Medical Herbalism. A Journal for the Clinical Practitioner. A New Look at an Old Devil. The Health Ben e fits of Cof fee

Transcription

1 Medical Herbalism A Journal for the Clinical Practitioner (2009) Volume 16, Number 1: p 1-17 A New Look at an Old Devil by Paul Bergner It pos sesses antidi a betic, anti-in flam ma tory, antioxidant, cholagogue, hepatoprotective, neuroprotective, and an ti de pres sant ef fects. Reg u lar con sump tion re duces the in ci dence of car diac-re lated and all-cause mor tal ity in a dose-de pend ent man ner. It is the only herbal rem edy shown consistently to ex tend life in ep i de mi o log i cal stud ies. It has been pro posed as a func tional food by the pres ti gious Brit ish Jour nal of Nu tri tion (Dórea). This pan a cea would un doubt edly be named Herb of the Cen tury but for its name: Cof fee. Re search over the last ten years has seen the emer gence of sci en tific con sen sus on the broad health ben e fits of Caffea arabica, one of the world s most fre quently con - sumed herbal de coc tions. Cof fee, lumped with such agents as nic o tine and al co - hol, has been demonized not only in con tem po rary al ter - na tive and con ven tional med i cine; but also go ing back cen tu ries in the his tory of Ara bia and Is lam, and more re - cently in tem per ance move ments in Eu rope and North Amer ica. Moral judg ments about cof fee in vari ably arise from the stim u lat ing and habit-form ing char ac ter of caf - feine. In the Ot to man Em pire, re li gious de bates raged about whether it was an in tox i cant like al co hol or opium, or was oth er wise le gal in Is lamic law. The even tual edict was that al though it was an in tox i cant, it was sim i - lar to the wine of Par a dise de scribed in the Quran, that will nei ther pain their heads nor cloud their rea son and it is not con sid ered an in tox i cant by Is lamic schol ars to day. The cri te rion is that it does not im pair judg ment. Eu ro pean and North Amer i can Chris tian tem per ance move ments mil i tated against cof fee and tea as well as al - co hol; and the first ver sion of the FDA reg u la tion of opium and marijuana also proposed making coffee and caffeine into illegal or controlled substances. Neg a tive at ti tudes bor der ing on pu ri tan i cal fun da - men tal ism per sist to day in the field of al ter na tive med i - cine, where a high pri or ity is of ten placed on re moval of cof fee or caf feine from the diet with out con sid er ation of its ac tual harm ful or ben e fi cial ef fects on a pa tient s chief pre sent ing com plaint, con sti tu tion, or over all health; and usu ally with com plete ig no rance of its po ten - tial ben e fits. Be low, we de scribe the po ten tial ben e fits and harms of cof fee con sump tion so the prac ti tio ner may make an in formed judg ment as to the pri or ity that might be placed on re moval or re duc tion of cof fee con sump - tion in any par tic u lar case. The Health Ben e fits of Cof fee EF FECTS ON LON GEV ITY Cof fee has a well-doc u mented ben e fit on over all mor tal ity, and in light of this it must be con sid ered a tonic to the car dio vas cu lar sys tem and over all health. Early pop u la tion stud ies sug gested that cof fee drink ing might in crease over all mor tal ity, but re cent large and better-con trolled in ves ti ga tions show just the op po site. A pro spec tive study of more than 120,000 sub jects by the Har vard School of Pub lic Health found that in di vid - u als at the high est level of cof fee con sump tion (6 or more cups per day) had about a 20% re duced over all mor tal ity rate (in ei ther men or women) com pared to those who drank cof fee less than once per month. Some ben e fit was also seen in women who con sumed 2 4 cups per day, and in men who drank 4 6 cups. The de - crease in over all mor tal ity was mainly due to a de crease in car diac deaths (Lopez-Gar cia et al., 2008). Re cent stud ies in Fin land and Ja pan also found re duced over all mor tal ity for cof fee drink ers com pared to non-drink ers (Happonen et al.; Iso et al.). The Finn ish trial showed that each ad di tional cup of cof fee per day re duced the over all mor tal ity rate by about 4% re sults very sim i lar to those from the Har vard study. CAR DIO VAS CU LAR DIS EASE In the Har vard trial cited above (Lopez-Gar cia et al.), over all car diac mor tal ity was lower in heavy cof fee drink ers than in non-drink ers. Sig nif i cantly, the trial was con trolled for smok ing, an ad just ment omit ted in many ear lier stud ies that sug gested a link be tween cof - fee drink ing and heart at tacks. This was con firmed in an other re cent pro spec tive trial of 127,000 pa tients en - rolled in a Kai ser Permanente plan in Cal i for nia. Af ter seven years, di ag nosed cor o nary ar tery dis ease (CAD)

2 was found to be re lated to cof fee only among cur rent or for mer smok ers. For those who had never smoked, cof - fee had no sig nif i cant cor re la tion to CAD. The re search - ers con cluded that the dis ease in smok ers was un re lated to cof fee drink ing (Klatsky et al.). Cof fee con sump tion like wise did not el e vate cor o nary risk in a re cent meta-anal y sis of 23 stud ies (Sofi et al.). The re sults were sim i lar to those from a 1994 meta-anal y sis (Kwachi et al.). Cof fee may slightly el e vate blood pres sure, but only to a clin i cally in sig nif i cant de gree. Pooled data from 18 stud ies of cof fee s ef fect on blood pres sure found that, taken for more than seven days, cof fee raises sys tolic pres sure by 1.22 mm Hg, and di a stolic pres sure by 0.49 mm Hg. The av er age in take was 24 ounces, given to pre - vi ous non-drink ers (Noordzij et al.). An other trial ex am - ined blood pres sure el e va tion with larger amounts of cof fee and for a lon ger du ra - tion. In the 11 stud ies re viewed, me dian du ra tion was 56 days and me dian dose was 40 ounces of cof fee per day. Sys tolic and di a stolic blood pres sure in creased by 2.4 (range, 1.0 to 3.7) mm Hg and 1.2 (range, 0.4 to 2.1) mm Hg, re spec tively, with cof fee treat ment com pared to con - trol (Jee et al., 1999). The ef fect of cof fee in pa tients with es tab lished hy per ten sion (whether ha bit u ated or not) has not been mea sured, and may pos si bly be con tra- in di - cated. Cof fee can raise to tal cho les terol, LDL cho les terol, and tri glyc er ides in some in di vid u als but not with the form of cof fee most com monly con sumed. A re view of 14 tri als found av er age in creases in to tal cho les terol of 12 mg/dl; in LDL cho les terol of 6.5 mg/dl; and in tri - glyc er ides of 6 mg/dl. Most of the ef fect was ob served in those who con sumed 6 or more cups per day, and was ev i dent only in tri als of boiled (not fil tered) cof fee. The fil ter ing pro cess ap pears to re move the con stit u - ents re spon si ble for the el e va tion of lipids (Jee et al., 2001). Sys temic in flam ma tion is cur rently rec og nized as a sig nif i cant risk fac tor for car dio vas cu lar dis ease. Some ear lier stud ies sug gested that ha bit ual cof fee drink ing was cor re lated with higher mea sures of sys temic in flam - ma tion, such as C-re ac tive pro tein (Zampelas et al.). Three more re cent and better-con trolled tri als in di ver - gent pop u la tions doc u ment cor re la tions rang ing from no as so ci a tion be tween cof fee con sump tion and CRP in nor - mal con trols, to a pro tec tive ef fect of about 10% lower CRP for each ex tra cup of cof fee drunk by women with type II di a be tes (Lopez-Garcia 2006; Williams et al.; Kotani et al.). Cof fee has a well-documented benefit on over all mor tal ity, and... must be con sidered a tonic to the cardiovascular sys tem and over all health. DI A BE TES AND GLU COSE TOL ER ANCE Pop u la tion stud ies on three con ti nents have now doc - u mented a pro tec tive ef fect of cof fee against the risk of type II di a be tes. The pro tec tion is lin ear the more cof - fee an in di vid ual drinks, the lower their risk of di a be tes. In di vid u als drink ing 6 cups of cof fee per day have about half the risk of those who drink none at all. Stud ies have found pro tec tive ef fects rang ing from 30 60%, in creas - ing as con sump tion in creases (van Dam; Murakami et al.; Legrand and Scheen). The pro tec tive ef fect is not due ex - clu sively to caf feine, and is prob a bly due to chlorogenic acid and/or var i ous other an ti ox i dants in cof fee. Ei ther caffeinated or de caf fein ated cof fee im proves glu cose tol - er ance (van Dam). CAN CER Cof fee s con nec tion to var i ous can cers has been stud ied ex ten - sively, due to safety con cerns about this widely con sumed bev er age. A re view of ten stud ies found that cof - fee con sump tion is pro tec tive against liver can cer. On av er age, hepatocellular car ci noma was re - duced by 30% in mod er ate cof fee drink ers and 55% in heavy us ers (Bravi et al.). An other meta-anal y sis of nine stud ies ex - am ined the re la tion ship be tween cof fee drink ing and ei - ther pri mary liver can cer or hepatocellular car ci noma, and found sim i lar re sults. All stud ies ex am ined found a pro tec tive ef fect. An in crease of two cups of cof fee per day was as so ci ated with a 43% re duced in ci dence of the two types of liver can cer. This in cluded a 31% de crease in in di vid u als with out prior his tory of liver dis ease, and a 44% de crease in those with such a his tory (Larsson and Wolk). One large pop u la tion study (The Nurses Health Study) found a small pro tec tive ef fect of cof fee for breast can cer in postmenopausal women, but not in the group over all (Ganmaa et al.). A case-con trol study found a pro tec tive ef fect in premenopausal but not postmenopausal women with breast can cer who con - sumed 4 or more cups of cof fee per day. The risk was re - duced by about 40% (Baker et al.). A large study in Swe den, on the other hand, found no as so ci a tion be tween cof fee con sump tion and breast can cers in any group (Michels et al., 2002). Some early stud ies in di cated that cof fee may be pro - tec tive against co lon can cer. How ever, sev eral meta-anal y ses have failed to find any ef fect, ei ther pro - tec tive or caus ative (Tavani and La Vecchia; Michels et al., 2005; Naganuma et al.). Vol. 16 No. 1 Medical Herbalism Page 2

3 The only can cer with a pos si ble pos i tive cor re la tion to cof fee is blad der can cer. A re view of 37 tri als found a small in crease about 20% in blad der can cer among the heavi est cof fee drink ers. The au thors note that the re - sults could be due to higher rates of smok ing in cof fee drink ers (Zeegers et al.). Most of the tri als were not con - trolled for nic o tine use, and nic o tine is a well-es tab lished risk fac tor for blad der can cer. A re view of 10 case-con - trol stud ies in Eu rope among non-smok ers found no re la - tion ship be tween cof fee and blad der can cer ex cept in a small group that con sumed more than 10 cups of cof fee per day (Sala et al.). Other re views have found no cor re la tion be tween cof - fee con sump tion and a va ri ety of can cers. A re view of 23 stud ies found no re la tion ship, ei ther pro tec tive or ad - verse, be tween cof fee con sump tion and gas tric can cer (Botelho et al.). A re view of 14 tri als found no as so ci a - tion be tween cof fee and thy roid can cer (Mack et al.). Like wise, on meta-anal y sis, no cor re la tion was found be - tween cof fee con sump tion and pan cre atic (Ilart et al.) or pros tate (Dagnelie et al.) can cers. GAS TRO IN TES TI NAL AND GALL BLAD DER Cof fee has the same gen eral risks and ben e fits as other herbs con tain ing bit ter prin ci ples. A re view of cof fee s gas tro in tes ti nal ef fects showed that in some in di vid u als it pro duced gas tro in tes ti nal re flux. It was not found to be as so ci ated with dys pep sia. Cof fee pro motes peristalsis in the co lon at about the same rate as a 1,000 Kcal meal (Boekema et al.). The re cent pub lished re views of cof - fee s ef fect on gall stones all show a dose-de pend ent pro - tec tive ef fect (Boekema et al.; Lammert and Matern; Misciagna et al.; Shaffer). In one rep re sen ta tive study, in - di vid u als who con sumed 2 3 cups of cof fee per day had a 40% re duced risk of gall blad der dis ease. The risk for those who drank four cups or more was even less (Leitzmann et al.). NEU RO LOG I CAL CON DI TIONS A Har vard re view of 13 stud ies found a pro tec tive ef - fect of cof fee for Par kin son s dis ease. The risk was re - duced by about 30% for each 3 cups of cof fee con sumed (Hernán et al.). The pooled data from four stud ies con - ducted be tween 1990 and 2002 found a pro tec tive ef fect against Alz hei mer s dis ease in cof fee drink ers of about 30%. Such pro tec tion may be due to the anti-in flam ma - tory or the in su lin-sen si tiz ing ef fects of cof fee. Ex ten sive cur rent lit er a ture links in su lin re sis tance with hyperinsulinemia as a ma jor con trib ut ing fac tor to Alz - hei mer s dis ease (Barranco et al.). KID NEY STONES Be cause caf feine may in crease diuresis and the uri - nary ex cre tion of cal cium, it has been pro posed as a risk fac tor for cal cium kid ney stones. How ever, a trial con - ducted by re search ers at Har vard Uni ver sity found about a 40% re duced risk of kid ney stones in a group of pa tients who con sumed the most liq uids, com pared to the least; there was an ad di tional 9 10% re duc tion in risk for each ad di tional eight-ounce cup of caffeinated or de caf fein ated cof fee con sumed on a reg u lar ba sis (Curhan et al.). DE PRES SION AND SUI CIDE No sig nif i cant re search ap pears on the re la tion ship be tween cof fee, caf feine, and de pres sion. How ever, cof fee drink ing ap pears to be strongly in versely re - lated to the risk of sui cide, a nat u ral end point of de - pres sion. A 10-year study in a group of more than 86,000 women found that those who drank two or more cups of cof fee per day had about 40% the sui cide risk of non-drink ers (Kawachi et al., 1996). The pro tec tive ef fect was also pres ent in a group of more than 43,000 sub jects fol lowed for 15 years. How ever, in the group con sum ing greater than eight cups per day, there was an in crease in sui cide risk. It was im pos si ble to tell from the data whether the high amounts in duced de - pres sion or whether de pressed pa tients self-med i cated with cof fee (Tanskanen et al.). The Ad verse Ef fects of Cof fee INSOMNIA In oc ca sional us ers, or those who ex ceed their ha bit - ual in take, caf feine may cause in som nia (es pe cially if it is not cleared from the sys tem by bed time). See The Phar ma col ogy of Cof fee Con stit u ents for a dis cus sion of fac tors that af fect clear ance. Com plete tol er ance to the sleep-dis rupt ing ef fects of caf feine de vel ops af ter con - sum ing very large doses: 400 mg of caf feine, 3 times per day, for 7 days. Com plete tol er ance to sub jec tive ef fects of caf feine was ob served to de velop af ter con sump tion of 300 mg, 3 times per day, for 18 days; and pos si bly even sooner. Nor mal doses of caf feine such as are con sumed by ha bit ual us ers do not cause com plete tol er ance, and some level of sleep dis rup tion may still oc cur (Griffiths and Mumford). ANX I ETY The acute or chronic ef fects of caf feine may meet the cri te ria of acute or chronic anx i ety dis or der. Turn-of-the-cen tury herbal and med i cal texts de scribed a syn drome known as caffeinism, which in cluded most of the symp toms of anx i ety. The ta ble be low com pares the symp toms of caffeinism with the con ven tional di ag no sis of chronic anx i ety one form of stress in lay terms. In one study, pa tients with anx i ety dis or der rated their symp toms on a stan dard test. Their lev els of anx i ety and de pres sion cor re lated di rectly with the amount of caf - feine they con sumed. An other group of six anx i ety pa - Vol. 16 No. 1 Medical Herbalism Page 3

4 Energetics and constitutional affects of coffee Unani Tibb: Ac cord ing to Avicenna, cof fee is hot and dry in the first de gree, but he states that other ex perts con sider it cold in the first de gree. In Unani (four-hu - mors) med i cine, first de gree herbs are those that will nudge the pa tient to ward a tem per ate (neu tral) state, but not over shoot the mark to over heat or overly cool the pa tient. It for ti fies the mem bers, cleans the skin, and dries up humidities that are un der it, and gives an ex cel - lent smell to all the body (Wein berg and Bealer). This nearly-neu tral prop erty of cof fee al lows it to be drunk in larger quan ti ties than would be pos si ble with cold bit ter herbs such as Taraxacum, Mahonia, or Gen - tian. It may, how ever, ag gra vate the dry pa tient, es pe - cially those that are dry and cold. Chi nese Med i cine: Dr. Subhuti Dharmanada of the In - sti tute for Tra di tional Med i cine has pub lished an ex ten - sive ar ti cle on line char ac ter iz ing cof fee ac cord ing to Chi nese med i cine (Dharmananda.) He com pares its ac - tients who con sumed the caf feine equiv a lent of 1.5 to 3.5 cups of cof fee about the av er age for Amer i cans cut their in take to zero. Within months, five of the six were symp tom-free. Anx i ety symp toms do not oc cur in the ma jor ity of in di vid u als con sum ing 1 4 cups of cof fee per day; but in those ex hib it ing them, caf feine should be con sid ered as a pos si ble cause. HEART BURN AND IN DI GES TION Cof fee and caf feine may cause or worsen heart burn in some in di vid u als. This may be due to the ef fects of bit ter sub stances on the se cre tory ap pa ra tus of the stom ach. Caf feine it self also in creased acid se cre tions. See The Phar ma col ogy of Cof fee Con stit u ents for more de tails. PREMENSTRUAL SYN DROME A num ber of tri als dem on strate a con nec tion be tween caf feine con sump tion and the pres ence and se ver ity of premenstrual syn drome in a dose-de pend ent man ner (Rossignol; Rasheed et al.; Ader et al.; Rossignol et al., 1991). In one trial, risks for PMS in creased 700% in women con sum ing 8 10 cups of cof fee per day com pared to those who con sumed none (Rossignol and Bonnlander). The as so ci a tion has also been found in Asian women con sum ing caffeinated tea (Rossignol et al., 1989). Caf feine com petes with estradiol for clear ance via liver p-450 en zymes. Al co hol and var i ous pre scrip - tion drugs may also com pete for clear ance see the ac - com pa ny ing Phar ma col ogy of Cof fee Con stit u ents. The path way is de pend ent on the nu tri tional sta tus of a num - ber of micro nut ri ents, es pe cially mag ne sium, vi ta min tion to that of Bupleurum and states that it is a valu able ther apy for stag nated liver qi, with con stricted cir cu la - tion of blood, and con strained gall blad der func tion, with con stricted elim i na tion of damp and heat. Summarizing his descriptions: Fla vor: bit ter, partly sweet. Actions: dredges the liver to reg u late the flow of liver qi, purges the gall blad der, opens the heart or i fices, warms the blood cir cu la tion, de tox i fies, and gently tonifies. Cautions: While cof fee dredges the liver qi, it does not nec es sar ily smooth or soothe the liver qi. There fore, one has to be cau tious about the amount con sumed and cer tain in di vid u als will find the oth er wise de sir able ef - fects dis tress ing: re leas ing stag nated qi but not reg u lat - ing its flow. Ex ces sive amounts of cof fee will ag i tate the liver yang and even stim u late in ter nal wind. Pro longed use of ex ces sive amounts could thereby dam age the blood B-6, and zinc. All three nu tri ents are com monly de fi cient in the mod ern pop u la tion, and their sta tus may af fect the in ter ac tion of caf feine and es tro gen. AD DIC TION AND WITH DRAWAL Like many ad dic tive sub stances, caf feine con sump - tion in duces an ad ap ta tion which causes with drawal symp toms when caf feine is re moved (See Phar ma col - ogy). Af ter ha bit u a tion, the symp toms of chronic use are much less dra matic than ini tial symp toms in a non-ha bit - Cof fee for mu la tion Spices may be added to hot cof fee, or other herbs may be decocted or in fused in al ready-brewed cof fee Caffea and cloves. To en hance an ti ox i dant ef fects; more stim u lat ing and anticatarrhal. Caffea and Cassia cinnamomum. to en hance antidiabetic ef fects. Also en hances antioxidation. Caffea and Arctium lappa. En hances the ben e fi cial ef fects of both herbs on skin and liver Caffea and Urtica spp. Strong di uretic com bi na tion. Dry ing. Adds nu tri tional con tent to cof fee. Caffea and Paeonia lactiflora. En hances calm ing ef fects of cof fee. Sim i lar to Bupleurum and Paeonia com bi na tions in Chi nese med i cine. Vol. 16 No. 1 Medical Herbalism Page 4

5 u ated in di vid ual; the caf feine user may con - sume it to pre vent with drawal symp toms. With drawal symp toms may in clude: Head ache (50% of sub jects) Fa tigue De creased en ergy / ac tive ness De creased alert ness Drowsiness De creased con tent ed ness De pressed mood Dif fi culty con cen trat ing Ir ri ta bil ity Foggy / not clear headed Flu-like symp toms, nau sea, and mus cle pain or stiff - ness may also oc cur (Juliano and Griffiths). Se ver ity may be mild to ex treme (in ca pac i tat ing) clin i cally sig nif i - cant dis tress or func tional im pair ment may be pres ent in 10 15% of us ers on with drawal. Typ i cally, on set of symp toms oc curs h af ter ab sti nence, with peak in - ten sity at h, and for a du ra tion of 2 9 days. In gen - eral, the in ci dence or se ver ity of symp toms in creased with higher daily doses. Ab sti nence from doses as low as 100 mg/day pro duced symp toms, which may oc cur af ter as lit tle as 6 15 days of use. Caf feine does not meet the sci en tific cri te ria for ad dic - tion in most in di vid u als, be cause the un pleas ant ef fect of very large doses ef fec tively pro duces a ceil ing on dose-con sump tion. Caf feine use also does not have rein - forc ing prop er ties con sump tion does not au to mat i cally lead to a con tin u ous in crease in dos age. Sur vey data sug - gest that only 9% to 30% of caf feine con sum ers may be caf feine-de pend ent (ac cord ing to DSM-IV di ag nos tic cri te ria for a sub stance de pend ence syn drome), in clud ing feel ing com pelled to con tinue use de spite de sires and rec - om men da tions to the con trary (Dews et al.; Griffiths and Chausmer; Griffiths and Mumford; Griffiths and Woodson). RISKS IN PREG NANCY The ef fect of caf feine on preg nancy out comes, in clud - ing mis car riage and birth de fects, is con tro ver sial. Of con cern is the fact that caf feine clear ance is re duced dur - ing preg nancy; it may con cen trate in the fe tus at higher lev els than in the ma ter nal blood, and is cleared even more slowly there. Whereas the mother may drink two cups of cof fee the sec ond one be ing taken af ter the caf - feine from the first one has cleared from her sys tem caf - feine from both cups may re main on the fe tal side of the Symp toms of caffeinism (*) Symp toms of chronic anx i ety (**) Anx i ety Apprehension Tremors Trem bling Insomnia Isomnia Ner vous ir ri ta bil ity Nervousness Hys te ria Irrational thinking Heart palpitations Heart palpitations Mental confusion Difficult concentration Muscular weakness Motor weakness Physical exhaustion Chronic fa tigue Headaches Headaches (Felter and Lloyd) (Berkow) pla centa. For the mother who con sumes larger amounts of caf feine, the prob lem may be se vere. Many, but not all, ep i de mi o log i cal stud ies sug gest a con nec tion be tween caf feine and mis car riage. How ever, a re view of fif teen stud ies, tak ing into con sid er ation con found ing fac tors and re port ing bias, sug gests that the con nec tion has not been con clu sively dem on strated (Signorello and McLaughlin). One strong con found ing fac tor was dem on strated in a trial that as sessed caf feine in take be fore or early in preg nancy. The re search ers found no con nec tion be tween re ported caf feine con - sump tion and sub se quent mis car riages. They did find, how ever, that in ter views con ducted af ter a mis car riage tended to over-re port caf feine con sump tion (Savitz). An other re cent pro spec tive trial did find a con nec tion be tween caf feine con sump tion and mis car riage (Weng et al.). A meta-anal y sis of ten stud ies on caf feine con sump - tion dur ing preg nancy and its pos si ble re la tion ship to low birth weight was in con clu sive. Three stud ies showed lower birth weight only with high lev els of caf - feine con sump tion, and con cluded there was no ev i - dence of a re la tion ship be tween mod er ate amounts of caf feine and birth weight (Pacheco et al.). A re cent pro - spec tive study found re stric tion of fe tal growth strongly as so ci ated with caf feine con sump tion. The in creased risk was about 50% for in takes of more than 200 mg caf - feine per day (Boylan et al.). A re view of the po ten tial for caf feine to cause birth de - fects con cluded that ef fects seen with huge amounts of caf feine in an i mal tri als do not rep re sent a cred i ble risk for hu man moth ers (Chris tian and Brent). In view of the in con sis tent ev i dence, it would seem pru dent to avoid caf feine dur ing preg nancy, al though mod er ate amounts may not pro vide ac tual risk. Ac cord - ing to one safety re view, Cur rently avail able ev i dence sug gests that it may be pru dent for preg nant women to Vol. 16 No. 1 Medical Herbalism Page 5

6 limit cof fee con sump tion to 3 cups/d pro vid ing no more than 300 mg/d of caf feine to ex clude any in creased prob - a bil ity of spon ta ne ous abor tion or im paired fe tal growth. (Higdon and Frei). BONE HEALTH Coffee or caf feine con sump tion have been pro posed as risk fac tors for os teo po ro sis, but the ev i dence is con - tra dic tory and re ported as so ci a tions may be due to con - found ing fac tors in clud ing in suf fi cient in take of di etary cal cium in some caf feine con sum ers. As long ago as 1997, a re view of pub lished lit er a ture failed to find a con nec tion be tween cof fee in take and mark ers of bone den sity (Auquier et al.). Re cent lit er a ture re views and one pro spec tive trial sim i larly find no con nec tion be tween caf feine and bone den sity or os teo po ro sis (Jarupanich; Waugh et al.; Wetmore et al.). One re cent co hort study re ported an as so ci a tion be tween osteoporotic frac ture and caf feine in take only in women who con sumed four or more cups per day and who were si mul ta neously de fi cient in di etary cal cium in take (Hallström et al.). There was no as so ci a tion of os teo po ro sis with any level of caf feine con sump tion in women who con sumed the RDA of cal cium. AD RE NAL EF FECTS Nor mal sin gle doses of caf feine do not af fect adren a - lin or cortisol lev els. See the ac com pa ny ing ar ti cle on The Phar ma col ogy of Cof fee. At higher ex per i men tal doses of con cen trated caf feine, both cir cu lat ing adren a lin and cortisol may be slightly el e vated. In crease in lev els of adre nal hor mones raises the ques tion whether ha bit ual con sump tion of caf feine may re sult in ad re nal ex haus tion or in suf fi ciency. A search of the PubMed da ta base of the Na tional Li brary of Med i cine pro duces more than 11,000 ar ti cles on the topic of ad re nal in suf fi ciency or Ad di son s dis ease, but none of these de scribe any re la tion ship to caf feine or cof fee. The adren a lin-pro mot ing ef fect of higher caf feine doses ap pears to be due to re duc tion of adren a line clear ance rather than to stim u la tion of in - creased se cre tion. Caf feine may thus re duce stress on the ad re nals by re duc ing pro duc tion re quire ments. The mech a nism of in creased cortisol at high ex per i men tal doses ap pears to be through in creased ACTH from the pi - tu itary. The ex haus tion seen in cof fee with drawal may be due to the ex ag ger ated ef fects of adenosine rather than to any ad re nal ef fects. See The Phar ma col ogy of Cof fee Con stit - u ents. An em pir i cal ar gu ment for this is that the mal aise of cof fee with drawal usu ally dis ap pears af ter days, which would not oc cur in ad re nal ex haus tion. Cof - fee con sump tion may also in di rectly af fect ad re nal func - tion through the ef fects of sleep debt. Cof fee is of ten used by the in di vid ual in a state of sleep debt to stay alert. Sleep debt is ac com pa nied by el e vated cortisol lev els, dis rupted cortisol daily cy cle, and in su lin re sis tance. The en do crine dis rup tion of sleep debt will usu ally dis ap pear after about three days of 9.5 or more hours of sleep (Bergner). ACUTE CAF FEINE IN TOX I CA TION Acute caf feine over dose may oc cur with doses in ex - cess of about 300 mil li grams, de pend ing on body weight and level of caf feine tol er ance. Symp toms may in clude rest less ness, ner vous ness, ex cite ment, in som nia, flush - ing of the face, in creased uri na tion, gas tro in tes ti nal dis - tur bance, mus cle twitch ing, a ram bling flow of thought and speech, ir ri ta bil ity, ir reg u lar or rapid heart beat, and psychomotor ag i ta tion (En cy clo pe dia of Men tal Dis or - ders). In cases of much larger over doses, ma nia, de pres - sion, lapses in judg ment, dis ori en ta tion, disinhibition, de lu sions, hal lu ci na tions, and psy cho sis may oc cur (Medline Plus). In cases of ex treme over dose, death can re sult. The LD50 of caf feine in hu mans is de pend ent on weight and in di vid ual sen si tiv ity and is es ti mated to be about 150 to 200 mg per ki lo gram of body mass (roughly equiv a lent to cups of cof fee for an av er age adult) taken within a lim ited time frame that is de pend ent on half-life. Though achiev ing a le thal dose of caf feine would be ex cep tion ally dif fi cult with reg u lar cof fee, deaths have been re ported from over dos ing on caf feine pills; and serious symptoms of overdose requiring hospitalization have occurred from as little as 2 grams of caffeine. The Pharmacology of Coffee Constituents Cof fee con stit u ents to be con sid ered in clude: Caf feine Caf feine me tab o lites Polyphenols Bit ter prin ci ples Caf feine is highly wa ter-sol u ble, is rap idly ab sorbed in the stom ach and in tes tine, and rap idly cir cu lated to all the tis sues. It freely crosses the blood-brain bar rier and its dis - tri bu tion is close to equal in all tis sues and flu ids. When taken as cof fee, caf feine lev els peak about one hour af ter in ges tion. About 98% of caf feine is biotransformed in the liver to sec ond ary me tab o lites with the re main der ex creted in the urine or other flu ids un changed. The half-life is 3 4 hours in healthy adults, but may vary widely. It in creases to 5 10 hours in women tak ing oral con tra cep tives, and to Vol. 16 No. 1 Medical Herbalism Page 6

7 9 11 hours in preg nant women. It is biotransformed by the CYP1A2 sub set of the cytochrome p-450 sys tem. In the pre dom i nant re ac tion, one or more of its methyl groups may be re moved to yield pri mar ily paraxanthine, a smaller amount of theophylline, and a phys i o log i cally neg li gi ble amount of theobromine. Sec ond ary me tab o - lites are even tu ally con verted to uric acid de riv a tives and ex creted in the urine. This same CYP1A2 path way me - tab o lizes estradiol; ex cess caf feine may com pete with estradiol and thus con trib ute to hyperestrogenism, a com mon pat tern of fe male re pro duc tive pa thol ogy re - sult ing in premenstrual syn drome, fibrocystic breasts, and other pa thol o gies. Some phar ma ceu ti cal drugs are me tab o lized by the same path way, and caf feine may in - ter act with such med i ca tions (See ta ble). In ter ac tions may be ag gra vated or ame lio rated de pend ing on the nu - tri tional sta tus of mag ne sium, vi ta min B-6, and zinc, which are essential for normal functioning of the pathway. Some sub stances en hance the ac tiv ity of the CYP1A2 path way in the liver, and these may in crease both tol er - ance and the speed of caf feine clear ance. No ta ble on the list are nic o tine and in su lin. Smok ers can drink more cof - fee with less net caf feine ef fect. Like wise in di vid u als with hyperinsulinemia sec ond ary to in su lin re sis tance, with or with out type II di a be tes, may drink more cof fee with less net caf feine ef fect be cause of en hanced biotransformation and clearance. PHARMACODYNAMICS OF CAF FEINE Caf feine binds to re cep tors for adenosine (a reg u la - tory nu cle o tide with wide phys i o log i cal ac tiv ity) and blocks its ef fects. In the brain, adenosine is an in hib i tory neu ro trans mit ter; block ing it re sults in stim u la tion, with in creased ac tiv ity of do pa mine and glu ta mate. Cells rap - idly adapt to caf feine by in creas ing the num ber of adenosine re cep tors within 7 10 days. The re sult is a de - vel op ment of tol er ance as the re cep tors up-reg u late, with in creas ing doses nec es sary to achieve the same ef fects. There is a limit to this in crease in re cep tors, and caf feine con sum ers ha bit u ated to high doses do not ex pe ri ence the same ef fects as non-us ers. With drawal symp toms are pri mar ily due to ex cess adenosine ef fects in the caf - feine-adapted user, with fa tigue, de pres sion, leth argy, and head ache oc cur ring until adenosine effects normalize in 5 10 days. Caf feine in creases lev els of camp in cells via in hi bi - tion of the en zyme that nor mally breaks it down. In - creased camp in turn re duces the clear ance of epi neph rine (adren a lin) and drugs that re sem ble it, in - clud ing am phet amine and ephed rine; caf feine is thus used as a booster for ephed rine ef fects in herbal pep pills. The same mech a nism causes an in crease in hy dro - chlo ric acid secretion in the stomach. Caf feine me tab o lites Medications that may have interactions with caf - feine via com pe ti tion for the CYP1A2 sub set of the cytochrome p-450 sys tem: amitriptyline clomipramine clozapine cyclobenzaprine estradiol fluvoxamine haloperidol imipramine mexiletine naproxen olanzapine Drug-Herb In ter ac tions ondansetron phenacetin acetaminophen propranolol riluzole ropivacaine tacrine theophylline tizanidine verapamil Fac tors Af fect ing Caf feine Me tab o lism Slows metabolism Speeds metabolism Alcohol Nic o tine Asian ancestry Cau ca sian an ces try Male Fe male Fetus/newborn Child Oral con tra cep tives Liver dam age Preg nancy In su lin Vol. 16 No. 1 Medical Herbalism Page 7

8 At a dose of 250 mg, caf feine ap pears to have no ef fect on cortisol, epi neph rine, thy roid-stim u lat ing hor mone, growth hor mone, prolactin, or triiodothyronine in in di - vid u als ha bit u ated to its use (Spindel et al.). At a mg sin gle dose, a slight el e va tion of ACTH, cortisol, or epi neph rine may oc cur. A sig nif i cant body of re search into the ef fects of caf feine on the hy po tha lamic-pi tu - itary-ad re nal axis (HPA) shows that: Ef fects are gen er ally non-ex is tent at lower doses (Spindel; Spindel et al.; Tarnopolsky et al.). The thresh old for en do crine ef fects is be tween 250 and 500 mg caf feine per dose (the equiv a lent of rap idly con sum ing 3 5 cups of cof fee at a sit ting) (Spindel; Spindel et al.; Lane). Ef fects are mild or non-ex is tent in rest ing in di vid u als not un der stress (Spindel et al.; Van Soeren et al.). Both epi neph rine (adren a lin) and cortisol re sponses to ex er cise or stress may be in creased at the thresh old dose and above (Lane; Lane et al.; Lovallo et al.; al Absi et al.; Van Soeren et al.). Ef fects may be less in ha bit u ated caf feine us ers (Tarnopolsky et al.; Van Soeren et al.). Most caf feine is con verted to paraxanthine, and its phar ma co log i cal ef fects are added to those of caf feine. Paraxanthine in creases lipolysis, lead ing to el e vated glyc erol and free fatty acid lev els in the blood plasma a ben e fi cial ef fect for ex er cise per for mance. A smaller amount is con verted to theobromine (the prin ci pal al ka - loid in Ca cao) which di lates the blood ves sels and in - creases urine vol ume; this com pound is at least partly re spon si ble for the di uretic ef fect of caf feine in those not habituated to it. POLYPHENOLS The polyphenol con tent of cof fee, most no ta bly chlorogenic acid and its de riv a tives, has been the fo cus of ex ten sive re search in re cent years. Chlorogenic acid is a po tent an ti ox i dant with an in su lin-sen si tiz ing ef fect on cells. See the ac com pa ny ing dis cus sion of cof fee con - sump tion and di a be tes. See also the ta ble be low for a rank ing of cof fee with other foods that are high in an ti ox - i dant con tent. As a ref er ence, a cup of cof fee con tains more an ti ox i dants than a cup of blue ber ries, and has about 3.5 times the an ti ox i dant con tent per serv ing as green or black tea. Be cause most cof fee drink ers con - sume more than the one serv ing of cof fee, and be cause most do not con sume the other foods with any fre quency, cof fee is the high est source of to tal di etary an ti ox i dants in the av er age North Amer i can diet to day. This may be a crit i cal con sid er ation before recommending that individuals remove coffee from their diets. BIT TER PRINCIPLES The bit ter con stit u ents of cof fee give the bev er age ef - fects sim i lar to those of other bit ter herbs: stim u la tion of di ges tive se cre tions and of bile re lease and flow from the liver. See the ef fects of cof fee on di ges tion and gall blad - der func tion in the ac com pa ny ing ar ti cle. FOODS WITH THE HIGH EST AN TI OX I DANT CON TENT PER SERV ING Food Serv ing Mmol/serving of antioxidants Blackberries 1 cup Wal nuts 1 oz Straw ber ries 1 cup Ar ti chokes, pre pared 3 oz Cran ber ries 1 cup Cof fee 1cup Raspberries 1 cup Pecans 1 oz Blueberries 1 cup Cloves, ground 1 tsp Grape juice 8 oz Choc o late, bak ing, unsw. 1 oz Cran berry juice 8 oz Cher ries, sour 1 cup Wine, red 3.5 oz (Halvorsen et al.) Vol. 16 No. 1 Medical Herbalism Page 8

9 COFFEE REFERENCES Ader DN, South-Paul J, Adera T, Deuster PA. Cy cli cal mastalgia: prev a lence and as so ci ated health and be hav ioral fac tors. J Psychosom Obstet Gynaecol Jun;22(2):71-6. al Absi M, Lovallo WR, McKey B, Sung BH, Whitsett TL, Wil son MF. Hypothalamic-pituitary-adrenocortical responses to psycho - log i cal stress and caf feine in men at high and low risk for hy per - ten sion. Psychosom Med Jul-Aug;60(4): Auquier P, Manuel C, Molines C. Risk fac tors for postmenopausal os teo po ro sis. Re view of the lit er a ture Rev Epidemiol Sante Publique Sep;45(4): Baker JA, Beehler GP, Sawant AC, Jayaprakash V, McCann SE, Moysich KB. Con sump tion of cof fee, but not black tea, is as so ci - ated with de creased risk of premenopausal breast can cer. J Nutr Jan;136(1): Barranco Quintana JL, Allam MF, Serrano Del Castillo A, Fernández-Crehuet Navajas R. Alz hei mer s dis ease and cof fee: a quan ti ta tive re view. Neurol Res Jan;29(1):91-5. Bergner P. 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10 Jee SH, He J, Ap pel LJ, Whelton PK, Suh I, Klag MJ. Cof fee con - sump tion and se rum lipids: a meta-anal y sis of ran dom ized con - trolled clin i cal tri als. Am J Epidemiol Feb 15;153(4): Jee SH, He J, Whelton PK, Suh I, Klag MJ. The ef fect of chronic cof fee drink ing on blood pres sure: a meta-anal y sis of con trolled clin i cal tri als. Hy per ten sion Feb;33(2): Juliano LM, Griffiths RR. A crit i cal re view of caf feine with drawal: empirical validation of symptoms and signs, incidence, severity, and as so ci ated fea tures. Psychopharmacology (Berl) Oct;176(1):1-29. Epub 2004 Sep 21. Kawachi I, Colditz GA, Stone CB. Does cof fee drink ing in crease the risk of cor o nary heart dis ease? Re sults from a meta-anal y sis. Br Heart J Sep;72(3): Kawachi I, Willett WC, Colditz GA, Stampfer MJ, Speizer FE. A pro spec tive study of cof fee drink ing and sui cide in women. Arch In tern Med Mar 11;156(5): Klatsky AL, Koplik S, Kipp H, Fried man GD. The con founded re la - tion of cof fee drink ing to cor o nary ar tery dis ease. Am J Cardiol Mar 15;101(6): Epub 2008 Jan 18. Kotani K, Tsuzaki K, Sano Y, Maekawa M, Fujiwara S, et al. The re la tion ship be tween usual cof fee con sump tion and se rum C-re ac - tive pro tein level in a Jap a nese fe male pop u la tion. Clin Chem Lab Med Oct;46(10): Lammert F, Matern S. Ev i dence-based pre ven tion of cholecystolithiasis. Dtsch Med Wochenschr Jul 9;129(28-29): Lane JD. Neuroendocrine re sponses to caf feine in the work en vi - ron ment. Psychosom Med May-Jun;56(3): Lane JD, Pieper CF, Phillips-Bute BG, Bryant JE, Kuhn CM. Caf - feine af fects car dio vas cu lar and neuroendocrine ac ti va tion at work and home. Psychosom Med Jul-Aug;64(4): Larsson SC, Wolk A. Cof fee con sump tion and risk of liver can cer: a meta-anal y sis. Gastroenterology May;132(5): Epub 2007 Mar 24. Legrand D, Scheen AJ. Does cof fee pro tect against type 2 di a be - tes? Rev Med Liege Sep;62(9): Leitzmann MF, Willett WC, Rimm EB, Stampfer MJ, Spiegelman D, Colditz GA, Giovannucci E. A pro spec tive study of cof fee con - sump tion and the risk of symp tom atic gall stone dis ease in men. JAMA Jun 9;281(22): Lopez-Gar cia E, van Dam RM, Li TY, Ro dri guez-artalejo F, Hu FB. The relationship of coffee consumption with mortality. Ann Intern Med Jun 17;148(12): Lopez-Gar cia E, van Dam RM, Qi L, Hu FB. Cof fee con sump tion and mark ers of in flam ma tion and en do the lial dys func tion in healthy and di a betic women. Am J Clin Nutr Oct;84(4): Mack WJ, Pres ton-mar tin S, Dal Maso L, Galanti R, Xiang M, et al. A pooled anal y sis of case-con trol stud ies of thy roid can cer: cig a - rette smok ing and con sump tion of al co hol, cof fee, and tea. Can - cer Causes Con trol Oct;14(8): MedlinePlus. Caf feine over dose Re trieved on Michels KB, Willett WC, Fuchs CS, Giovannucci E. 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11 Spindel E. Ac tion of the methylxanthines on the pi tu itary and pi tu - itary-de pend ent hor mones. Prog Clin Biol Res. 1984;158: Spindel ER, Wurtman RJ, Mc Call A, Carr DB, Conlay L, Grif fith L, Ar nold MA. Neuroendocrine ef fects of caf feine in nor mal sub jects. Clin Pharmacol Ther Sep;36(3): Tarnopolsky MA, Atkinson SA, MacDougall JD, Sale DG, Sutton JR. Phys i o log i cal re sponses to caf feine dur ing en dur ance run ning in ha bit ual caf feine us ers. Med Sci Sports Exerc Aug;21(4): Tavani A, La Vecchia C. Cof fee, de caf fein ated cof fee, tea and can cer of the co lon and rec tum: a re view of ep i de mi o log i cal stud - ies, Can cer Causes Con trol Oct;15(8): Tanskanen A, Tuomilehto J, Viinamäki H, Vartiainen E, Lehtonen J, Puska P. Heavy cof fee drink ing and the risk of sui cide. Eur J Epidemiol. 2000;16(9): van Dam RM. Cof fee and type 2 di a be tes: from beans to beta-cells. Nutr Metab Cardiovasc Dis Jan;16(1): Epub 2005 Dec 13. Van Soeren MH, Sathasivam P, Spriet LL, Gra ham TE. Caf feine me tab o lism and epi neph rine re sponses dur ing ex er cise in us ers and non us ers. J Appl Physiol Aug;75(2): Waugh EJ, Lam MA, Hawker GA, McGowan J, Papaioannou A, et al. Risk fac tors for low bone mass in healthy year old women: A sys tem atic re view of the lit er a ture. Osteoporos Int Jun 4. Wein berg BA, Bealer BK. The World of Caf feine: the Sci ence and Cul ture of the World s Most Pop u lar Drug. New York: Routledge, Weng X, Odouli R, Li DK. Ma ter nal caf feine con sump tion dur ing preg nancy and the risk of mis car riage: a pro spec tive co hort study. Am J Obstet Gynecol Mar;198(3):279.e1-8. Epub 2008 Jan 25. Wetmore CM, Ichikawa L, LaCroix AZ, Ott SM, Scholes D. As so ci - a tion be tween caf feine in take and bone mass among young women: po ten tial ef fect mod i fi ca tion by de pot medroxyprogesterone ac e tate use. Osteoporos Int Apr;19(4): Epub 2007 Oct 9. Wil liams CJ, Fargnoli JL, Hwang JJ, van Dam RM, Blackburn GL, et al. Cof fee con sump tion is as so ci ated with higher plasma adiponectin con cen tra tions in women with or with out type 2 di a be - tes: a pro spec tive co hort study. Di a be tes Care Mar;31(3): Epub 2007 Dec 10. Zampelas A, Panagiotakos DB, Pitsavos C, Chrysohoou C, Stefanadis C. Associations between coffee consumption and in - flam ma tory mark ers in healthy per sons: the ATTICA study. Am J Clin Nutr Oct;80(4): Zeegers MP, Tan FE, Goldbohm RA, van den Brandt PA. Are cof - fee and tea con sump tion as so ci ated with uri nary tract can cer risk? A sys tem atic re view and meta-anal y sis. Int J Epidemiol Apr;30(2): Vol. 16 No. 1 Medical Herbalism Page 11

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