Chapter II

Review of Related Literature

Since early civilization, various fruits have been traditionally used as folk medicine.

Besides the fruit, bark, leaves, stem, root, twig, and sap have been used as ingredients for

traditional medicine. Plants are very important sources of drugs used for centuries in the

treatment of various microbial infections. Most of the plant-based drugs when used

correctly, pose less or no toxic effect to the recipients compared to the chemically synthetic

drugs. This necessitates the use of natural plants in the complementary medicine in order

to showcase the long term adverse effects of some synthetic drugs.

Herbal drugs have increasingly been used worldwide during the last few decades as

evidenced by rapidly growing global and national markets of herbal drugs. According to

World Health Organization estimates, the demand for medicinal plants is about US $14

billion a year and by the year 2050 it would be about a trillion US dollars. Now people rely

more on herbal drugs because of high price and harmful side effects of synthetic drugs, and

this trend is growing not only in developing countries but in developed countries too (Tor-

anyiin TA, Shaato R., 2003). A number of plants have been indicated to possess

antimicrobial properties from traditional uses (National Committee for Clinical Laboratory

Standard, 1995).

Medicinal plants have therefore been described as one in which one or more of its organs

contain substance that can be used for therapeutic purposes (Rios JL, Recio MC., 2005). It
has been estimated that about one in four of all prescribed drugs, and almost 7,000 different

medicaments contain compounds of plants origin or their derivatives with their commercial

value being put at about $40 billion annually (Carter AP, Cleons WM, Brodersen DE,

Morgan-Warren RI, Wimberly BT, Ramarkrsohan V., 2000).

Studies indicated that about 33% of drugs produced in the developed countries are derived

from plants. Cymbopogon citratus of the poaceae family is a tall, monocotyledonous

aromatic perennial plant with slender sharp-edge green leaves, pointed apex that is native

to tropical Asia. C. citratus is known as Guatemala in West Indian, or Madagascar Lemon

grass. Cymbopogon citratus is cultivated in Africa, the West Indies, Central and South

America, and Tropical regions. Lemongrass, Cymbopogon citratus is one of the important

leaves among the species of grasses, and has various applications in traditional medicine.

The grass is used in food or as culinary used i.e. it is eatable and also it can be used as

cosmetic cream and even as herb. The linear leaves can grow up to 90 cm in height and 5m

in width (Ernst E., 2008).

Cymbopogon citratus

Cymbopogon is a genus of about 55 species, which are indigenous in tropical and semi-

tropical areas of Asia and are cultivated in South and Central America, Africa and other

tropical countries. These are tufted perennial C4 grasses with numerous stiff stems arising
from a short, rhizomatous rootstock, (Weiss EA., 1997) as with citrus flavor, and can be

dried and powdered or used fresh. The name Cymbopogon is derived from the Greek

words “kymbe” (boat) and “pogon” (beard), referring to the flower spike arrangement

(Plants data base. Cymbopogon citrates, inc. c2003). Cymbopogon citratus, Stapf (Lemon

grass) is commonly used in teas, soups and curries. It is also suitable for poultry, fish and

seafood.

The chemical composition of the essential oil of Cymbopogon citratus varies according to

the geographical origin, the compounds as hydrocarbon terpenes, alcohols, ketones, esters

and mainly aldehydes have constantly been registered (Trease GE., W.B Saunders;

1996). The essential oil (0.2–0.5%, West Indian lemon grass oil) consists of, mainly,

citral (Ming L. et al., 1996). Citral is a mixture of two stereoisomeric monterpene

aldehydes; the trans isomer geranial (40–62%) dominates over the cis isomer neral (25–

38%) (Sarer E, Scheffer JJ, Baerheim SA., 1983; Rauber S. et al., 2005).

Antibacterial Activity

The chromatographic fraction of the essential oil in agar plate was active on Bacillus

subtilis, Escherichia coli, Staphylococus aureus (Onawunmia GO et al., 1984; Melo SF et

al., 2001) and Salmonella paratyphi and Shigella flexneri (Syed M. et al., 1990). These

activities are shown in two of the three main components of the oil identified through

chromatographic and mass spectrometric methods. While the α-citral (geranial) and β-

citral (neral) components individually elicit an antibacterial action on gram-negative and

gram-positive organisms, the third component, myrcene, did not show any observable
antibacterial activity on its own (Onawunmia GO et al., 1984). The extract was also

active when the volatile oil extract was oxidized via the active oxygen method (Syed M.

et al., 1990).

Anti-inflammatory Activity

The hot water extract of the dried leaves administered intragastrically to rats was active

when compared with carrageenin-induced pedal edema (Carbajal D. et al., 1989).

Free Radical Scavengers and Antioxidant Effects

Methanol, MeOH/water extracts, infusion and decoction of Cymbopogon citratus were

shown to have free radical scavenging effects by measuring the bleaching of the 1, 1-

diphenyl-2-picryl-hydrazyl (DPPH) radical, scavenging of the superoxide anion and

inhibition of the enzyme xanthine oxidase and lipid peroxidation in human erythrocytes

(Cheel J. et al., 2005).

Dermatotoxicity

Recent animal studies have shown that citral, a major component of the C. citratus oil,

can induce skin irritation. Similar skin reactions have been reported in humans. In a study

by Motoyoshi et al., fifty male volunteers were dermally exposed to 32% citral mixed

with acetone for 48 hours. Positive skin reactions, including the presence of erythema,

edema, papules, and bullous reaction, were observed. Lemon-scented detergent was also
implicated in an outbreak of eczema (Rothenberg HW. et al., 1997; Heydorn S. et al.,

2003)

Are C. Citratus Leaf Extracts Really Toxic?

A number of studies have attempted to answer this question, with conflicting and

inconclusive data. Some studies observed toxic effects, while no toxicity was detected by

others. However, most of these studies were performed in animals, making the results

difficult to apply to humans. Species differences, methods of C. citratus processing,

duration of intake, site of cultivation and the heavy metal content of the soil, as well as

the health status of the individual are only some of the factors that could influence the

toxicity of an herbal preparation. Other micro environmental, physical, and chemical

stimuli known to elicit toxicity could qualitatively and quantitatively alter the

phytochemistry of herbs. Additionally, toxicity of herbal preparations could be due to the

adulteration, contamination from toxins during cultivation and extraction, or even from

herb interactions with any pharmaceutical agents that the subject may be concurrently

taking. However, C. citratus has been used over many years to make caffeine-free tea

and as an herbal drink, suggesting that it may be a healthier alternative to caffeine-

containing tea products (Blanco MM. et al., 2009). Akande et al., found that, in

comparison to other tea brands consumed among Nigerians (Lipton tea, Nescafe, green

tea, and Top tea); C. citratus tea was a good source of antioxidants such as flavonoids,

and therefore a nutritionally acceptable and medicinally valuable beverage. Although

some studies have shown that it contains tannins, coumarins, saponins, and

anthraquinones, which have been associated with minor toxic effects, the low
bioavailability of these phytochemicals in humans may confer a measure of protection

against toxicity. The average concentrations of anti-nutrients such as phytate are not

significantly higher in C. citratus, while cardiac glycosides, cyanates, phlobatannins, and

heavy metals like lead and mercury are absent. Therefore, C. citratus is considered to be

safe for human consumption on the basis of its phytochemical constitution, both

nutritional and nonnutritional. As with other herbs, while C. citratus is relatively safe for

consumption, caution should be taken in high doses and prolonged intake in both healthy

individuals and in diseased states. Additionally, the site of cultivation and methods of

extraction can be a concern, as contamination from environmental or industrial sources

could render the herb toxic. Empirically, since past research has shown that C. citratus

can influence the activities of cytochrome P450 due to its citral contents (Dilberto JJ. et

al., 1988; Srinivas P. et al., 1990), it could interact with drugs that depend on this enzyme

system for their metabolism. However, these interactions need to be confirmed through

further studies. As a general shortcoming in herbal medicine, dosage of administration

cannot be as closely regulated as with conventional drugs. However, Salome et al.

(Salome AC. et al., 2012) have produced C. citratus tablets containing powdered dry C.

citratus leaves by using acacia and gelatin as binders at concentrations of 2, 4, and 8%

w/w. Use of such standardized tablets could help with the monitoring of dose

consistency, quality standardization, and control of dosing. However, further studies are

still warranted to evaluate the bioavailability, as compared to teas and decoctions,

Though consumed for a wide range of diseases, herbal remedies, including C. citratus,

should be used with caution in individuals with kidney damage, liver diseases, in

pregnant or lactating women, or children under the age of six. High dose and prolonged
use of C. citratus tea or decoction should be discouraged of this form, as compared to teas

and decoctions, though consumed for a wide range of diseases, herbal remedies,

including C. citratus, should be used with caution in individuals with kidney damage,

liver diseases, in pregnant or lactating women, or children under the age of six. High dose

and prolonged use of C. citratus tea or decoction should be discouraged.

Solanum lycopersicum

The cultivated tomato, Solanum lycopersicum L., belongs to the diverse family

Solanaceae, which includes more than 3000 species, occupying a wide variety of habitats

(Knapp 2002). The Solanaceae contain many species of economic use such as food

(tomatoes, potatoes, peppers and eggplants), medicines (deadly nightshade, henbane,

datura) and ornamental purposes (petunias). Solanum lycopersicum was previously

recognized as Lycopersiconesculentum Mill.but data from both morphology and

molecular sequences support its inclusion in the large genus Solanum L., and a revised

new nomenclature has resulted (Peralta and Spooner 2001, 2005; Spooner et al. 2005;

Peralta et al. 2006, 2008a).

Health Benefits

Tomatoes, which are actually a fruit and not a vegetable, are loaded with all kinds of

health benefits for the body. They are in fact, a highly versatile health product and due to

their equally versatile preparation options, there's really no reason to neglect the tomato

as part of a healthy diet. (Periago MJ. et al., 2008). The health benefits of tomatoes

are becoming more and more documented every day as we learn new uses of this
amazing fruit. Cancers such as prostate cancer, cervical cancer, colon cancer, rectal

cancer, and cancers of the stomach, mouth, pharynx, and esophagus have all been proven

to be staved off by high levels of Lycopene ((Peralta and Spooner 2001, 2005; Spooner et

al. 2005; Peralta et al. 2006, 2008a). Researchers introduced Lycopene into pre-existing

cancer cell cultures and the Lycopene prevented the continued growth of these cultures.

This is pretty powerful evidence that the health benefits of eating a tomato are really

quite phenomenal. It takes as little as 540 milliliters of liquid tomato product to get the

full benefits of Lycopene. This means that a daily glass of tomato juice has the potential

to keep a person healthy for life. Tomatoes are equally as nutritious fresh as they are in

other variable forms (Peralta and Spooner 2001, 2005; Spooner et al. 2005; Peralta et al.

2006, 2008a). When tomato products are heat processed the bioavailability of the

Lycopene actually increases rather than the anticipated decrease. Even with all the

plentiful research that has gone into the health benefits of tomatoes, there is still more

research being conducted as the medical science community understands that we have not

fully tapped into the potential presented by a tomato just yet (Peralta and Spooner 2001).

Research is now slowly proving that there is a high likelihood that the consumption of

tomatoes and tomato based products actually may prevent serum lipid oxidation and

reduce the risk of macular degenerative disease. Tomatoes are by far the healthiest of the

fruits and vegetables with the power to ward off some of the worst known diseases to

man (Peralta and Spooner 2001)

Home Remedy of Solanum lycopersicum

Tomatoes contain all four major carotenoids: alpha- and beta-carotene, lutein, and

lycopene. These carotenoids may have individual benefits, but also have synergy as a

group (that is, they interact to provide health benefits) (Jacob K. et al. 2006). In

particular, tomatoes contain awesome amounts of lycopene, thought to have the highest

antioxidant activity of all the carotenoids (-). Tomatoes contain all three high-powered

antioxidants: beta-carotene (which has vitamin A activity in the body), vitamin E, and

vitamin C. A U.S. Department of Agriculture report, What We Eat in America, noted that

a third or we get too little vitamin C and almost half get too little vitamin A. 6 (-).

Tomatoes are rich in potassium, a mineral most of us don't get enough of. A cup of

tomato juice contains 534 milligrams of potassium, and 1/2 cup of tomato sauce has 454

milligrams (-).

Medicinal Uses of Solanum lycopersicum

Tomatoes are good for your skin. Tomatoes contain a high level of lycopene, which is a

substance that is used in some of the pricier facial cleansers that are available for

purchase over-the-counter. If you want to try tomatoes for skin care, you need to start

with about eight to twelve tomatoes. Peel the tomatoes and then place the skin on your

face with inside of the tomato touching your skin. Leave the tomatoes on your face for a

minimum of ten minutes, then wash. Your face will feel clean and shiny. Some redness

may occur, but should fade with time (-). Tomatoes provide essential antioxidants.
Tomatoes contain a great deal of Vitamin A and Vitamin C. This is primarily because

these vitamins and beta-carotene work as antioxidants to neutralize harmful free radicals

in the blood. Free radicals in the blood stream are dangerous because it may lead to cell

damage. Remember, the redder the tomato you eat is, the more beta-carotene it contains.

In addition, you also want to keep in mind that cooking destroys the Vitamin C, so for

these benefits, the tomatoes need to be eaten raw (-). Thermally Treated Tomatoes are

more efficient Unlike fruits and vegetables which reduce their nutritional content when

are thermally treated, such as vitamin C, thermally treated tomatoes increase the

concentration of lycopene and the antioxidant properties are not lost. Moreover, studies

have confirmed that the body absorbs better the lycopene from tomatoes when they are

thermally treated (-). Antioxidants are substances (vitamins, minerals, natural coloring)

that protect body cells from the harmful effects of free radicals, molecules that form in

the body through contact with oxygen. Free radicals are partly responsible for the

processes of aging, cardiovascular diseases and cancer and act by attacking the cell

membranes and the cellular DNA (-).

Health Properties of Solanum lycopersicum

Tomatoes contain all four major carotenoids: alpha- and beta-carotene, lutein, and

lycopene. These carotenoids may have individual benefits, but also have synergy as a

group (that is, they interact to provide health benefits) (-).

Tomato is the most popular vegetable in the world because of its taste, colour and high

nutritive value and also for its diversified use. There are many factors involved in low

yield of tomato; among them are infestations by fungi, bacteria, nematodes or viruses and

the competing weeds are predominant. The most urgent need is to develop biocontrol

agents and varieties of tomato that can resist the ravage of important fungal diseases like

early blight, late blight and wilt because, crop rotation, breeding for resistant plant

varieties and application of pesticides are insufficient to control. Hence earlier research

reports relevant to present attempt are collected and presented here.

In the vast and interesting history of crop cultivation, before the dawn of the 20th

century, there is little question that the work of Charles Darwin and Gregor Mendel

created the scientific foundation for plant breeding that led to its explosive impact over

the past 150 years (Aziz, 2009). Lycopersicon esculentum (tomato) is one of the

important "protective foods" both because of its special nutritive value and widespread

production. It is the world's largest vegetable crop after potato and sweet potato, but it

tops the list of canned vegetables (Babu et al., 2004).

The Lycopersicon esculentum (Tomato) has been a good model plant to analyse plant

pathogen interactions and its prospects for the future are promising. Tomato is one of the

most popular vegetables worldwide however; its cultivation has been limited by an

abundant attack of pathogens. In order to establish effective control methods; analysis of

tomato pathogen interactions are important (Tsutomu et al., 2007).

 Previously tomatoes were grown only during favorable season, but now a days tomatoes

are grown round the year. Because of its economic importance area under cultivation is

increasing every year. The estimated area and production of tomato for India are about

3,50,000 hectares and 53,00,000 tons respectively. Worldwide tomato production in 2005

totaled 29.9 million metric tons and production for the 2005/2006 season in Europe

totaled 10.6 million metric tons. Tomato is the second largest vegetable crop in India.

The average productivity of tomato in our country is merely 158q/ha while its

productivity in USA is 588q/ha, in Greece 498q/ha, in Italy 466q/ha and 465q/ha in

Spain. Ten most promising states of India for tomato crop have been identified and

utilized for further study on various aspects of tomato crop. Bihar State is at leading

position followed by UP and Orissa in terms of area under tomato crop. The maximum

production and productivity have been shown by UP followed by Karnataka, Punjab,

West Bengal and Assam. India’s export of value added tomato products was around

758.6 tons, which included 41 tons of canned tomato products, 38 tons tomato juice

valued at and 595 tons ketchup in the year 2005-2006. This accounts for more than

thousand crores to the Indian economy even with least price like three rupees per kilo.

This significant achievement in tomato production is possible due to the development of

high

Role of diet in Acne

Entire books, such as the Dietary Cure for Acne, are devoted to dietary intervention (with

a role for a low glycemic load diet) for the treatment of acne, and some practitioners

recommend these books to their patient (Rigopoulos D, Gregoriou S, Ifandi A, et al.

Coping with acne: beliefs and perceptions in a sample of secondary school Greek pupils.

J Eur Acad Dermatol Venereol. 2007;21:806–810.)

Therefore, it is imperative that dermatologists know what patients think when it comes to

acne. For more than 30 years, most dermatologists have told patients that acne is not

caused by what they eat. These concepts came from two studies evaluating the role of

chocolate, chocolate bars, milk, peanuts, and Coca-ColaTM> in acne (2. Loren Cordain.,

Phd. Fort Collins, CO: Paleo Diet Enterprises; 2006. The Dietary Cure for Acne).

The study involving chocolate is frequently misinterpreted for a few reasons. First, the

difference between the “imitation” chocolate and “real” chocolate bars was cacao solids

(cacao paste and cocoa butter). There was also no difference in sugar and fat content in

the bars and there was no milk in the bars. Regardless, this study has been held as a

standard for many years, although critiques are understandable as nutritional research

advances (Fulton JE, Plewig G, Kligman AM. Effect of chocolate on acne vulgaris.

JAMA. 1969;210:2071–2074).

Of note, most studies on acne and diet are hampered by various confounders including

genetics, ethnicity, and sex of the patient, and some by lack of controlled dietary groups.
 The practitioner reading such studies should be aware of possible biases. A diet with a

high glycemic load may play a role in the pathogenesis of acne. Glycemic load assesses

the potential of a food to increase blood glucose and is defined as glycemic index

multiplied by carbohydrate content. The glycemic index is a relative comparison of the

potential of various foods to increase blood glucose given that there is an equal amount of

carbohydrate in the food (4. Anderson PC. Foods as the cause of acne. Am Fam

Physician. 1971;3:102–103).

Glycemic Load and Acne

Glycemic index is a measure of carbohydrate quality (i.e., nature or source), but not

quantity.7 Glycemic load takes into consideration carbohydrate quality and

quantity.7Furthermore, there is some variability in the values assigned to foods

depending on geographic location (i.e., brown rice from Canada compared to brown rice

from the United States) as well as the particular preparation of the food (i.e., fresh corn

compared to frozen corn) (Cordain L. Implications for the role of diet in acne. Semin

Cutan Med Surg. 2005;24:84–91).

Low glycemic index foods have values between 1 and 55, moderate glycemic index foods

have values between 56 and 69, and high glycemic index foods have values between 70

and 100. Glycemic load values between 1 and 10 are low, glycemic load values between

11 and 19 are moderate, and a glycemic load value of 20 or more is considered high.
Table 1 lists the glycemic indices and loads for a variety of foods, and shows that

processed foods, such as white bread and doughnuts, have much higher glycemic loads

than unprocessed fruits and vegetables. For a complete database on the glycemic indices

and loads for a large number of foods as well as information on the glycemic index,

practitioners can refer their patients. Cordain et al proposed that there may be an

association between acne and glycemic load, reporting the prevalence of acne in two non-

Westernized populations (Jenkins DJ, Wolever TM, Taylor RH, et al. Glycemic index of

foods a physiological basis for carbohydrate exchange. Am J Clin Nutr. 1981;34(3):362–

366).

These populations, the Ache hunter-gatherers of Paraguay and the Kitavan Islanders of

Papua New Guinea, had no evidence of acne. The authors hypothesized that these people

had low glycemic loads. Their diets differ from Westernized diets, which often create a

high glycemic load. However, controversy with this study stems from debate as to how

much of the condition is related to genetics versus environment. To truly elucidate the

role of diet in acne, there must be a mechanism by which diet leads to the development of

acne (Foster-Powell K, Holt SH, Brand-Miller JC. International table of glycemic index

and glycemic load values: 2002. Am J Clin Nutr. 2002;76:5–56).

The patients' skin surface lipids were analyzed after tape stripping collection with the

results suggesting a change in fatty acid composition of sebum. When evaluating the

study, it must first be noted that sebum is not the sole cause of acne; acne is a
multifactorial disease. Secondly, the change in sebum composition could have been

related to the weight loss the experimental subjects experienced. Finally, the study

included only males, and it did not take into account genetics (Cordain L, Lindeberg S,

Hurtado M, et al. Acne vulgaris: a disease of Western civilization. Arch Dermatol.

2002;138(12):1584–1590).

IGF-1 is a hormone that has a structure similar to insulin and is involved in cell growth

and proliferation. IGF-1 promotes acne by inducing hyperkeratosis and epidermal

hyperplasia, a first step in the follicular plug (Smith RN, Braue A, Varigos GA, Mann NJ.

The effect of a low glycemic load diet on acne vulgaris and the fatty acid composition of

skin surface triglycerides. J Dermatol Sci. 2008;50:41–52).

IGF-1 also stimulates sebaceous gland lipogenesis and androgens which are known to

cause an increase in sebum. (10. Holt SH, Miller JC, Petocz P. An insulin index of foods

the insulin demand generated by 1000-kJ portions of common foods. Am J Clin Nutr.

1997;66:1264–1276).

It appears that IGF-1 and androgens can act synergistically in the pathogenesis of acne.

This carries over to the clinic setting, where post-adolescent women (20–25 years) with

acne had higher levels of IGF-1 versus those women without acne (Edmondson SR,

Thumiger SP, Werther GA, et al. Epidermal homeostasis the role of the growth hormone

and insulin-like growth factor systems. Endocr Rev. 2003;24:737–76)

Young men with acne have also been studied with respect to their diet. Smith et al

recently studied 43 men (15–25 years) with acne who were given instructions to follow a

high carbohydrate diet similar to their current diet (control group) compared to a group

given instructions to follow a low glycemic load diet for 12 weeks ( Deplewski D,

Rosenfield RL. Growth hormone and insulin-like growth factor have different effects on

sebaceous cell growth and differentiation. Endocrinology. 1999;140:4089–4094).

There was a significant decrease in the number of acne lesions following diet

modification in the low glycemic load group compared to the control group.15 The low

glycemic load group also noted weight loss, reduced free androgen index and

dehydroepiandrosterone sulfate (DHEAS), and increased insulin-like growth factor

binding protein-1 (IGFBP-1), which is known to be inversely correlated with insulin and

free IGF-1 levels (Smith RN, Mann NJ, Braue A, et al. The effect of a high-protein, low

glycemic-load diet versus a conventional, high glycemic-load diet on biochemical

parameters associated with acne vulgaris: a randomized, investigator-masked, controlled

trial. J Am Acad Dermatol. 2007;57(2):247–256).

Another prospective cohort study of 49 university students (men and women) were also

evaluated with respect to their diets, presence of acne, and specific laboratory values. In

this study, no differences were observed between patients with acne and controls in

serum glucose, insulin, leptin, overall glycemic index, or glycemic load (16. Smith RN,
Mann N, Roper J, et al. A pilot study to determine the short-term effects of a low

glycemic load diet on hormonal markers of acne: a nonrandomized, parallel, controlled

feeding trial. Mol Nutr Food Res. 2008;52(6):718–726).

The one result that can be viewed with interest was that the glycemic index was

significantly higher in patients with acne for longer than two years compared to those

with acne for less than two years.17 This may be relevant to the recent increase in

prevalence of adult acne noted by many physicians, and should be further explored.

Limitations to this study include small sample size and patient recall bias (Kamayak Y,

Adisen E, Ilter N, et al. Dietary glycemic index and glucose, insulin, insulin-like growth

factor-I, insulin-like growth factor binding protein 3, and leptin levels in patients with

acne. J Am Acad Dermatol. 2007;57(5):819–823).

In clinical practice how can we connect IGF-1 and acne? Some of our best evidence for a

role of diet comes from patients with polycystic ovarian disease (PCOS). PCOS is

characterized by acne, irregular menses, alopecia, hirsutism, infertility, insulin resistance,

and obesity. However, a patient can have PCOS and not have all of its characteristics.

Laboratory evaluations of such patients reveal increased levels of insulin, free IGF-1, and

androgens and decreased IGFBP-1 levels (Thierry van Dessel HJ, Lee PD, Faessen G, et

al. Elevated serum levels of free insulin-like growth factor I in polycystic ovary

syndrome. J Clin Endocrinol Metab. 1999;84(9):3030–3035).

Interestingly, acne improves with medications that improve insulin metabolism, such as

metformin, tolbutamide, and pioglitazone, indicating the insulin metabolism plays a role

in the pathogenesis of acne in PCOS patients.21Insulin-sensitizing agents also increase

IGFBP-1 levels and decrease IGF-1 levels (Homburg R, Pariente C, Lunenfeld B, Jacobs

HS. The role of insulin-like growth factor-1 (IGF-1) and IGF binding protein-1 (IGFBP-

1) in the pathogenesis of polycystic ovary syndrome. Hum Reprod. 1990;5(1):32–35).

Unfortunately, there has been no study of the effects of a low glycemic diet on acne and

IGF-1 levels in PCOS patients. Further investigation of the relationship between diet,

acne, and IGF-1 levels is necessary, particularly in PCOS patients. Milk consumption has

also been associated with increased IGF-1 levels and implicated in the pathogenesis of

acne (Suikkari A, Ruutiainenen K, Erkkola R, Seppala M. Low levels of low molecular

weight insulin-like growth factor-binding protein in patients with polycystic ovarian

disease. Hum Reprod. 1989;4(2):136–139).

In addition to IGF-1, it is important to note that milk contains a variety of other hormones

including estrogens; progesterone, which can act as an androgen receptor agonist; and

dihydrotestosterone (DHT) precursors such as 5-pregnanedione and 5-androstenedione

(De Leo V, Musacchio MC, Morgante G, et al. Metformin treatment is effective in obese

teenage girls with PCOS. Hum Reprod. 2006;21(9):2252–2256).

While progesterone and DHT precursors may be important in promoting acne in milk

consumers, estrogen, in the form of birth control, has been used to treat acne. Therefore,

it is unclear whether hormones in milk promote acne or protect against it. The association

between milk consumption and acne has been known for many years and has gained

more support from recent studies (Pawelczyk L, Spaczynski RZ, Banaszewska B, Duleba

AJ. Metformin therapy increases insulin-like growth factor binding protein-1 in

hyperinsulinemic women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod

Biol. 2004;113(2):209–213).

One study of 47,355 women from the Nurses Health Study II retrospectively assessed

dietary intake and whether participants had acne during their teenage years. The

participants completed questionnaires regarding diet and teenage acne. This study found a

positive association between milk and teenage acne (Berker B, Emral R, Demirel C, et al.

Increased insulin-like growth factor-1 levels in women with polycystic ovary syndrome,

and beneficial effects of metformin therapy. Gynecol Endocrinol. 2004;19(3):125–133).