PUFA Increases Estrogen

Also see:
PUFA Inhibit Glucuronidation
PUFA, Estrogen, Obesity and Early Onset of Puberty

Quotes by Ray Peat, PhD:
“The pro-estrogenic nature of the unsaturated fatty acids is probably the biggest barrier to the radical elimination of degenerative diseases. Various saturated fatty acids, including butyric, octanoic, and palmitic, have protective effects on mitochondrial respiration.”

“Two ubiquitous carcinogenic factors that can be manipulated without toxins are the polyunsaturated fatty acids (PUFA) and estrogen. These closely interact with each other, and there are many ways in which they can be modulated.”

“The unsaturated fatty acids, but not the saturated fatty acids, free estrogen from the serum proteins that bind it, and increase its availability and activity in tissue cells.”

“While the competition by PUFA for protein binding sites block the effects of thyroid hormone and vitamin A, the actions of PUFA on sex steroid binding protein (SBP, or SSBG, for sex steroid binding globulin) increases the activity of estrogen. That’s because the SSBG neutralizes estrogen by binding to it, keeping it out of cells; free PUFA keep it from binding estrogen (Reed, et al.).”

J Steroid Biochem. 1986 Feb;24(2):657-9.
Free fatty acids: a possible regulator of the available oestradiol fractions in plasma.
Reed MJ, Beranek PA, Cheng RW, James VH.
Consumption of dietary fats has been linked to the high incidence of breast cancer found in Western women. In vitro studies we have carried out show that unsaturated free fatty acids can increase the biologically available oestradiol fractions in plasma. It is possible therefore that the increased risk for breast cancer associated with a diet high in fats may be related to an elevation in the biologically available oestradiol fractions in plasma.

Ann N Y Acad Sci. 1988;538:257-64.
Possible relevance of steroid availability and breast cancer.
Bruning PF, Bonfrer JM.
The as yet circumstantial evidence for a central role of estrogens in the promotion of human breast cancer is supported by many data. However, it has not been possible to identify breast cancer patients or women at risk by abnormally elevated estrogen levels in plasma. The concept of available, i.e., non-SHBG bound sex steroid seems to offer a better understanding than total serum steroid levels do. We demonstrated that sex steroid protein binding is decreased by free fatty acids. This finding may help to explain how the affluent Western diet and sedentary life style is related to high incidence rates of breast cancer. We have postulated that it is especially the central (abdominal) type of obesity which may increase sex steroid availability. This mechanism could be important already at the age of breast development when the sensitivity to promotion seems relatively great. It may also explain the increased incidence rates which are observed in Western industrialized countries after menopause. It seems likely that other endocrine-related cancer, such as endometrial or prostatic carcinomas are influenced in an analogous way.

Prostaglandins Leukot Essent Fatty Acids. 1993 Jan;48(1):111-6.
The role of free fatty acids in regulating the tissue availability and synthesis of sex steroids.
Reed MJ, Dunkley SA, Singh A, Thomas BS, Haines AP, Cruickshank JK.
Sex steroids and dietary fat intake have been implicated in the growth of breast tumours. We have previously shown that the plasma free oestradiol fraction is increased in women with breast cancer and that the addition of free fatty acids (FFA) to plasma can increase the free oestradiol fraction in vitro. In the present study we have examined the distribution of oestradiol and testosterone in serum obtained from European women (EW) and Asian (Gujarati) women (GW) living in north-west London. Fat intake by these women is similar but GW, who are vegetarians, consume a greater proportion of unsaturated fats. In serum from perimenopausal GW, the free testosterone concentration was significantly higher than for EW (11.1 +/- 3.6 pmol/l vs 8.7 +/- 3.4 pmol/l, p < 0.05). Although a significant correlation was found between the free testosterone and FFA concentrations for GW (r = 0.49, p < 0.05), concentrations of sex-hormone binding globulin (SHBG) were significantly lower in GW than EW. The finding of lower SHBG concentration in GW was confirmed in a second study in postmenopausal women (EW, 60.1 +/- 34.1 nmol/l; GW, 37.8 +/- 20.5 nmol/l, p < 0.05). However, no difference in the free oestradiol fraction or concentration was detected for EW and GW and no correlations with total or individual FFA were found. It is concluded from this study that while dietary fats may have an important role in the development of breast tumours, it is unlikely to be mediated by FFA inhibiting the binding of sex steroids to plasma proteins.

Another interesting association of the highly unsaturated fats and estrogen in relation to brain function is that DHA increases the entry of estrogen into the pregnant uterus, but inhibits the entry or progesterone (Benassayag, et al., 1999) which is crucual for brain cell growth. – Ray Peat, PhD

Prostaglandins Leukot Essent Fatty Acids. 1999 May-Jun;60(5-6):393-9.
Does high polyunsaturated free fatty acid level at the feto-maternal interface alter steroid hormone message during pregnancy?
Benassayag C, Rigourd V, Mignot TM, Hassid J, Leroy MJ, Robert B, Civel C, Grangé G, Dallot E, Tanguy J, Nunez EA, Ferré F.
Polyunsaturated fatty acids (PUFA) are important in pregnancy, fetal development and parturition. We measured free fatty acids (FFA), albumin and alpha-fetoprotein (AFP) in the maternal and fetal circulations of women undergoing elective Caesarean section at term. We also studied the impact of PUFAs on estrogen (ER) and progesterone receptors (PR) binding properties in vitro in the myometria of pregnant women and ex vivo in human myometrial cells in culture. FFA in intervillous blood (I) (feto-maternal interface) and maternal peripheral blood (M) were similar, while those in the umbilical vein (V) and arteries (A) were 2-4 fold lower (P<0.001). PUFA levels were low in M and 3 fold higher in I, A and V (P< 0.001); consequently C20:4 and C22:6 were most abundant in intervillous space. Albumin was uniformly distributed throughout the maternal-fetal unit, but there was a transplacental gradient in AFP. The AFP in the intervillous space had a special conformation (less immuno-reactive, more anionic), suggesting loading with PUFA. Physiological concentrations of C20:4 stimulated estradiol binding, but inhibited progestin binding. C20:4 inhibited progesterone binding by decreasing the number of binding sites, with no change in apparent affinity, in vitro in myometrial tissue and ex vivo in myometrial cells. Thus PUFA may modulate the steroid hormone message, so that the high C20:4 concentration at the maternal-fetal interface at term may help amplify the estrogen signal and inhibit the progesterone signal.