Abstract
Plant products have been used to facilitate lactation around the world since time immemorial. Fifty-four plant-based galactogogues are reviewed in LactMed, but that number only scratches the surface. In a recent survey, about 28% of nursing mothers in the United States reported consuming herbal galactogogue supplements to increase milk supply. 1
Very few herbal galactogogues have undergone rigorous scientific scrutiny. Common design flaws in the studies that do exist include failure to define the products being tested, use of multi-ingredient mixtures, lack of blinding, lack of placebo control, failure to define the study population, inappropriate endpoints, and failure to use intention-to-treat analysis.
To be fair, galactogogue studies are extremely difficult to design and conduct well. Even the best studies with pharmaceutical drugs known to reliably increase serum prolactin, such as domperidone, have not had perfect designs. One issue is patient selection. Should the study participants be every person who delivers, only primiparous patients, only those who deliver a preterm infant, only those who deliver by cesarean section, or only those whose milk supply is low at a certain point in time? And if so, when?
The education of mothers about breastfeeding technique is extremely uneven in studies. Sometimes mothers of both study drug and placebo are given the same instruction, and in other studies, those receiving the study drug are given more education. In other studies, education is not mentioned. The content and quality of education also vary from study to study.
A strong placebo effect is likely to occur in galactogogue studies. For example, in a recent survey, “sports drinks” and coconut milk or water were reported by mothers to increase milk supply almost as well as fenugreek, but 5% of mothers stated that fenugreek decreased milk supply while none reported a decrease with the drinks. 1
It is not entirely clear what the endpoint of a galactogogue study should be. The point of taking a galactogogue should be to provide enough nutrition for the infant to thrive. However, many studies measure only differences in milk production over time without any consideration of whether the amount of milk is adequate for infant nutrition. Milk production is often measured by using an electric breast pump to completely drain the breast. Term infants typically drain about 67% of milk on average, whereas a hospital-grade electric pump can remove greater amounts. 2 The excess production that is measured in treated women by pumping may be clinically meaningless because untreated mothers may be producing adequate amounts of milk without the galactogogue.
Follow-up of infant growth is more difficult than measuring milk output in hospitalized patients or upon hospital discharge, so many studies do not follow the infants. An intermediate outcome is asking mothers at various times whether they are still nursing and what percentage. This method is subject to participant bias and perhaps over-reporting to please investigators.
Herbal supplements have the added difficulties of a lack of standardization of content (if the active ingredients are even known), making dosage selection problematic. Furthermore, masking the active drug can sometimes be difficult. For example, fenugreek can give urine the odor of maple syrup. Other herbals have strong flavors, aromas, or colors that can be detected by study subjects, potentially unblinding the study.
Another issue is the availability of products that are identical or similar to those used in studies from outside of the country where they were studied. Many articles report the use of products that are either compounded locally or are available only in a specific country’s market. Products in another country could be quite different. A related issue is the use of highly purified derivatives. One study on a high dose of the highly purified milk thistle component silymarin indicated some galactogogue activity. This finding does not necessarily imply the activity of milk thistle itself, which has lower and variable levels of silymarin.
These standardization problems are in part a by-product of the lack of regulatory oversight of herbal products by the Food and Drug Administration (FDA) or other regulatory agencies. Only after contamination of herbals by foreign drugs or substances (e.g., heavy metals) is discovered, which is not infrequent, is the FDA allowed to remove herbals from commerce under current law.
Some studies of herbal galactogogues have been conducted in developing countries in patient populations that may have inadequate diets. Providing participants with nutrient-rich supplements might help them meet the additional nutritional requirements needed during lactation. The results of these studies are not necessarily translatable to mothers in developed countries with adequate nutrition.
A common problem in most studies is the small number of participants, typically less than 100. Most studies on herbal galactogogues lack the statistical power to determine differences between the herbal and the comparator.
Possible Mechanisms of Action
Increasing serum prolactin is often proposed as a mechanism for the increase in milk supply by galactogogues. Indeed, pharmaceutical galactogogues such as domperidone and metoclopramide work this way. Some studies have documented increases in serum prolactin in excess of placebo from herbal products such as wild asparagus (Asparagus racemosus). Interestingly, studies have shown no increase in serum prolactin in nursing mothers with fenugreek seeds or fennel, although this has often been mentioned as their mechanism of action. Another proposed mechanism is that herbal components might act as direct stimulants to prolactin receptors, bypassing an increase in serum prolactin. However, there is no relationship between the concentration of prolactin in the plasma and the rate of milk synthesis in either the short or long term.2–4
Although estrogens are important during pregnancy to prepare the breast for lactation, estrogen can suppress lactation postpartum. Somewhat counterintuitively, many purported herbal galactogogues have estrogenic activity in animal assays. A possible explanation of galactogogue activity is that the estrogenic activity of these herbals is weaker than endogenous estradiol. If estradiol levels are so high postpartum that they are suppressing lactation, a weak estrogen could theoretically compete at estrogen receptors to lower overall estrogenic stimulation. Isoflavones found in foods such as soy are examples of phytoestrogens.
Another proposed mechanism is antioxidant and chemoprotection by polyphenols that are found in many herbal galactogogues. Lactation is a period of high energy demand and enhanced mitochondrial function that is associated with the generation of reactive oxygen species. Many herbals are rich in polyphenols that can potentially protect mammary epithelial cells from these reactive oxygen species through their antioxidant and anti-inflammatory properties. 5
Other mechanisms that have been proposed are histamine-induced prolactin release, or serotonin-induced release of thyrotropin-releasing hormone for stinging nettle (Urtica dioica) and sensitization of mammary epithelial cells to insulin for goat’s rue (Galega officinalis).
Some traditional products from overseas are now showing up in supplements in the United States and other western countries. The following purported herbal galactogogues are illustrative of the various proposed mechanisms and study design shortcomings. Further information on the specific herbals used during breastfeeding can be found in LactMed, where the original references are reported.
Asparagus racemosus
Asparagus racemosus (wild asparagus), commonly called shatavari, has a long history of use as a galactogogue in India and is included in the official ayurvedic pharmacopeia for this use. It is a different plant from the asparagus commonly used as a food (Asparagus officinalis). The root of wild asparagus contains shatavarins and flavonoids that have anti-inflammatory and antioxidant properties. It also contains steroidal saponins that have phytoestrogenic activity, although the active galactogogue components have not been elucidated. The safety of wild asparagus has not been rigorously studied, but small clinical studies found no adverse effects in mothers or their nursing infants. Two small but relatively well-performed studies found galactogogue activity in wild asparagus.
One double-blind controlled study gave shatavari 300 mg or placebo three times daily for 30 days. At the end of the study, the serum prolactin in the treatment group was three times higher than in the placebo group. Infant weights increased more in the treatment group (16% versus 6%), and treated mothers rated their satisfaction and their infants’ happiness greater than those in the placebo group. The study had a dropout rate of about 15% but was analyzed per protocol rather than intention to treat. Per-protocol analysis tends to exaggerate the efficacy of the active product.
A second controlled study found that mothers who received A. racemosus in a granola bar had shorter times to breast fullness postpartum and greater volumes of milk at 72 hours than those who received the granola bar formulated without A. racemosus.
Coleus amboinicus
Coleus amboinicus (also called Plectranthus amboinicus) leaves are a traditional galactogogue used in Indonesia called torbangun or bangun-bangun in local languages. No data exist on the excretion of any components of C. amboinicus into breast milk or what ingredients might be active. The safety and efficacy of C. amboinicus in nursing mothers or infants have not been established, although it has been used for hundreds of years in Indonesia with apparent safety.
Only two small, very flawed, unblinded galactogogue studies have been located. They had varied results, with one showing an increase in milk supply and another showing no increase in milk supply compared with other interventions. No conclusion can be made on the effectiveness of Coleus as a galactogogue.
Galega officinalis
Galega officinalis (goat’s rue; French lilac) leaves and flowering tops contain numerous guanidine derivatives, including galegine, which may cause hypoglycemia. In fact, metformin was developed from galegine, and the two compounds have similar chemical structures. Hypothetically, effects on lactation may be mediated through modulating energy production and sensitizing mammary epithelial cells to insulin. This mechanism implies that it might be helpful for women with type 2 diabetes or polycystic ovary syndrome, but studies are lacking. Goat’s rue is usually well tolerated, but it might cause hypoglycemia, so caution should be used in women taking antidiabetic drugs. Diarrhea and hepatomegaly occurred in a woman taking fennel, fenugreek, and goat’s rue as galactogogues.
Goat’s rue is widely used as a galactogogue, and although it has a long history of use, very limited scientific data exist on the efficacy of goat’s rue in nursing mothers or infants. Most studies used combinations in which goat’s rue was only one component in a mixture, and the study quality was very poor. Two studies using a commercial goat’s rue extract from Austria in unspecified doses found increases in milk supply but had extremely flawed designs. Overall, the galactogogue effect of goat’s rue remains to be proven.
Moringa oleifera
Moringa (Moringa oleifera, Moringa pterygosperma) leaves are widely used as food and medicine in Asia and Africa. They contain vitamins, minerals, and essential amino acids, as well as several glycosides. Moringa has been used as a galactogogue in Asia, particularly in the Philippines, where it is called malunggay. Many galactogogue studies have been published, but most are either very small, of poor quality, or both.
Two meta-analyses by the same group analyzed the outcomes of six studies of M. oleifera as a galactogogue. Two studies with a total of 73 patients found that patients in the Moringa groups had a statistically significant average increase in maternal serum prolactin and also found that infant weight gain at week 4 was 11.9% greater in the Moringa group. Pooling of two studies with a total of 51 patients revealed a significant mean increase in milk volume of 124 mL on day 7 in the Moringa groups. One of the studies compared the effects of domperidone and metoclopramide with Moringa. On days 7 and 14, milk volume in all the treatment groups was greater than in the placebo group. The highest volume was in the domperidone group, followed by metoclopramide, and then Moringa. No correlation was found between serum prolactin and milk volume.
One small, relatively well-performed study has been reported since the meta-analyses. A randomized, double-blind, placebo-controlled trial compared capsules containing 450 mg of M. oleifera leaf powder or an identical placebo twice a day before a meal in mothers with full-term, uncomplicated deliveries. At 3 days postpartum, there was a 47% higher volume of milk in the Moringa group, but the difference was not statistically significant. At 6 months postpartum, 52% of women in the Moringa group were exclusively breastfeeding. The placebo group had a 46% exclusive breastfeeding rate at 6 months, which was also not statistically different from the Moringa group. The lack of statistically significant differences in outcomes in this study is possibly because of the small number of subjects and consequent lack of power.
A small, randomized study in Kenyan mothers compared maternal supplementation with 20 g of Moringa leaf powder daily to placebo. At the end of the 3-month study, the mean infant insulin-like growth factor-1 and hemoglobin concentrations were significantly higher in the Moringa group, but no differences in infant growth, serum iron, or vitamin A status were found. Note the difference in dosages used in these last two studies.
Sauropus androgynus
Sauropus androgynus (Breynia androgyna; star gooseberry) is used as a food and medicinal plant in South and Southeast Asia. The leaves are used as a galactogogue in Indonesia and Malaysia, where is to called katuk. It is high in provitamin A carotenoids, vitamins C and E, and several minerals. It also contains papaverine, polyphenols, and flavonoids, especially quercetin and kaempferol. Studies in lactating mice indicate that S. androgynus increased the expression of prolactin and oxytocin genes.
No components of S. androgynus have been measured in milk after its ingestion, but some of its components have been measured after the ingestion of other foods. Both quercetin and kaempferol are normally found in breast milk in varying amounts, originating from plants in the diet. One study measured quercetin levels in milk after giving mothers measured amounts of quercetin in onion soup. Concentrations of quercetin and its conjugates in milk increased by about 50% over baseline, with peak concentrations at about 12 hours after ingestion. Milk quercetin concentrations fell with an average half-life of about 50 hours.
Excessive ingestion of fresh S. androgynus leaves can cause bronchiolitis obliterans, which is potentially fatal. Most poisoning victims have been young and middle-aged women. Cooked leaves may not result in similar toxicity. In one study, 3–5% of women who received Sauropus had elevations of liver enzymes.
Several small studies have attempted to demonstrate the galactogogue effect of Sauropus in humans, but all have design flaws. One study found an increase in milk supply based on infant weighing before and after nursing at 18–19 days of age. Two with no placebos or blinding found a greater increase in infant weight or milk production at 30 days of age among infants whose mothers were given a Sauropus supplement compared with those who were not. The amount of Sauropus given to mothers in these studies varied from 900 mg to 25 g a day, so a reasonable dosage is hard to discern.
One study measured serum prolactin in mothers, and another measured the milk fat or protein content of milk. Neither study found significant differences between mothers who received Sauropus and those who did not.
Summary
Herbal galactogogues are widely used around the world. Some that have their origins in Asia are available in the United States in pharmacies, health food stores, and on the internet. The products available outside their countries of origin can be quite different from those in their native areas. Of the products reviewed in this column, only A. racemosus and M. oleifera have some fair evidence for efficacy as a galactogogue, although the studies do not reach the level of evidence required for FDA approval. The others, C. amboinicus, G. officinalis, and S. androgynus, have little to no good evidence to support their use as galactogogues. On the positive side, most of these products do not appear to be particularly toxic, except for Sauropus and possibly Galega. Breastfeeding clinicians are right to be skeptical of claims of galactogogue activity of herbal products.
Footnotes
Disclosure Statement
No competing financial interests exist.
Funding Information
No funding support was provided for this work.