Reference: Bakewell L, Burdge GC, Calder PC., Br J Nutr. 2006 Jul;96(1):93-9.

Young women of reproductive age appear to have a greater capacity than men to convert the essential fatty acid alpha-linolenic acid to DHA. The purpose of this study was to test the hypothesis that gender-related differences in n-3 PUFA metabolism are reflected in the concentrations of n-3 PUFA in plasma lipids. The subjects were healthy men (n 13) and women (n 23) aged 18-35 years consuming their habitual diet. Dietary habits were assessed by food-frequency questionnaire. Venous blood samples were collected following an overnight fast. For the women, blood collection took place on the tenth day of their menstrual cycle. The fatty acid concentrations of plasma phosphatidylcholine, triacylglycerol, NEFA and cholesteryl esters were determined by gas chromatography. There were no significant differences between men and women in their consumption of protein, carbohydrate, total fat, alcohol, individual fatty acids and selected micronutrients. DHA concentration alone was significantly higher in plasma phosphatidylcholine (31 %, P = 0.02), triacylglycerol (71 %, P = 0.02) and NEFA (33 %, P = 0.01), but not cholesteryl esters, in women compared with men. There were no significant differences between men and women in the concentrations of any other fatty acids measured. Overall, the present data support the suggestion that greater DHA synthesis in women than men results in a higher DHA concentration in plasma lipids.

Blaak E., Curr Opin Clin Nutr Metab Care. 2001 Nov; 4(6):499-502.

Women generally have a higher percentage of body fat than men. Also, women store more fat in the gluteal-femoral region, whereas men store more fat in the visceral (abdominal) depot. This review focuses on differences in regional fatty acid storage, mobilization and oxidation that may contribute to gender-related differences in body fat distribution. There are pronounced regional differences in the regulation of regional fatty acid metabolism between men and women. Firstly, there is evidence that in vivo, catecholamine mediated leg free fatty acid release is lower in women than in men, whereas free fatty acid release from the upper body depots is comparable. These data correspond to in-vitro adipose tissue biopsy data, which indicate a more pronounced difference in catecholamine mediated lipolysis between upper body and lower body fat depots in women than in men. Secondly, free fatty acid release by the upper body subcutaneous fat depots is higher in men than in women, indicating a higher resistance to the antilipolytic effect of meal ingestion in the upper body fat depots in men. Thirdly, there are indications that basal fat oxidation (adjusted for fat free mass) is lower in females as compared to males, thereby contributing to a higher fat storage in women. Finally, postprandial fat storage may be higher in subcutaneous adipose tissue in women than in men, whereas storage in visceral adipose tissue has been hypothesized to be higher in men. All the above differences may play a role in the variation in net regional fat storage between men and women, but the number of in-vivo studies on gender-related differences in fatty acid metabolism is very limited and most findings require confirmation. Furthermore, there is abundant evidence that the proportion of energy derived from fat during exercise is higher in women than in men. With respect to total body fat, this finding seems counterintuitive, as percentage body fat is increased in women. Further studies are necessary to investigate the significance of differences in exercise-induced fat oxidation on 24-h fat balance.

Burdge G., Curr Opin Clin Nutr Metab Care. 2004 Mar;7(2):137-44.

Overall, alpha-linolenic acid appears to be a limited source of longer-chain n-3 fatty acids in man and so adequate intakes of preformed n-3 polyunsaturated fatty acids, in particular docosahexaenoic acid, may be important for maintaining optimal tissue function. Capacity to upregulate alpha-linolenic acid transformation in women may be important for meeting the demands of the fetus and neonate for docosahexaenoic acid.

Childs CE, Romeu-Nadal M, Burdge GC, Calder PC. Proc Nutr Soc. 2008 Feb;67(1):19-27. doi: 10.1017/S0029665108005983

Dietary n-3 PUFA have many beneficial effects on cell and tissue function and on human health. In mammals the n-3 essential fatty acid alpha-linolenic acid (ALNA) can be converted into longer-chain (LC) n-3 PUFA such as EPA and DHA via a series of desaturase and elongase enzymes that are mainly active in the liver. Human studies have identified that males and females appear to differ in their ability to synthesise EPA and DHA from ALNA, with associated differences in circulating concentrations. Based on studies of women using the contraceptive pill or hormone-replacement therapy and of trans-sexual subjects it is suggested that sex hormones play a role in these differences. The rat has been used to investigate gender differences in n-3 PUFA status since this model allows greater dietary control than is possible in human subjects. Like human subjects, female rats have higher plasma DHA concentrations than males. Rats also respond to increased dietary ALNA in a way that is comparable with available human data. The concentrations of LC n-3 PUFA in rat plasma and tissues are positively associated with circulating concentrations of oestradiol and progesterone and negatively associated with circulating concentrations of testosterone. These findings suggest that sex hormones act to modify plasma and tissue n-3 PUFA content, possibly by altering the expression of desaturase and elongase enzymes in the liver, which is currently under investigation.

Childs CE, Romeu-Nadal M, Burdge GC, Calder PC. J Nutr. 2010 Feb;140(2):245-50. doi: 10.3945/jn.109.115691. Epub 2009 Dec 9

In rats and humans, females have higher liver and/or plasma docosahexaenoic acid (DHA) content than males. We hypothesized that the effect of variation in total fat or essential fatty acid intakes on liver and plasma fatty acid composition would differ between sexes. Rats were fed a low-fat soybean oil (LFS), high-fat soybean oil (HFS), or high-fat linseed oil (HFL) diet for 20 d. There were significant sex differences in LFS rats in proportions of (n-3) and (n-6) fatty acids in plasma and liver contingent on lipid class. Significant diet x sex interactions were observed for eicosapentaenoic acid (EPA), DHA, and arachidonic acid (AA) status. HFL females had a higher proportion of EPA in plasma and liver phosphatidylcholine (PC), DHA in liver triacylglycerol (TAG), and AA in plasma PC than HFS and LFS females. These findings show that the effect of varying dietary fat intake on (n-3) and (n-6) long-chain PUFA (LCPUFA) status is modified by sex. Liver phospholipid and TAG fatty acid product:substrate ratios suggested greater Delta6 desaturase (Delta6D) activity in females than in males. The HFL diet induced higher Delta6D mRNA expression compared with the LFS or HFS diets and HFL females had 10% higher expression of Delta6D mRNA than HFL males. Together, these findings show that sex is an important determinant of the effect of variations in fat and fatty acid intake on LCPUFA status, which may have implications for recommendations for fat and fatty acid intake in humans

Das UN. Nutrition. 2002 Feb;18(2):178-88

To investigate whether there is any common link between estrogen, statins, and polyunsaturated fatty acids (PUFAs), which have similar actions and benefits. METHODS: To critically review the literature pertaining to the actions of estrogen, statins, and various PUFAs. RESULTS: Estrogen, statins, and PUFAs enhance nitric oxide synthesis, suppressthe production of proinflammatory cytokines such as tumor necrosis factor (alpha), interleukin-1, interleukin-2, and interleukin-6, show antioxidant-like and antiatherosclerotic properties, have neuroprotective actions, and by themselves or their products inhibit tumor cell proliferation and improve osteoporosis. Estrogen, statins, and PUFAs not only have similar actions but also appear to interact with each other. For instance, the binding of estrogen to its receptor on the cell membrane may be determined by its lipid content, statins and PUFAs inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, statins influence the metabolism of PUFAs, and PUFA deficiency enhances 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. Statins and PUFAs inhibit tumor cell proliferation, suppress ras activity, and may prevent neurodegeneration and improve cognitive functions such as learning and memory. This suggests that PUFAs might be mediators of the actions of statins. Estrogen boosts cognitive performance in women after menopause and may protect against Alzheimer’s disease.

CONCLUSIONS: The common link between estrogen, statins, and PUFAs may be nitric oxide. Hence, a combination(s) of estrogen or its derivatives, statins, and various PUFAs may form a novel approach in the management of various conditions such as hyperlipidemias, coronary heart disease, atherosclerosis, osteoporosis, cancer, neurodegenerative conditions, and to improve memory.