An Evidence-Based Guide to Herb Safety During Pregnancy & Lactation Jillian Bar-av, MS, RH(AHG), CNS [email protected] www.greenspringherbs.com 410-258-9625 Should herbs be used during pregnancy and lactation? • Some say no • Some say yes • Some say only if the benefit outweighs the risk What do we mean by herb use? • Herbs in food • Beverage herbal teas • Herbs as medicine Dosage • Even herbs that are considered safe and used as spices have dosage restrictions: • • • • • Peppermint Ginger Garlic Cinnamon Turmeric • Pregnant woman’s physiology is different from non-pregnant woman – Due to cardiovascular and renal changes, she is able to see benefit from smaller doses Not all stages of pregnancy and lactation are the same • Cautions necessary in 1st trimester due to fetal development of central nervous system can be relaxed in later trimesters • Cautions necessary in early lactation can also be relaxed later on Product quality • No matter what herb is being taken while pregnant or breastfeeding, the quality must be known • Products that have been adulterated can obviously be dangerous Hairy Baby Case • A woman thought she was taking ginseng throughout her pregnancy • She was taking 2x the suggested dose on the label • She developed signs of androgenization • The baby was born with significant hirsutism • It was reported as a ginseng adverse effect • The label showed that the product actually contained Siberian ginseng (Eleutherococcus senticosus) • The product was also adulterated with Periploca sepium, although in vitro studies did not show it to have androgenic activity Prudent Practitioner Guidelines • Avoid herbs during 1st trimester – Including most fertility herbs – beverage/nutritive teas and herbs as spices/seasoning are generally ok • Only use herbs when the benefit outweighs the risk – Examples • • • • When medication would be riskier to fetus than herbs Health of mother is jeopardizing health of fetus Miscarriage prevention Medication would mean early weaning Purpose of the Guide • Create a guide that is actually useful for practitioners – Warnings to use “only under the guidance of a qualified practitioner” are useless to practitioners – We are the practitioners! • Though we also need to understand our limitations Principles of the Guide • Err on the side of caution, but allow for flexibility • Blend information from the most reputable sources on the subject – scientific findings – traditional use – clinical experience of modern herbalists/midwives Rating System of the Guide • Simple, clear, easy to use at-a-glance • Categories are for actual use – Safe – Restricted use – Contraindicated • Clear reasons for ratings with references Ratings distinguish between pregnancy & lactation • Often sources will say “contraindicated during pregnancy and lactation due to hormonal influences” – What type of hormonal influence? – If it is oxytocic, would it really be contraindicated in both pregnancy and lactation? • Oxytocin is the hormone responsible for labor induction and therefore oxytocic herbs should be avoided during pregnancy, unless being used to assist labor • Oxytocin is also the hormone responsible for the milk ejection reflex (MER), therefore herbs that influence oxytocin may be indicated as galactagogues Ratings Ratings: Disagreements • If sources disagreed on the safety of the herb, it was usually given a P2 or L2 rating • In some cases a choice was made to rate the herb as safe or contraindicated even when sources disagreed – Based on quality of evidence – Peer practitioner feedback • Contradictory information is always included P2 & L2 Ratings 1. Unsafe for internal use, but safe for external use 2. Unsafe during 1st trimester, but can be used in later pregnancy 3. Herbs that are only used during labor 4. Herbs that are only used for miscarriage prevention or pre-term contractions 5. Unsafe during early breastfeeding, but safe for later stage breastfeeding 6. Lack of data 7. Practitioner judgment required Methodology • Each herb was looked up in each of 13 sources • Information from one source may not have been included if: – information from one of the other sources obviously surpassed it in thoroughness and accuracy – it was referencing one of the other sources American Herbal Products Association’s Botanical Safety Handbook Michael McGuffin, Christopher Hobbs, Roy Upton, Alicia Goldberg • In the absence of information herbs are categorized as “Class 1: herbs that can be safely consumed when used appropriately” • Published in 1997 • Distinction between pregnancy & lactation is made • Very comprehensive in terms of number of herbs listed The Essential Guide to Herbal Safety by Simon Mills & Kerry Bone • Distinction between pregnancy & lactation is made • In depth information on each herb with rationale and references • Pregnancy ratings: A, B1, B2, B3, C, D, X • Lactation ratings: ND, C, CC, SD, X • Appendix includes herbs in list form Herbal Contraindications and Drug Interactions Plus herbal adjuncts with medicines, Fourth edition By Francis Brinker, N.D. • 4th edition, published 2010 • Easier format than previous editions • More explanations, especially of warnings based on in vitro evidence • Extremely cautious ratings • This source often contraindicates herbs with pregnancy that other sources do not • References are online, as well as updates Botanical Medicine for Women’s Health by Aviva Romm • Best information regarding clinical experience • Comprehensive chart in back with safety info • Only a few full monographs, so some hunting by subject is required to find all the info on individual herbs • Published 2010 American Herbal Pharmacopoeia monographs by Roy Upton • Extremely well-researched • Publishing dates vary from 1997 to 2012 • 29 monographs • PDF = $39.95, Paper copy = $44.95 Herbs & Natural Supplements An evidence-based guide by Lesley Braun & Marc Cohen • Safety ratings are middle of the road • Sometimes references secondary literature, like Mills & Bone, sometimes actual studies The ABC Clinical Guide to Herbs by Mark Blumenthal • Published 2003 • Only about 30 monographs • Tends to reference Commission E, Brinker, AHPA for pregnancy/lactation info A Clinical Guide to Blending Liquid Herbs By Kerry Bone • Ratings are very succinct, explanations are short • In the absence of evidence, it rates herbs as “no adverse effects expected” • On the lenient-side • Published prior (2003) to The Essential Guide to Herbal Safety (2005) Clinical Applications of Ayurvedic and Chinese Herbs by Kerry Bone • Source for Ayurvedic and Chinese herbs • Does not specifically outline pregnancy/lactation safety • Published 1996 Native American Ethnobotany by Daniel Moerman • Primary source for Native American use • Can lead to source for “traditional use” information • Will not contain warnings based on modern understanding King’s American Dispensatory, 1898 by Harvey Wickes Felter & John Uri Lloyd • Source for Eclectic physician use • Often the primary source of “traditional use” information • Clinical use is very descriptive www.naturaldatabase.com • $10/year subscription • Online, so it is kept updated • Everything is referenced / hyperlinked if applicable • Extremely cautious ratings • Almost every herb says “insufficient reliable information, avoid use” • Almost every herb has a listing www.naturalstandard.com • Well referenced with hyperlinks to articles • Online, so it is kept up to date • Often provides more information than Natural Medicines Comprehensive Database, though conclusions are also extremely cautious • Expensive, this will limit access for most people P1 & L1 Ratings • Even the safest of herbs all have at least 1 source that lists it as unsafe or unknown • Herbs commonly accepted as safe during pregnancy listed in Aviva Romm’s book: – – – – – Red raspberry Spearmint Chamomile Lemon balm Nettles Chamomile P1 • known safe, but commonly cited as contraindicated during pregnancy • 1979 study that found teratogenic effects using high doses of a concentrated extract of alpha-bisabolol (oil constituent found in chamomile) • lower doses were not shown to be teratogenic •It would not be possible to drink enough tea to approximate the teratogenic dose of this constituent Lemon balm P2 • Listed as safe by AHPA, Romm, and Bone – Romm suggests it as a safe choice for insomnia during 3rd trimester, but to avoid with thyroid conditions/medications • But Brinker says to avoid during pregnancy – Emmenagogue effects (empirical) – Antithyrotropic (in vitro) and antigonadatropic (animal studies) L1 • compatible with breasfeeding • essential oil may pass into breast milk, producing a mild sedative effect in the baby Mills & Bone Category A herbs No proven increase in the frequency of malformation or other harmful effects on the foetus despite consumption by a large number of women • • • • • • Bilberry fruit Chamomile Cranberry Echinacea Garlic Ginger • • • • • Turmeric Raspberry leaf Licorice* Senna* Ginseng* *Safety issues exist (Romm) Licorice P2 • Large amounts (500mg glycyrrhizin or greater per week) – Associated with pre-term & early term delivery in humans – 1049 Finnish pregnant women tracked their licorice candy consumption and were grouped into 3 groups • Low = less than 250mg glycyrrhizin per week • Moderate = 250-499mg • Heavy = more than 500mg Am. J. Epidemiol. (2001) 153 (11): 1085-1088. • Heavy consumption doubled the risk of giving birth before 38 weeks • No effect was seen on maternal blood pressure – European authorities advise it is likely safe in doses up to 3g/day (Mills & Bone, 2005) Garlic and pregnancy P1 • A small clinical trial observed that garlic ingestion by pregnant women significantly alters the odor of their amniotic fluid • Garlic has been noted on more than one occasion on the breath of newborn Pakistani infants • Precautions about dosage are cited by multiple sources – Large doses of fresh raw garlic or allicin-releasing products should not be consumed during pregnancy to avoid bleeding complications Garlic anticoagulant concerns P1 • A single case report exists for an 87 year old man who developed platelet dysfunction after chronic consumption of 2g/day fresh cloves • 5g/day fresh garlic is contraindicated with warfarin – 2 cases of stabilized patients on warfarin whose INR increased and clotting times doubled after intake of garlic products (garlic oil and garlic tablets) Garlic anticoagulant concerns P1 • several cases of bleeding complications during surgery associated with garlic intake – A 2002 report of odorless garlic tablets taken regularly, including 5 taken the day before surgery (equivalent to 5g fresh bulb) resulted in hemorrhage – 1995 “heavy garlic intake” before cosmetic surgery resulted in bleeding complications and prolonged bleeding time Garlic and Lactation L1 • Used as a galactagogue in India – Small placebo-controlled study showed: • garlic ingestion significantly and consistently increased the perceived intensity of the milk odor • which peaked in strength 2 hours after ingestion • babies detected theses changes, as indicated by: – increased time of attachment – more suckling – tendency to ingest more milk • a follow-up study showed that the novelty wore off as infants got accustomed to the flavor and they returned to their usual feeding patterns Garlic and topical use • Should not be used topically! – Not safe for baby to be exposed to it directly • Internal use by the mother in cases of breast candidiasis may be useful Fertility herbs • Herbs used for fertility are not necessarily safe to continue once pregnancy has been achieved Shatavari P3 • Traditionally used as an abortifacient • If using to promote fertility, it should be discontinued when pregnancy is achieved L1 • Compatible with breastfeeding • Used in Ayurveda to promote lactation (1g/day) Chamaelirium (False Unicorn Root) P3 • Considered helpful in amenorrhea and difficulty conceiving • Not a traditional use by Native Americans or Eclectics – Eclectics used it for “uterine weakness in which relaxation of the tissue is so great as to give the sensation of downward pressure, dragging or expulsion…a sensation as if everything from the pelvis would fall out or be expelled” • Popularized as a fertility agent by modern herbalists • Listed as abortifacient by AHPA • No safety data exists for its use during pregnancy and it has been shown to possess uterine stimulant activity (empirical) L1 - compatible with breastfeeding Concerns during Pregnancy • Ist trimester: – Nausea/Vomiting – Miscarriage prevention – Urinary tract infections • 2nd trimester: – Heartburn / Reflux – Iron deficiency anemia 3rd trimester concerns • • • • • • • Constipation Varicosities Insomnia Hypertension / Preeclampsia Group B strep Uterine irritability / Pre-term labor Labor - delayed labor, rigid cervix, ineffective contractions, fatigue, pain, anxiety Vitex P2 • Often used for amenorrhea and to regulate irregular cycles • Used to prevent miscarriages • Ideally given for 3 months prior to conception and continued past the date of previous miscarriage • Thought to be progesterogenic via its affects on prolactin Ginger P1 • Most popular self-medication among pregnant women • Generally recommended not to exceed 1g/day due to emmenagogue concerns • Multiple studies on ginger for nausea & vomiting during pregnancy suggest up to 2g/day of dried root is safe and effective • AHPA lists fresh root as class 1, but dried root as contraindicated during pregnancy • It was contraindicated by Commission E based on in vitro research on single compounds – Of course leading to other sources to list as contraindicated L1 - compatible with breastfeeding Cramp bark / black haw P1 • Long history of use by Western herbalists and Native Americans as a spasmolytic for threatened miscarriage • Officially listed in the United States Pharmacopoeia in 1882 • It’s use as an antispasmodic and preventative for miscarriage was popularized by the Eclectic physicians • Small doses were considered excellent by the Eclectics to ease irregular contractions and “greatly facilitate a speedy and uncomplicated labor” • Still widely used by contemporary midwives and herbalists during labor to arrest uterine spasm when there is uterine cramping without cervical dilation and protracted early labor Uva Ursi P2 • 2 decades of use among midwives for acute cystitis during pregnancy has resulted in no adverse reports • Use during 1st trimester should be limited to 4 days – Concern about potential to stimulate uterine contractions cited by secondary sources – This concern does not reflect actual reports or clinical observance – UTIs alone can cause uterine contractions Uva Ursi and hydroquinone P2 • Uva ursi contains arbutin which is metabolized into hydroquinone • Hydroquinone has been shown to be toxic to humans in large amounts (industrial handling exposure) • It is used in black & white film development and is a controversial ingredient in beauty products as a skin lightener Uva Ursi and hydroquinone P2 • These reports have led to theoretical warnings that uva ursi is toxic in general, and especially during pregnancy – Hydroquinone has been shown to have mild negative affects on reproduction in rats • • • • Reduced maternal weight gain decreased fetal weight increased resorption reduced male fertility (www.epa.gov) Uva Ursi and hydroquinone P2 • Concerns regarding fetal toxicity of hydroquinone appear to be exaggerated • At a maximum dose of 12g, at a minimum expected concentration of artbutin of 12%, at 100% solubility and absorbability, the highest potential hydroquinone concentration per full daily dose would be 1440mg – well below the established NOEL (no observed effect level) of 5250mg of pure hydroquinone daily • Upton, R. American Herbal Pharmacopoeia and therapeutic compendium. Uva Ursi and Dosage P2 • Case report of one woman who consumed uva ursi regularly for 3 years who developed bulls-eye maculopathy • This was likely due to the inhibition of melanin synthesis since arbutin is metabolized to hydroquinone which is known to inhibit the enzyme tyrosine kinase involved in synthesizing melanin Brinker, F. (2010). Herbal contraindications and drug interactions. Uva ursi and Lactation L2 • No studies on Uva ursi in lactating women • Hydroquinone was studied on lactating rats and no toxicity was found • Use during lactation is strongly discouraged by Mills & Bone due to arbutin/hydroquinone caution • Aviva Romm suggests use during lactation is possible if a low dose is used and the infant is closely monitored by a qualified health practitioner Horse Chestnut - varicosities P2 • High doses given to rabbits decreased fetal weight gain • But clinical studies to treat venous conditions in pregnant women at doses of 600mg (containing 100mg aescin) for 2-4 weeks have been successful L2 - compatible with breastfeeding, but use caution Insomnia and pregnancy • Chamomile - P1 • Lavender - P1 • Skullcap - P1 – Eclectic texts indicate that a concentrated preparation of skullcap was combined with other nervines and spasmolytics for various female disorders in both pregnant and non-pregnant women – Source is important to avoid adulteration with germander Insomnia and pregnancy • Lemon balm - P2 • Valerian - P2 • no problems were noted in 3 cases of intentional overdose with 2-5g of valerian during weeks 3-10 of pregnancy • valerian is one of the most commonly used herbs during pregnancy and was not associated with any negative outcomes – though it is not recommended due to theoretical concern over teratogenic effects of valepotriates – Valepotriates have been shown to be cytotoxic and mutagenic in vitro – however valepotriates degrade rapidly and are typically not found in commercial preparations • Passionflower - P2 Red Raspberry Leaf P1 • • • One of the most historically venerated herbal uterine tonics Recommended by herbalists/midwives as an infusion, 1-3 cups daily Of all the herbs that might be considered for labor preparation, red raspberry appears the safest – Used to strengthen the uterus, improve labor outcome, prevent excessive bleeding – 1 study indicates 63% of US midwives use to stimulate labor • though it does not appear very effective at stimulating labor – 1 study showed a reduction in length of second stage labor and reduction of delivery by forceps – Another study showed a reduced rate of pre and post-term gestation and reduced need for obstetric interventions including csection, forceps delivery, amniotomy, and vacuum extraction Red Raspberry Leaf, minor cautions P1 • Can cause nausea in 1st trimester due to astringency (Romm) • Best to restrict use to 2nd & 3rd trimesters (Braun, Bone) • Avoid in history of labor that comes on suddenly, hard, fast, and strong due to uterine stimulant activity (in vitro) (Brinker) • 1 case of a pregnant woman who discontinued use after experiencing increased Braxton-Hicks contractions, however causality was not confirmed (Mills & Bone) – Suggested to slowly increase dose over a period of weeks to reduce chance for Braxton-Hicks contractions (Denise Tiran, 2003) • Pharmacological experiments have yielded conflicting data on uterine contraction and relaxation, but overall results imply a regulatory action on contractions (Mills & Bone) Black cohosh P2 • Avoid during 1st trimester (though potentially useful for threatened miscarriage) • Emmenagogue • Used by Cherokee to stimulate menstruation • Its influence on hormones is still not understood • Reports of hepatotoxicity • Historical use as a partus preparator – This is what led to modern contraindications during pregnancy Eclectic use during pregnancy P2 • Eclectics used for: – Threatened miscarriage – Premature labor – Relaxation of the os uteri during labor – Often in combination with Viburnum prunifolium • Eclectics also used it: – During labor when the pains are “inefficient, feeble, or irregular to stimulate normal action” and it was deemed an excellent partus preparator when given for several weeks before birth Kings, 1898 Used to reduce and promote uterine contractions? P2 • Dosage – Low doses were used for threatened miscarriage – Higher doses were used to induce labor • Current use in midwifery: – assist labor in fairly low doses, often combined with other herbs – prevent threatened miscarriage Safety during Eclectic use P2 • Widespread use by Eclectics during pregnancy • Thousands of case reports • Very few adverse effects noted – Cook reports in 1869 a rare case of threatened abortion while it was being used during pregnancy – In I919, Ellingwood reports 6 cases of severe uterine hemorrhage following its use during labor Safety recommendations today P2 • The prudent practitioner should avoid the use of black cohosh during pregnancy • Except for use during labor to relieve pain and spasmodic uterine contractions associated with dysfunctional labor Aviva Romm. Botanical Medicine for Women’s Health, 2010. Black Cohosh and Lactation L3 • Mills & Bone and Romm strongly discourage its use while breastfeeding • Lack of data – Don’t know its affect on breastfeeding babies – Or its effect on lactation • Studies on its effect on estrogen are contradictory • More recent studies suggest it has no estrogenic effect Black Cohosh and Lactation L3 • Used by the Iriquois to “promote the flow of milk in women” (Moerman, 2000) • Does not seem to effect prolactin, but this has not been studied in lactating women • Not contraindicated during lactation by German Commission E or AHPA Blue Cohosh - history P3 • Historical use as a partus preparator and to induce labor • Used to promote childbirth by the Cherokee and Potowami • The only specific information on how it was used by Native Americans was offered by the “Indian Doctor” Peter Smith in 1813: • He claimed it was used for 2-3 weeks prior to delivery as well as during labor • This use was popularized by the Eclectics who added specific indications • It was used “to relieve false labor pains and thought to be most valuable to coordinate and strengthen contractions in prolonged labor due to debility and fatigue where the tissues feel full, as if congested” Blue Cohosh - history continues P3 • Late 1800s / early 1900s • Added to United States Dispensatory • Added to United States Pharmacopoeia • Early 1900s • Use declines as herbs fall out of favor • 1978 • Its use as an emmenagogue & uterine tonic are popularized by Jeannine Parvati-Baker in Hygieia • 1986 • Use during childbirth is promoted by Susun Weed in Wise Woman Herbal The Childbearing Year • 1990s • Blue cohosh is among the most widely used herbs for assistance in labor Blue Cohosh - safety concerns arise P3 • 1996-1998 • 3 case reports appear in the literature suggesting severe adverse neonatal outcomes associated with maternal ingestion of blue cohosh including: – – – – – – focal motor seizure myocardial infarction ischemic stroke multi-organ hypoxic injury permanent central nervous system damage profound congestive heart failure Blue Cohosh Gunn and Wright Case Report, 1996 P3 – Combination of Blue and Black Cohosh administered to a 41.6 weeks pregnant woman to attempt labor induction – Baby girl was born unable to breath spontaneously – Midwives proceeded to deliver CPR for 30 minutes – Baby gasped and was transferred to hospital where she required mechanical ventilation – Infant had seizures and was diagnosed with kidney and brain damage – Authors of the case report suggest the hypoxic-ischemic damage was due to myocardial toxicity secondary to blue cohosh – Though they do question if inadequate resuscitation was a possible factor Blue Cohosh Jones and Lawson Case Report,1998 P3 – 36 yr. old mother of 3 children gave birth to a boy at 41 weeks – She took 1 blue cohosh tablet (otherwise unspecified) 3x/day for 3 weeks prior to delivery – During that time she noticed: • increased uterine activity • decreased fetal movement Blue Cohosh Jones and Lawson Case Report,1998 P3 • 20 minutes after delivery baby developed respiratory distress, acidosis, ischemic hepatitis, and shock • He was intubated, given mechanical ventilation and moved to neonatal intensive care • He was diagnosed with enlarged heart and with having had a myocardial infarction • No signs of infection or congenital cardiac anomoly existed to explain the condition • At 2 yrs. old the child remained on digoxin therapy Jones and Lawson - Case Discussion P3 • The authors concluded that presentation of cardiogenic shock and MI were consistent with the known pharmacology of blue cohosh • Although causality cannot be definitively established, it demonstrates the most plausible case for relationship between blue cohosh use and a neonatal ischemic event – Case is comprehensive, generally allowing other causes to be excluded – Although blue cohosh product was not authenticated, dose, duration of use, and form are provided Jones and Lawson - dosage issues P3 • The crude herb as would be found in capsule or tablet contains more saponins than would be found in a tincture – Saponins have been associated with uterine stimulant activity – Thought to be responsible for cardiotoxic effects on newborns • 3x the suggested dose on the label was used Jones and Lawson - conclusions P3 • Decreased fetal movement could have been a signal of placental insufficiency • Fetal complications begin to increase after 41 weeks gestation • Cardiomegaly could have been due to either the blue cohosh, placental insufficiency, or a combination of the two Blue Cohosh - research P3 • Research into mechanisms of action find: – embryotoxic and teratogenic alkaloids • anagyrine and baptifoline – Saponins are thought to be responsible for uterine stimulation Blue Cohosh - current recommendations P3 • Consensus to discontinue its use during all phases of pregnancy – If it is to be used during labor: • Only the tincture should be used • Only under supervision of qualified maternity health professional • Proper fetal and neonatal monitoring (not for use in homebirth) Should herbs be used during lactation? What are the potential benefits? • Enhanced milk production • Galactagogues have a long history of traditional use • In the Netherlands, anise seed cookies are a traditional gift given to new mothers • 85% of Indian mothers who are breastfeeding will consume large amounts of fenugreek in the form of a traditional food called methipak to act as a galactagogue and general strengthening tonic • Address health concerns of the mother while avoiding pharmaceuticals • Is the mother being told to wean so that she can take a pharmaceutical? Should herbs be used during lactation? What are the concerns? • Adverse effect on infant – What are the potential effects of the herb being taken? – – – – How old is the baby? Is the baby exclusively breastfeeding? Is the baby eating other foods? Is it a toddler with minimal nursing habits? • Adverse effect on lactation • Galactagogues are not always desirable • Will the herb dry up milk supply? • Is it for external use on the breast? • Potential for baby to ingest directly Lactation Do phytochemicals enter the milk? • Foods in the mother’s diet can obviously affect the baby – Cruciferous vegetables • Cause crying & colic – Coffee & Chocolate • Act as stimulants Lactation Considerations • Bioavailablity – Must be absorbed into bloodstream to get into breast milk – If in the bloodstream, usually only 1% will enter breast milk – Some exceptions can enter breast milk up to 10% – Less than 10% is usually too small to have a pharmacological effect Iodine & Alkaloids • Most chemicals do not get sequestered in breast milk, with a few exceptions: – Iodine is actively transported into breast milk • Too much potassium iodide can cause hypothyroidsm in infants • If there is contamination with radioactive iodine 131, potassium iodide should be taken by a breastfeeding mother at a dose of 130mg/day if recommended by government agencies • Same as above for pregnant women www.infantrisk.com (Thomas Hale Ph.D) – Alkaloids (weakly basic) concentrate in (slightly acidic) breast milk Protein binding • Substances bound to proteins are not free to diffuse into breast milk – Ex. Coumadin is 99% bound to serum proteins – Miniscule amount gets into breast milk – No consequence to infant Size of molecules • Large molecules do not enter breast milk – Insulin – Heparin (injectable anticoagulant) • Very small molecules enter breast milk – Ethanol – Volatile oils Lipid solubility • Lipid soluble chemicals enter breast milk more easily – Higher than expected levels can occur – Ex: fluoxetine (prozac) • One study found larger concentrations of fluoxetine in post-feeding breast milk than prefeeding breast milk • Lipid concentration of breast milk increases during feeding First days of nursing • Enhanced bioavailability of chemicals during colostrum production • Junctures between cells allow immunoglobulins in the bloodstream (as well as other chemicals) entry into colostrum during first 3-10 days of breastfeeding Age & weight of infant affect elimination capacity • Newborn – Immature gut, liver, kidney function • 2 weeks – Liver more developed, jaundice disappears • 4-5 months – Kidney clearance capacity fully developed Studies on lactation & pharmaceuticals • The amount of drug entry into the milk is usually only studied during one stage of feeding • Few drugs have been studied over the long term of weeks or months of exposure • Despite this lack of information, there are very few reported adverse reactions – while there are increasing numbers of mothers taking pharmaceuticals while breastfeeding • Predictions are made based on how drugs are metabolized by the mother Studies on lactation and herbal medicines • Assessment is hindered by lack of information about – Bioavailability – Serum levels – Half life – Protein binding Lactation and herb risk • Despite a lack of information – Very few cases of adverse reactions are documented involving ingestion of phytochemicals via breastfeeding – 1 case of infant death • Mother used both coltsfoot and petasites both during pregnancy and while breastfeeding • Both contain toxic pyrrolizidine alkaloids • PAs cause irreversible liver damage Galactagogues • Galactagogues stimulate the production or flow of breast milk • They may act hormonally • They may act as nutritives to improve milk quality and quantity • Nervines are often combined to encourage relaxation and promote milk let down Herbal Galactagogues Galactagogues • • • • • • • • • • Marshmallow root Dill Oats Caraway Blessed thistle Fennel seed Goat’s Rue Barley Hops Anise seed (not to be confused with • • Fenugreek Chaste Tree Berry Star Anise which is associated with toxicity) Nervines/Anxolytics to promote milk let-down • • • • • Hops Lavender Motherwort Chamomile Blue Vervain Aviva Romm. Botanical Medicine for Women’s Health, 2010. Lactation & Prolactin • Initial production of milk is driven by high serum prolactin levels in the mother • Prolactin levels rise in response to each feeding • Later, each breast independently produces milk in response to milk removal • Prolactin levels are near normal between nursing sessions with spikes after each feeding • Frequent & high prolactin spikes are associated with – Good milk supply – Maintenance of lactation amenorrhea Fenugreek L1 • Traditional use as a galactagogue • Can create a maple syrup-like smell to baby’s urine, but should not be confused with maple syrup urine disease • No controlled studies • 10g/day significantly increased milk yields in goats • In India a traditional food called methipak, made of wheat, fat, sugar, and generous amounts of fenugreek, is used by 85% of lactating mothers (1985 survey) • Said to act as a galactagogue, strengthener, and reducer of body aches • Used during last 1-2 months of pregnancy • And from 10 days post-partum for 1-2 months • Common to consume of 50g methipak in the morning Chaste Tree Berry & Lactation P2 • Only herb with studies on human lactation – 2 clinical trials done in the 1950s showed that chaste tree increased milk supply of nursing mothers – Despite methodological flaws, the findings consistently showed a galactagogue effect of the herb Vitex and Prolactin P2 • in vitro evidence and 1 rat study show prolactin-inhibition, suggesting that chaste tree inhibits lactation • one reason it is listed by some sources as contraindicated during lactation • This information directly opposes its use as a galactagogue (and historical use by monks to reduce libido) • Differences in results could be due to: • • • • dosage used differences between human and rat physiology character of the extract administered route of administration (oral vs. injected) Vitex may have a dose-dependent effect on prolactin P2 • Males were given differing doses of chaste tree: 120mg, 240mg, 480mg, & placebo • The lowest dose of 120mg showed a stimulating effect on prolactin levels • The middle dose of 240mg showed no effect • The highest dose of 480mg showed an inhibitory effect Why would this be? • Need to understand the relationship between dopamine and prolactin • Dopamine is both a neurohormone and neurotransmitter • When dopamine is released from the hypothalamus, it acts like a hormone and has an inhibitory effect on prolactin release from the pituitary Dopamine secreted by the hypothalamus inhibits prolactin release from the pituitary Hypothalamus Dopamine = prolactin-inhibiting factor Anterior Pituitary Decreased Prolactin release Vitex has been shown to be dopaminergic • Vitex has affinity for dopamine D2 receptors in vitro • Diterpenes have been implicated as active constituents interacting with dopamine receptors • Dopaminergic activity decreases prolactin release • This is why vitex is thought to be useful in: • Hyperprolactinemia • Corpus luteal deficiency, which can lead to progesterone deficiency • PMS • Amenorrhea • Premenstrual mastalgia Low dose Vitex Higher dose Vitex Hypothalamus Dopamine Inhibition Dopamine Stimulation Anterior Pituitary Increased Prolactin Decreased Prolactin How does Vitex affect progesterone? • Rat studies have shown that prolactin increases progesterone by maintaining the structure of the corpus luteum after mating, thereby increasing progesterone release (Freeman et al, 2000) • Logically, in order for chaste tree to increase progesterone, it would have to increase prolactin – The only way it could do that is if it was inhibiting dopamine, not stimulating it Topical use of herbs during lactation • Herbs used on the body, but not on the breast, are generally considered safe while breastfeeding • Herbs used on the breast must be safe and non-toxic to the baby • Baby should be nursed prior to application of anything to the nipple and nipples should be rinsed before feeding – Do not want baby to develop aversion to the breast due to bitter taste Concerns about topical application to breasts • The skin of the areola is very thin compared to other skin on the body – Very sensitive • higher chance of allergic reaction – Substances more easily absorbed through it and into the breast – Wiping away potentially toxic herbs before nursing may not be enough – It is possible that substances applied to the breast will be absorbed into the breast tissue and enter milk ducts in relatively large amounts • Comfrey should be avoided due to PAs • Essential oils should be avoided, including tea tree oil, which has had 2 cases of known toxicity via oral ingestion St. John’s Wort & pregnancy • Strong evidence that SSRIs taken during pregnancy cause neonates to suffer withdrawal symptoms P2 • St. John’s Wort is not contraindicated during pregnancy, but safety studies are lacking • Used by the Cherokee with other herbs to promote menstruation (Moerman, 2000) • High doses show reduced litter sizes and smaller offspring in mice • Case report of a 38 yr. old pregnant woman taking 900mg SJW 6:1 extract from 24 weeks until 24 hours prior to delivery • resulted in a healthy baby • mother discontinued SJW postpartum and initiated breastfeeding • the neonate developed jaundice on day 5, mother resumed SJW on day 20 (300mg) and continued breastfeeding • behavioral assessment at 4 and 33 days was normal SJW & pregnancy P2 • 2009 prospective cohort study conducted by Motherisk, Hospital for Sick Children, Toronto, Canada – – – – 54 pregnant women exposed to SJW 54 pregnant women on antidepressant meds 54 pregnant women with no teratogenic exposure Results showed no major malformations across the 3 groups (5%, 4%, 0%) • (major malformation rate across general population is 35%) Jean-Jacques Dugoua, 2010 St. John’s Wort and lactation L1 • 300-480mg SJW/day has shown low levels of hyperforin excreted into breast milk • No side effects seen in infants • The plasma of one infant whose mother was taking 300mg/day showed no detectable constituents • Thomas Hale, lactation & medication expert, suggests that the transfer to milk of SJW is minimal and it appears safe during lactation Sources 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 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