The growing science of lignans' health benefits
their human metabolites has grown with media coverage of studies
proposing health benefits. But where does the science stand at
Plant lignans come from sources such as flax seed, whole grain cereals, berries, vegetables and fruits. Several hundred individual lignans have been discovered but the main research has focussed on lignans from flaxseed (Linum usitatissimum), with a small but growing number of studies on lignans from Norwegian spruce bark (Picea abies). To understand how these lignans benefit health it is important to understand the chemistry and biochemistry of these compounds. The main lignan from flaxseed is secoisolariciresinol diglucoside (SDG), with Acatris' SDG dominating the flax lignan market. When SDG is ingested it is metabolised by microflora in the human gut into the mammalian lignans, enterodiol (END) and enterolactone (ENL). These two metabolites are then absorbed from the gut and transported to the liver where they undergo further reactions before entering circulation. According to Acatris, a 50 mg daily dose of SDG is sufficient to deliver the health benefits associated with flax lignans. Both END and ENL are found in plasma mainly as free compounds, mono- and disulfates, in the urine mostly as monoglucurinoides, and in the faeces as free compounds. Norwegian spruce bark, on the other hand, offers the lignan, 7-hydroxymatairesinol (HMR), which has been commercialised by Swiss company, Linnea. HMRLignan is metabolised differently in the body, forming mostly enterolactone (ENL) and some 7-hydroxyenterolactone (HENL), but no enterodiol. Linnea says that 10 to 40 mg of its 7-hydroxymatairesinol lignan can elevate the enterolactone level to the same degree as three tablespoons of lignans from unground flax seed. Because metabolism of the lignans is dependent not only on the nature of the lignan, but also on the health of bacteria in the human intestinal tract, some differences between people do exist. Antibiotic administration also impedes the action of the microflora to metabolise the plant lignans. A number of studies have reported links between increased dietary lignan intake, and/or increased levels of enterolactone and/or enterodiol and protection/ reduced risk of a wide range of conditions, most notably breast cancer, prostate cancer, and reduced hair loss. A recent epidemiological study from Germany (European Journal of Cancer Prevention, Vol. 15, pp. 225-232) reported that average plasma enterolactone levels of 12.96 nanomoles per gram were associated with a 58 per cent reduction in breast cancer risk, while average plasma enterolactone levels of 24.96 nanomoles per gram was associated with a reduction of 62 per cent. When calculated in combination with lignan intake, similar results were observed. A high intake of enterolignans (enterodiol and enterolactone) on the basis of dietary intake (846 micrograms per day) combined with a high plasma enterolactone level was associated with a reduction in the risk of breast cancer of 64 per cent. Some claim that such benefits are not backed up by epidemiological studies. A recent review by Italian scientists (Clinica Chemica Acta, Vol. 365, pp. 58-67) reported that 10 epidemiological studies linking enterolactone levels and breast cancer risk were 'conflicting' - six reported positive results, and four reported null results. But the studies reviewed were severely limited by, most notably, providing no information on antibiotic use, being observational, and based on (in some cases) dietary recall from the subjects. Jocelyn Mathern, RD, technical specialist with Acatris told NutraIngredients.com at the start of June that Acatris is expecting results of a study in women in Australia looking at the effects of its flaxseed extract, LinumLife, on markers of breast cancer. "We hope to confirm that SDG, the main flax lignan, is largely responsible for the beneficial effects seen in previous flaxseed studies looking at breast health", said Mathern. The study is investigating the effects of LinumLife, which delivers the needed 50 mg SDG dosage, on oestrogen metabolites in postmenopausal women. "They are also determining the length of time it takes flaxseed to exert its positive effects on estrogen metabolism. Studies with flaxseed have shown that 5 to 10 grams of flaxseed can increase the production of good or 'protective' estrogen, which is associated with the decreased risk of breast cancer," said Mathern. A growing number of studies have also linked increased lignan intake, or increased enterolactone and enterodiol levels, with reduced risk of prostate cancer. A recent in vitro study using HMRLignan reported that both enterolactone and hydroxymatairesinol increased programmed cell death (apoptosis) in a dose-dependent manner. Robin Ward, vice president of marketing for Linnea, told NutraIngredients.com at the time of this report (May 2006) that the next step to examine the effects of HMRLignan on prostate cancer was to undertake animal studies. While such experiments have not yet been performed using HMRLignan, research presented last March at the 61st Flax Institute of the United States Meeting, is reported to have shown for the first time that flaxseed lignans reduced prostate enlargement in a rat model. "Research indicates that men who eat more foods containing flax lignans may have a lower risk of prostate cancer," said Mathern. The third area where the science is considerable and promising concerns hair loss. An intervention trial that supplemented the diets of male subjects with 250 mg of LinumLife reported that 90 per cent of the volunteers had improvements in their hair loss problem, and 50 per cent reporting a decrease in oil secretion in the scalp. Preliminary results are also staring to emerge that link lignan intake or increased enterolignan levels to reduced risks of colorectal and/or lung cancer. Mathern told NutraIngredients.com: "There is some emerging data with regards to lung and colorectal cancer, but the majority of studies are observational, linking lignans to these health benefits. There have not been any intervention studies in humans yet." Indeed, only recently NutraIngredients.com reported on a retrospective study that appeared to show increased levels of enterodiol and enterolactone were associated with a reduction of colorectal cancer of about 40 per cent. In this study, the researchers accounted for antibiotic use, but the study is still limited by being retrospective. "It will be interesting to see how science evolves in this area," said Mathern. The mechanism(s) behind the benefits of the lignan metabolites has been linked to the weak (anti-)oestrogen-like activity of enterolactone and enterodiol, but the exact mechanisms involved need to be the focus of mechanistic studies. Jocelyn Mathern agreed: "There is still more to learn about all of the mechanisms involved in the actions of flax lignans as well as optimal dosage for the various health conditions." According to the US National Institutes of Health's randomized trial records, two trials have recently finished investigating the health effects of flax lignans. The first, a phase III trial entitled "Exercise and Flax-Based Nutritional Supplementation for Lowering Cholesterol" was scheduled for completion in May of this year. The trial, led by Philip Chilibeck, PhD from the University of Saskatchewan in Canada, investigated the effect of a daily dose of 500 mg flax lignan for people with high cholesterol levels (hypercholesterolemia). The second trial, said to have finished at the end of 2005, entitled, "Macrobiotic Diet and Flax Seed: Effects on Estrogens, Phytoestrogens, and Fibrinolytic Factors" was a phase II trial with one group of subjects assigned to the American Heart Association step 2 diet plus 10 g/day flax seed. This study was led by Dr Lawrence Kushi from Columbia University in New York. One on-going trial that considers enterolactone levels of 300 subjects is listed on the International Standard Randomised Controlled Trial (ISRCT) Number Register, entitled, "Randomised controlled trial to test the impact of increased consumption of wholegrain foods on cardiovascular disease (CVD) risk: The WHOLEheart study." The study, due for completion in April 2007, is led by Dr Chris Seal from the University of Newcastle upon Tyne, UK.