The effects of dietary flaxseed on the Fischer 344 rat: I. Development, behaviour, toxicity and the activity of liver γ‐glutamyltranspeptidase

Abstract

The effect of exposure to, followed by consumption of, 10% flax chow from the 18th day of gestation to the 86th day after birth was examined in male and female Fischer 344 rats. Growth curves of the flax chow-fed rats were identical to those of regular chow-fed rats, as were such developmental milestones as pinna development, growth of hair and eye opening. Acoustical startle and the righting reflexes, developmental behavioural indices, were also the same. Blood glucose levels were comparable in flax chow-fed and regular chow-fed rats at all stages of development, indicating that flax is without effect on glucose balance. There were no signs of toxicity in the flax chow-fed rats since their plasma levels of alanine aminotransferase and gamma-glutamyltranspeptidase (gammaGT) were the same as those of regular chow-fed rats. The activity of gammaGT displayed an increase in the livers of flax chow-fed rats after puberty, more so in the male-four-fold-than in the female-1.38-fold. This is suggestive of an estrogenic effect which implicates an effect of an estrogenic flax lignan. An hepatobeneficial effect of the flax-induced increase in liver gammaGT is discussed. In summary, dietary 10% flax chow is without long-term effect on growth, development and behaviour, is non-toxic and may be hepatoprotective.

ESCO report: Advice on the EFSA guidance document for the safety assessment of botanicals and botanical preparations intended for use as food supplements, based on real case studies

“…The observed increase in liver GT was considered as a hepatobeneficial effect induced by the flax. The results of the study indicated the absence of developmental toxicity and a possible hepatoprotective effect of flaxseed (Hemmings et al, 2004).…”

“…Dietary 10 % flax chow was without long-term effect on growth, development and behaviour in male and female Fischer 344 rats (Hemmings et al, 2004). In other rat experiments flaxseed affected the reproductive development of offspring, could potentially alter reproduction depending on the dose and timing of exposure, and lifetime or gestation and lactation, and exposure to 5 or 10 % flaxseed in the diet induced structural changes in the mammary gland (Tou et al, 1998(Tou et al, , 1999a(Tou et al, , 1999b.…”

The effects of dietary flaxseed on the Fischer 344 rat: II. liver γ‐glutamyltranspeptidase activity

“…Our recent study indicated that long-term flax feeding has no effect on the growth or behavioural development of the rat, and is without toxic effects. 8 In this study, we also reported that flax consumption effected an increase in the activity of the enzyme -glutamyltranspeptidase (GT) in the liver and that the increase was more pronounced in the male rat than in the female rat. Since this was suggestive of an estrogenic effect, we proposed that the flaxinduced increase in -glutamyltranspeptidase may be due to the estrogenic lignan SDG.…”

“…-GT activity was determined in liver and kidney fractions following our method using L-glutamyl-pnitroanilide as donor and glycylglycine as acceptor. 8 Assays were carried out at 37 C and, in some cases, 50 C to examine the degree of heat activation of the enzyme. Results are expressed as nanomoles p-nitroaniline generated per milligram protein per minute (nmoles Á mg À1 Á min À1 ).…”

“…4,5 The SDG in flax is metabolically converted in mammals to enterolactone and enterodiol which are weakly estrogenic. 6 Scientific studies substantiating flaxseed claims are still relatively few 7,8 but do suggest beneficial effects in animal models of colon cancer, mammary cancer, diabetes mellitus and some forms of heart disease. Significantly, the beneficial component of the flaxseed appears to be the lignan SDG.…”