TOPIC: Milk, Galactose and Fertility

A new suspect in infertility may be as close as your refrigerator. Dairy products contain lactose, which must be broken down into two simple sugars--glucose and galactose--during digestion. If you have a problem with lactose, you may also have a problem with galactose irritating your ovaries possibly due to the dependency of bacteria breaking it down lower inside the large intestines-colon

Galactose, Cows Milk and Fertility

It appears that galactose may not be friendly to ovaries. Daniel Cramer, MD, at Harvard Medical School has conducted ongoing research studying the effects of dairy consumption and associated damage to the ovaries, specifically in the area of ovarian cancer. Looking at Cramer's research, and that of others, Neal Barnard, MD, has concluded that because galactose has been associated with increased risk of ovarian cancer we can assume its toxicity may also interfer with fertility.

Compounding the problem, some women have low levels of the enzyme needed to break apart this sugar and galactose builds up dangerously. Reduce your consumption of "milk, ice cream, and cottage cheese, which are loaded with galactose," says Barnard. "There is plenty of highly absorbable calcium in green leafy vegetables, beans, enriched flour, and fortified juices."

From Better Nutrition 11/2000

Research on the mechanisms of premature ovarian failure.

Santoro, N www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%2011223362
J Soc Gynecol Investig. 2001 Jan-Feb;8(1 Suppl Proceedings):S10-2.
Division of Reproductive Endocrinology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. This email address is being protected from spambots. You need JavaScript enabled to view it.

As many as 5% of women may experience menopause at or before age 45 (POF). Four causes are known for POF: (1) Genetic. Clear-cut X chromosome deletions, particularly those in the critical region, result in truncation of reproductive lifespan. Creation of a central genetic data bank for women with POF may assist in defining the genetic contribution to this condition. (2) Autoimmune. POF coexists with virtually all of the permutations of the autoimmune polyglandular failure syndromes, most often in linkage with antithyroid and antiadrenal antibodies. (3) Iatrogenic. Iatrogenic POF results from repeated ovarian surgeries, or from the underlying disease that led to the surgery. (4) Environmental. Environmental toxicants are difficult to pinpoint, but evidence suggests that galactose consumption is linked to early menopause.

 We investigated the possibility that POF represented premature endocrine aging that was generalized, rather than specifically targeted to the ovary. Detailed investigation of the gonadotropin-releasing hormone-luteinizing hormone system, the somatotrophic axis, the adrenal glucocorticoid and androgen axes, and the prolactin axis have led us to conclude that women with POF are not prematurely aged in any endocrine system other than the ovary. Basic research on how the ovary interacts with the immune system, particularly in the early stages of oogenesis, how the oocyte and follicle interact in fetal life, and how follicles might be protected from damage in the case of immune self-attack are all fruitful avenues of clinically applicable work that may lead to treatments for this most vexing reproductive disorder.

PMID: 11223362 [PubMed - indexed for MEDLINE]

 

1: Reprod Toxicol. 2000 Sep-Oct;14(5):377-84
www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%2011020650

Galactose metabolism and ovarian toxicity.
Liu G , Hale GE , Hughes CL .
Center for Women's Health, Cedars-Sinai Burns and Allen Research Institute, Cedars-Sinai Medical Center/University of California Los Angeles, School of Medicine, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.

Galactose is an energy-providing nutrient and also a necessary basic substrate for the biosynthesis of many macromolecules in the body. Metabolic pathways for galactose are important not only for the provision of these pathways but also for the prevention of galactose and galactose metabolite accumulation. Problems with galactose metabolism can cause a variety of clinical manifestations in animals and humans. It has been found that the mammalian ovary is particularly susceptible to damage from the accumulation of galactose and galactose metabolites. The galactose metabolites Gal-1-P, galactitol, and UDPgal are all considered to be important in this toxicity and proposed mechanisms include interference with ovarian apoptosis and gonadotrophin signaling. This review addresses the most recent scientific findings regarding the possible mechanisms of galactose-induced ovarian toxicity and also the possible protective role of hormonal and antioxidant therapy. In addition, the available epidemiologic and scientific evidence linking galactose intake with risk of ovarian cancer is discussed.

PMID: 11020650 [PubMed - indexed for MEDLINE]

:Cancer. 1994 Aug 15;74(4):1309-17.
www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%208055453
Characteristics of women with a family history of ovarian cancer. I. Galactose consumption and metabolism.

Cramer DW , Muto MG , Reichardt JK , Xu H , Welch WR , Valles B , Ng WG .
Familial Ovarian Cancer Clinic, Obstetrics and Gynecology Epidemiology Center, Boston, Massachusetts.

BACKGROUND. Galactose metabolism may be a risk factor for ovarian cancer based upon evidence that galactose causes ovarian failure and that ovarian cancer arises from premature ovarian failure. This study examines galactose-1-phosphate uridyl transferase (GALT) activity in women with a family history of ovarian cancer (FOC) to determine if low GALT activity occurs in women who are at risk for but in whom ovarian cancer has not yet developed. METHODS. The authors studied 106 premenopausal women (FOC patients) with one primary or two second-degree relatives with ovarian cancer compared with 116 age matched control subjects without a family history of ovarian cancer (FOC controls). All women completed questionnaires and had blood drawn to measure GALT activity and genotype.

 RESULTS. Mean erythrocyte GALT activity, in micromoles of hexose conversion per hour per gram of hemoglobin was 21.5 in FOC patients, significantly lower than the mean of 23.1 observed in FOC control subjects, (P = 0.001). FOC patients more frequently displayed the Duarte variant of galactosemia as detected by electrophoresis. In a subset of 87 patients and 113 control subjects for whom DNA was available, the allelelic frequency of the Duarte variant based upon molecular genetic detection of the N314D mutation that is associated with the Duarte variant was 15.5% among FOC cases compared with 7.5% among control subjects (P < 0.02). Galactose consumption did not differ between FOC patients and control subjects.

CONCLUSION. Galactose metabolism differs between women with and without a family history of ovarian cancer, suggesting that it may be a genetic risk factor for ovarian cancer, possibly mediated through oocyte toxicity from galactose.

PMID: 8055453 [PubMed - indexed for MEDLINE

Mol Genet Metab. 2010 Oct 20. [Epub ahead of print]

http://www.ncbi.nlm.nih.gov/pubmed/21059483

The GALT rush: High carrier frequency of an unusual deletion mutation of the GALT gene in the Ashkenazi population.
Goldstein N , Cohen Y , Pode-Shakked B , Sigalov E , Vilensky B , Peleg L , Anikster Y .

Metabolic Disease Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel-Hashomer, Israel.


Abstract
Classic galactosemia is an autosomal recessive disorder of galactose metabolism manifesting in the first weeks of life following exposure to a milk-based diet. Despite the benefit of avoidance of lactose, many patients suffer from long-term complications including neurological deficits and ovarian failure.

To date, over 230 mutations have been described in the GALT gene resulting in galactosemia. Recently, an unusual mutation was characterized causing a 5.5kb deletion, with a relatively high carrier rate in subjects of Ashkenazi Jewish (AJ) descent.

 The aim of this study was to estimate the carrier frequency of this mutation in the AJ population in Israel. For this purpose we developed a high-throughput methodology to genotype both normal and deleted alleles using a chip-based matrix-assisted laser desorption-time-of-flight (MALDI-TOF) mass spectrometer and Multiplex PCR. DNA samples of 760 anonymous AJ subjects were submitted for analysis, subsequently detecting six individuals heterozygous for the GALT deletion mutation, giving a carrier frequency of 1 in 127 (0.79%). Based on these results, we suggest that the method described here provides a basis for genetic screening and prenatal counseling and can potentially reduce the morbidity and mortality associated with delayed diagnosis of galactosemia in this patient population.


Copyright © 2010 Elsevier Inc. All rights reserved.
PMID: 21059483 [PubMed - as supplied by publisher]



Obstet Gynecol Surv. 2008 May;63(5):334-43.

Fertility and impact of pregnancies on the mother and child in classic galactosemia.
Gubbels CS , Land JA , Rubio-Gozalbo ME .

Department of Pediatrics, University Hospital Maastricht, The Netherlands.


Abstract
Despite the high prevalence of premature ovarian failure (POF) and subsequent infertility in galactosemic women, spontaneous pregnancies occur and may not be as rare as is generally assumed. This is important for counseling these women on fertility. The purpose of this review is to assess the occurrence and predicting factors of pregnancy, and to evaluate the impact of pregnancy on the mother's and child's health. The female Dutch galactosemia population (age > 18 years) was studied, and a literature search on articles reporting pregnancy in galactosemic women, published between January 1971 and December 2007, was performed.

 Twenty-two galactosemic women were studied. Nine women have tried to conceive, of which 4 were successful. Three mothers were diagnosed with POF before the first pregnancy and/or in between pregnancies. In literature, 50 pregnancy reports were found. In 10 pregnancy reports from the literature, the mother's genotype is known. Four women were homozygous for the Q188R mutation, which equals the incidence of 40-45% of classic galactosemia caused by this mutation.

 This study challenges the current opinion that the chance of becoming pregnant is small in classic galactosemia. Despite POF in most galactosemic women, pregnancies do occur. The genotype and GALT-activity do not seem to predict the chance of becoming pregnant, whereas the occurrence of spontaneous menarche might. No evidence for the need of additional check-ups during the pregnancy and puerperium was found. Elevations in galactose-metabolites do occur, but without evidence of clinical impact for the mother or the child, although possible long-term effects have not been thoroughly investigated.

TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to summarize the purported causes and sequelae of galactosemia, explain the possible sequelae of galactosemia, distinguish alterations of the ovary and the hypothalamic-pituitary axis, identify the frequency of pregnancy and the possible outcome of the offspring, and outline dietary management of patients with galactosemia.

PMID: 18419833 [PubMed - indexed for MEDLINE]

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