The scoop on soy

The American Heart Association's recent sweeping statements against soy are biased given there are clearly dose-, time-, gender- and age-dependent effects of soy supplementation. Mark J Tallon, PhD, explains

Healthy. Cardio-protective. Clinically efficacious. These are just some of the words that are brought to mind when you hear the word 'soy.' However, if you were to read the recent damning guidelines released by the American Heart Association's (AHA) nutrition committee, you may be forgiven for believing otherwise. Concluding this paper, the authors of the AHA study comment, "The use of isoflavone supplements in food or pills is not recommended" and "Earlier research indicating that soy protein has clinically important favourable effects as compared with other proteins has not been confirmed."1

These sweeping statements are highly biased given there are clearly dose, time, gender and age-dependent effects of soy supplementation. If these researchers were to look for studies using isoflavone contents >100mg/day in postmenopausal women, the outcomes and recommendations would be highly positive. In contrast to the AHA publication, researchers from a pan-European multidisciplinary team (EU-funded project Phytohealth) suggest some beneficial effects of soy on not only lipid markers of cardiovascular risk but also reducing hot flashes.2

Although a full report on the limitations of the AHA study is not possible within the constraints of this article, I will highlight one further point made by the EU review. The authors of the AHA review commented that too few randomised, controlled trials exist to reach a conclusion on many of the health benefits proposed for those consuming soy. As such, I endeavour to cover the most recent selection of soy research presented (nearly a year post data collection for AHA and EU review data) at the Experimental Biology conference in San Francisco in April 2006. This research currently in the process of submission to the world's leading journals provides further evidence, insight and efficacy into the many emerging applications of soy as one of the industry's leading functional foods.

Soy and sex hormones
In a prolonged debate among protein biochemists and health enthusiasts alike, the influence of soy protein on sex hormone modulation has been hotly debated. The purpose of the following study was to compare the effect of ingesting four types of protein supplements over a 12-week period at a dose of 50g/day in combination with resistance training on body composition and sex hormones in males.3

Supplementation consisted of soy protein concentrate; soy protein isolate; soy plus whey isolate (50/50 mixture); or whey mixture (50/50 of concentrate and isolate). Supplements were used whilst undertaking resistance-training sessions three times per week. Results from the study show significant increase in lean body mass independent of the protein source. No significant differences occurred between groups for changes in per cent body fat, lean body mass, body weight, total or free testosterone, estradiol, sex hormone binding globulin, or the testosterone : oestrogen (T:E) ratio. However, within the group analysis, researchers identified a significant increase in the T:E ratio for soy plus whey and a significant estradiol decrease for whey.

Daily supplementation of soy or whey results in increases in lean body mass

These authors concluded that daily supplementation of soy, whey or soy plus whey results in similar increases in lean body mass. They also comment that these supplementation regimes do not negatively affect testosterone or estradiol levels in males engaged in a weight-lifting program. This study points to the beneficial effects combined protein sources can have over single supplementation strategies for modulating sex-hormone levels. These outcomes may result in greater gains in strength or health over an extended period of time.

Bone health
Osteoporosis prevalence, currently at 44 million, is expected to rise to 52 million adults aged over 50 years old by 2010.4 As such, the search for successful and low-cost treatments has become big business. This recent study determined if soy isoflavones (IF) (following lipopolysaccharide [LPS]-induced chronic inflammation) could prevent development of bone and cardiovascular disease pathology in mice.5

In phase one of the study, 66mcg LPS/kg/day produced the greatest decrease in lymphocytes and increase in neutrophils (NEU). In phase two, mice supplemented with 0, 200 or 800mg IF/kg diet. Isoflavones were fed starting two weeks prior to the 30mg/day LPS challenge. LPS induced perivascular fibrosis and lymphocyte infiltration consistent with early-stage cardiovascular disease, but 200 and 800mg IF protected against these changes.

Lipopolysaccharides decreased the trabeculae number, reduced trabecular bone volume (this makes up the bulk of the interior of most bones, including the vertebrae) in the 0 and 200mg IF groups, but 800mg IF provided protection against this reduction. These results suggest IF may attenuate negative effects of chronic inflammation on both bone and cardiovascular health indices.

Additional work regarding soy isoflavones and bone health has been carried out by researchers from Taipei Medical University. These researchers performed an open-labelled, self-controlled pilot study undertaken to determine the effects of one year of high-dose soy isoflavone intake in postmenopausal Taiwanese women.6 Forty-three women aged 45-67 years were randomly assigned into three groups for a one-year intervention trial. Groups consisted of 100mg/day isoflavone (IF100); 200mg/day isoflavone (IF200); and control.

Results indicate a positive change of bone formation patterns with IF supplementation

Following analysis of the structural and biochemical metabolism of bone, results indicated that the decrease in bone mineral density was significant for lumbar vertebrae and femoral neck in the control group compared to IF100 and IF200. 6 Surprisingly, the bone mineral density of L1-3 was significantly elevated in the IF100 group; however, there were no consistent responses in the IF200 group. The percentage change at L1-3 (lumbar region of spine) was less in the IF200 group compared to the IF100 group.

Results generally indicate a positive change of bone formation patterns with IF supplementation. A protective effect of IF100 on oestrogen-related bone loss was observed.6 Based on this data, IF100 for one year can be beneficial in decreasing bone-density loss, giving credence for further confirmatory studies in this area.

Lipid metabolism
Adipose tissue is now considered an endocrine organ in addition to the traditional role of energy storage. Adipocyte (fat cell) functionality has recently been defined as 'lipogenesis-lipolysis homeostasis.' Obesity-related hypertrophy of adipocytes affects normal adipocyte function, with consequences including but not limited to lipotoxic disorders. Recent evidence points to enhancement in leptin secretion following soy consumption and high-fat diets.7 Other mechanisms behind soy's possible obesity influencing effects are discussed in the following two studies.

In the first study, the aim was to assess if soy protein can prevent adipocyte hypertrophy in rats fed a high-fat diet, and to investigate the biological mechanisms behind any such change.8

The results showed that after 180 days, rats fed soy protein had a significant reduction in adipocyte number per area, and lower serum leptin concentrations compared to rats fed the casein diet. Perilipin mRNA (perilipin is a modulator of adipocyte lipid metabolism) concentration was higher in rats fed soy protein and associated with lower serum free fatty acid concentration.

These results suggest that soy-protein intake reduces adipocyte hypertrophy and increases perilipin expression. Because perilipin and leptin are involved in the development and maintenance of adipose tissue, these pathways seem to be the most likely target for soy's potent influence on fat metabolism. These physiological changes may in turn reduce free fatty acid release, and prevent/delay insulin resistance in obese populations.

Researchers from the University of Notre Dame have taken this research further by assessing whether it is soy protein or its isoflavones that actively influence fat metabolism.9 This second study investigated the action of soy and its isoflavones on the peroxisome proliferator activated receptors (PPARs), which are well known to play a key role in adipogenesis and adipocyte gene expression. The primary aim of the study was to assess the effect of soy and/or its isoflavones on lipid metabolism as mediated through the PPARalpha receptor pathways.

Male and female mice were obtained, including genetically altered PPARalpha knockout mice. Groups of mice were fed high-fat atherogenic diets containing soy protein +/- isoflavones and fenofibrate (a known binder of PPARalpha) for six weeks. At the end of six weeks, lipid levels and gene expression were measured.

The results demonstrated a notable reduction in serum triglycerides after isoflavone consumption. Compared with a low-isoflavone basal diet, isoflavone intake reduced serum triglyceride levels by 36 per cent and 52 per cent in female and male mice, respectively, compared to 55 per cent and 52 per cent in fenofibrate-treated mice. Isoflavones also improved serum triglyceride levels in PPARalpha knockout mice while fenofibrate did not, suggesting two different mechanisms may be affected by isoflavone intake.

Isoflavone intake resembled the action of fenofibrate on PPARalpha-regulated gene expression, although less robustly compared to fenofibrate. The authors suggest that at the levels consumed in this study, isoflavone intake alters lipid metabolism in a manner consistent with activation of PPARalpha as well as a PPARalpha-independent mechanism.

These studies suggest multiple mechanisms for the action of soy beyond just a protein source. However, interpretation of the results to humans must be applied with caution until randomised, double-blind controlled human trials are completed.

The recent damaging report from the AHA is flawed, as are so many soy studies

Soy what?
The recent damaging report from the AHA is ultimately flawed, as are so many soy studies, because the impact of equol (4',7-isoflavandiol) production in subjects should always be taken into consideration. Equol is metabolized from daidzein (a primary isoflavone found in soy) by bacterial flora within the intestines. Between 30-50 per cent of people are able to produce equol naturally, and this can be even higher in first- compared to third-generation Japanese. 10 Because equol is a nonsteroidal oestrogen, its influence on many of the health conditions soy claims to treat must be taken into consideration when assessing the total impact of soy supplementation strategies.

The influence of equol may be the reason for the disparity amongst many trials on soy, and by factoring in this issue in future studies we may be able to further enhance the credibility of soy as a natural product beneficial to optimal health.

Based on recent evidence it seems those habitually exposed to the greatest amounts of isoflavones metabolize them differently from the other generations within the same family. This suggests a further limitation to many soy studies beyond genetics in that a period of dietary acclimatisation must be implemented before any trial.10

By isolating the differences of equol and nonequol products to soy/isoflavone interventions, we can also come up with more efficacious guidelines for the use of soy for the population as a whole.

Although the equol issue is important, the recent crop of studies supports the use of soy, opening up additional market sectors for soy vendors to explore. By tightening up the study design of future research, I see a long and secure future for soy with qualified health claims across the North American and European markets.

Mark J Tallon, PhD, is chief science officer of OxygeniX, a London-based consultancy firm specialising in claims substantiation, product development and technical writing. Dr Tallon is also co-founder of Cr-Technologies, a raw ingredients supplier.
Respond: [email protected]

1. Sacks FM, et al. Soy protein, isoflavones, and cardiovascular health: an American Heart Association science advisory for professionals from the Nutrition Committee. Circulation 2006; 113:1034-44.
2. Cassidy A, et al. Critical review of health effects of soyabean phyto-oestrogens in post menopausal women. Proc Nut Soc 2006: 65;76-92.
3. Rubin S, et al. A randomized double-blind clinical pilot trial evaluating the effect of protein source when combined with resistance training on body composition and sex hormones in adult males. Experimental Biology 2005 (FASEB J) Late Breaking Abstracts #LB250.
4. America's bone health. National Osteoporosis Foundation 2006. Washington, USA.
5. Droke E, et al. Soy isoflavones prevent chronic inflammation-induced bone loss and coronary disease (CVD). Abstract #639.5.
6. Huang HY, et al. One-year soy isoflavone supplementation prevents early postmenopausal bone loss but without a dose-dependent effect. J Nutr Biochem. 2006; [Epub ahead of print].
7. Frigolet-Vazquez-Vela E, et al. Dietary soy protein increases adipocyte functionality in a rat model of diet-induced obesity (DIO). Abstract #393.1.
8. Torre-Villalvazo I, et al. Soy protein intake prevents adipocyte hypertrophy in rats fed high fat diet. Abstract # 393.2.
9. Mezei O, et al. Dietary isoflavone supplementation modulates lipid metabolism via PPAR{alpha} dependent and independent mechanisms. Physiol Genomics. 2006 Feb 28; [E-pub ahead of print].
10. Franke AA, et al. Urinary isoflavone excretion and soy consumption in three generations of Japanese women in Hawaii. Program/abstract # 381.20.

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