinoma: A Prospective Study in Japan". JNCI Journal of the National Cancer Institute 97 (4): 293–300. doi:10.1093/jnci/dji040. PMID 15713964. 
18. ^ Cadden IS, Partovi N, Yoshida EM (2007). "Review article: possible beneficial effects of coffee on liver disease and function". Aliment. Pharmacol. Ther. 26 (1): 1–8. doi:10.1111/j.1365-2036.2007.03319.x. PMID 17555416. 
19. ^ Gressner OA, Lahme B, Rehbein K, Siluschek M, Weiskirchen R, Gressner AM (2008). "Pharmacological application of caffeine inhibits TGF-beta-stimulated connective tissue growth factor expression in hepatocytes via PPARgamma and SMAD2/3-dependent pathways". J. Hepatol. 49 (5): 758–767. doi:10.1016/j.jhep.2008.03.029. PMID 18486259. 
20. ^ Rodriguez, T; Rodriguez T, Altieri A, Chatenoud L, Gallus S, Bosetti C, Negri E, Franceschi S, Levi F, Talamini R, La Vecchia C. (2 2004). "Risk factors for oral and pharyngeal cancer in young adults". Oral Oncol. 40 (2): 207–13. doi:10.1016/j.oraloncology.2003.08.014. PMID 14693246. 
21. ^ Tavani, A; Bertuzzi M, Talamini R, Gallus S, Parpinel M, Franceschi S, Levi F, La Vecchia C. (10 2003). "Coffee and tea intake and risk of oral, pharyngeal and esophageal cancer". Oral Oncol. 39 (7): 695–700. doi:10.1016/S1368-8375(03)00081-2. PMID 12907209. 
22. ^ Song YJ, Kristal AR, Wicklund KG, Cushing-Haugen KL, Rossing MA (2008). "Coffee, tea, colas, and risk of epithelial ovarian cancer". Cancer Epidemiol. Biomarkers Prev. 17 (3): 712–6. doi:10.1158/1055-9965.EPI-07-2511. PMID 18349292. 
23. ^ Ganmaa D, Willett WC, Li TY, et al. (2008). "Coffee, tea, caffeine and risk of breast cancer: a 22-year follow-up". Int. J. Cancer 122 (9): 2071–6. doi:10.1002/ijc.23336. PMID 18183588. 
24. ^ Coffee Health Benefits : Coffee may protect against disease
25. ^ "Can Coffee Lower The Risk of Prostate Cancer?". http://www.npr.org/templates/story/story.php?storyId=121343438. 
26. ^ Lopez-Garcia, E, van Dam RM, Li TY, Rodriguez-Artalejo F, Hu FB. "The Relationship of Coffee Consumption with Mortality." Annals of Internal Medicine (2008) Jun 17;148(12):904-14. [5]
27. ^ Koizumi A, Mineharu Y, Wada Y, Iso H et al. (2011). "Coffee, green tea, black tea and oolong tea consumption and risk of mortality from cardiovascular disease in Japanese men and women". Journal of Epidemiology and Community Health 65: 230–240. doi:10.1136/jech.2009.097311. 
28. ^ Brown SR, Cann PA, Read NW (April 1990). "Effect of coffee on distal colon function" (PDF). Gut 31 (4): 450–3. doi:10.1136/gut.31.4.450. PMC 1378422. PMID 2338272. http://gut.bmj.com/cgi/reprint/31/4/450. 
29. ^ Rao SS, Welcher K, Zimmerman B, Stumbo P (February 1998). "Is coffee a colonic stimulant?". Eur J Gastroenterol Hepatol 10 (2): 113–8. doi:10.1097/00042737-199802000-00003. PMID 9581985. 
30. ^ Really? The Claim: Caffeine Causes Dehydration The New York Times
31. ^ Armstrong LE, Casa DJ, Maresh CM, Ganio MS (2007). "Caffeine, fluid-electrolyte balance, temperature regulation, and exercise-heat tolerance". Exerc. Sport Sci. Rev. 35 (3): 135–140. doi:10.1097/jes.0b013e3180a02cc1. PMID 17620932. http://www.medscape.com/viewarticle/559762.  (Review article, free full text available at Medscape with registration)
32. ^ Armstrong LE, Pumerantz AC, Roti MW, Judelson DA, Watson G, Dias JC, Sokmen B, Casa DJ, Maresh CM, Lieberman H, Kellogg M. (2005). "Fluid, electrolyte, and renal indices of hydration during 11 days of controlled caffeine consumption". Int. J. Sport Nutr. Exerc. Metab. 15 (3): 252–265. PMID 16131696.  (Placebo controlled randomized clinical trial)
33. ^ Grandjean AC, Reimers KJ, Bannick KE, Haven MC (October 2000). "The effect of caffeinated, non-caffeinated, caloric and non-caloric beverages on hydration". J. Am. Coll. Nutr. 19 (5): 591–600. PMID 11022872. http://www.jacn.org/cgi/content/full/19/5/591. 
34. ^ "COFFEE CAN PREVENT COLON CANCER". The Naked Scientists. BBC. 2003-10-19. http://www.thenakedscientists.com/html/Shows/2003.10.19.htm#3. Retrieved 2006-11-17. 
35. ^ López-Galilea I, Andueza S, di Leonardo I, Paz de Peña M, Cid C. Influence of torrefacto roast on antioxidant and pro-oxidant activity of coffee. Food Chemistry, 94;(1):75-80.
36. ^ Touger-Decker, R. & van Loveren, C., Sugars and dental caries, American Journal of Clinical Nutrition, October 2003, 78:4, 881S-892S.
37. ^ Choi, HK; Willett W, Curhan G (2007). "Coffee consumption and risk of incident gout in men: A prospective study". Arthritis Rheum 56 (6): 2049–55. doi:10.1002/art.22712. PMID 17530645. http://www3.interscience.wiley.com/cgi-bin/abstract/114269884. 
38. ^ ^{a b} Ames BN, Gold LS (1998). "The causes and prevention of cancer: the role of environment". Biotherapy 11 (2–3): 205–20. doi:10.1023/A:1007971204469. PMID 9677052. 
39. ^ "Gastritis". AJC. http://www.ajc.com/health/altmed/shared/health/alt_medicine/ConsConditions/Gastritiscc.html. Retrieved 2008-10-09. ^{[dead link]}
40. ^ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2919675/ Study, Narcolepsy and caffeinated beverages, Authors Thangh et al.
41. ^ Ricketts ML, Boekschoten MV, Kreeft AJ, Hooiveld GJ, Moen CJ, Müller M, Frants RR, Kasanmoentalib S, Post SM, Princen HM, Porter JG, Katan MB, Hofker MH, Moore DD. (2007). "The cholesterol-raising factor from coffee beans, cafestol, as an agonist ligand for the farnesoid and pregnane X receptors". Molecular Endocrinology 21 (7): 1603–16. doi:10.1210/me.2007-0133. PMID 17456796. 
42. ^ van Dusseldorp, M.; Katan, MB; van Vliet, T; Demacker, PN; Stalenhoef, AF (1991). "Cholesterol-raising factor from boiled coffee does not pass a paper filter". Arteriosclerosis, Thrombosis, and Vascular Biology (Dallas: American Heart Association) 11 (3): 586–593. ISSN 1524-4636. PMID 2029499. http://atvb.ahajournals.org/cgi/reprint/11/3/586.pdf 
43. ^ Urgert, Rob; van der Weg, Guido; Kosmeijer-Schuil, Truus G.; van de Bovenkamp, Peter; Hovenier, Robert; Katan, Martijn B. (1995). "Levels of the Cholesterol-Elevating Diterpenes Cafestol and Kahweol in Various Coffee Brews". Journal of Agricultural and Food Chemistry (Washington: American Chemical Society) 43 (8): 2167–2172. doi:10.1021/jf00056a039. http://pubs.acs.org/doi/abs/10.1021/jf00056a039 
44. ^ William Cromie, "Coffee Gets Cleared of Blood Pressure Risk", Harvard Gazette. November 10, 2005 (accessed August 1, 2006 at http://www.news.harvard.edu/gazette/2005/11.10/06-coffee.html)
45. ^ Wolfgang C. Winkelmayer, MD, ScD, Meir J. Stampfer, MD, DrPH, Walter C. Willett, MD, DrPH, Gary C. Curhan, MD, ScD, "Habitual Caffeine Intake and the Risk of Hypertension in Women", JAMA. 2005;294(18):2330-2335. doi: 10.1001/jama.294.18.2330 ,(accessed June 6, 2011 at http://jama.ama-assn.org/content/294/18/2330.abstract?etoc)
46. ^ "Caffeine and Pregnancy". http://pregnancydietplan101.com/caffeine-and-pregnancy. 
47. ^ Wisborg K, Kesmodel U, Bech BH, Hedegaard M, Henriksen TB (February 2003). "Maternal consumption of coffee during pregnancy and stillbirth and infant death in first year of life: prospective study". BMJ 326 (7386): 420. doi:10.1136/bmj.326.7386.420. PMC 149440. PMID 12595379. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=149440. 
48. ^ Muñoz LM, Lönnerdal B, Keen CL, Dewey KG (September 1988). "Coffee consumption as a factor in iron deficiency anemia among pregnant women and their infants in Costa Rica". Am. J. Clin. Nutr. 48 (3): 645–51. PMID 3414579. http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=3414579. 
49. ^ Dewey KG, Romero-Abal ME, Quan de Serrano J, et al. (July 1997). "Effects of discontinuing coffee intake on iron status of iron-deficient Guatemalan toddlers: a randomized intervention study". Am. J. Clin. Nutr. 66 (1): 168–76. PMID 9209186. http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=9209186. 
50. ^ Zampelas A, Panagiotakos DB, Pitsavos C, Chrysohoou C, Stefanadis C (October 2004). "Associations between coffee consumption and inflammatory markers in healthy persons: the ATTICA study.". The American journal of clinical nutrition 80 (4): 862–7. PMID 15447891. 
51. ^ Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H (March 2006). "Coffee, CYP1A2 Genotype, and Risk of Myocardial Infarction". JAMA: the Journal of the American Medical Association 295 (10): 1135–41. doi:10.1001/jama.295.10.1135. PMID 16522833. 
52. ^ Lopez-Garcia E, van Dam RM, Willett WC, et al. (May 2006). "Coffee Consumption and Coronary Heart Disease in Men and Women: A Prospective Cohort Study". Circulation 113 (17): 2045–53. doi:10.1161/CIRCULATIONAHA.105.598664. PMID 16636169. 
53. ^ Andersen LF, Jacobs DR, Carlsen MH, Blomhoff R (May 2006). "Consumption of coffee is associated with reduced risk of death attributed to inflammatory and cardiovascular diseases in the Iowa Women's Health Study.". The American journal of clinical nutrition 83 (5): 1039–46. PMID 16685044. 

External links

• "British Coffee Association". http://www.britishcoffeeassociation.org. 
• "Coffee Health Risks: For the moderate drinker, coffee is safe says Harvard Women’s Health Watch". Harvard Health Publications. http://www.health.harvard.edu/press_releases/coffee_health_risk. Retrieved 24 November 2010. 
• Osterweil, Neil. "Coffee and Your Health". WebMD. http://www.webmd.com/food-recipes/features/coffee-new-health-food. Retrieved 24 November 2010.