Volume 1 Number 1 February 2003


vii Preface: Nutraceutical Research & Education Now: We can’t afford to wait
Chandan Prasad, Lester Packer, Iris F.F. Benzie, Tomohito Hamazaki, Wim J. Riedel, and Keith A. Wesnes [TEXT]
viii Pearson v. Shalala, A Landmark Decesion for Nutraceutical and Functional Food Industry
Lester Packer and Chandan Prasad [TEXT]
Review Articles
1 High-dose nutraceuticals in Human immunodeficiency Virus –disease. An understudied Option?
Markus P. Look, Klaus Krämer, Juergen K. Rockstroh, Joe M. McCord, Lester Packer [ABSTRACT]
17 Blood pressure and vascular effects of soy: How strong is the evidence?
Sheila G. West [ABSTRACT]
31 Gut Metabolism and Cardioprotective Effects of Dietary Isoflavones
Max Bingham, Glenn Gibson, Nicole Gottstein, Sonia De Pascual-Teresa, Anne-Marie Minihane and Gerald Rimbach [ABSTRACT]
49 Contemporary Neuroscience Meets Traditional Medicine – Towards Understanding Ginko Biloba Neuroprotection
59 From Clinical Observations to Molecular Biology: Ginko Biloba Extract Egb 761, A Success for Reverse Pharmacology
Yves Christen [ABSTRACT]
73 Importance of Vitamin K for Bone and Vascular Health
85 Olives and their production waste products as sources of bioactive compounds
Francesco Visioli and Claudio Galli [ABSTRACT]
89 Animal Studies Revealing Positive Dietary Effects on Cognitive Performane: A Brief Review
Research Articles
97 Risk of Multiple Micro-nutrient Deficiency in the Diet of Type-2 Diabetic Subjects
Irene M Simon-Schnass, C Rosak, P Rösen, E Olano-Martin, And L Packer [ABSTRACT]











Current Topics in Nutraceutical Research, Volume 1, Number 1, pp. vii (2003)

“Let food be your medicine and medicine be your food”.
- Hippocrates

As a society, we are living longer, becoming more health-conscious and seeking new ways to improve the quality of life. Each year, millions of new consumers are seeking alternatives to Western medicine for disease prevention and often to supplement or replace conventional therapies for a variety of illnesses. Western and Traditional medicine are now at a crossroad. The future holds great promise for merging and appropriately coordinating medical research and practice to bring together the best of both worlds for management of health and disease.

It is estimated that the nutraceutical market worldwide will exceed US$ 50 billions by 2004; of this about US$ 23 billions will be spent by US consumers alone. This is not an inconsequential amount when we compare it with an expenditure of US$ 150 billions on prescription drugs in 2001 in the US. This increase in consumer expenditure is anticipated to develop new markets for Nutraceuticals, functional foods and beverages and to provide challenges for the future of the food industry. The new techniques of genomics and proteonomics will provide new insights into the health effects of nutraceticals and help grow the market.

Thousands of traditional medicines have been described with origins in Oriental medicine and tribal cultures in all continents throughout the world. Indeed knowledge about some of these remedies is being lost in developing countries through urbanization of societies. The list of Herbal remedies is staggering and many books, pharmacopoeia’s and an extensive literature have documented its existence and reported on their beneficial effects toward health and well-being, disease prevention and treatment. However, in most instances the active principles and their mechanisms of action are not well understood. There is also unprecedented interest throughout the world in bringing to light the molecular basis of the biological activity of traditional remedies that have been used for centuries and in some cases for thousands of years.

In recognition of the rise in consumer interest in Alternative and complementary forms of medicine, as well as their potential to become cost-effective and non-invasive therapies, the U.S. National Institutes of Health has organized an Office of Dietary Supplements. This office together with the National Center for Complementary and Alternative Medicine supports basic and clinical research efforts to verify health claims and to determine the molecular basis of health effects. However, the efforts of the government in research and education in this area remains inadequate, and the industry contribution to this effort virtually non-existent. Government can play an important role in encouraging the industry to invest in research enterprise by granting propriety or exclusive product rights. In return, the government can regulate and demand safe and high quality nutraceuticals for the consumer. In summary, if we were to protect the industry and at the same time draw maximal benefit from nutraceuticals, there are important and complementary roles to be played in protecting the consumer by academia, industry, and government. This role can be summed up in one phrase, “The Promotion of Research, Education, Safety, and Quality Assurance”.

Current topics in Nutraceutical Research will assume a role of nutraceutical educator by providing a forum for review of the issues involved in the wider use of traditional and herbal products for health. The remit of this forum will cover the critical evaluation of nutraceuticals in their use for health maintenance and the treatment of disease, the identification of potential adverse effects, issues regarding chemistry and methods preparation, the proper design and conduct of clinical trials to evaluate the efficacy of nutraceuticals, the challenges that lie ahead in combining traditional and western medicines, and their role in National health care and public policy issues Our failure to educate may lead to inferior products and consumer frustration. Therefore, we seek to invigorate our research and education efforts.

The journal is edited by a group of six associate editors representing three continents, with the help of a thirty-one member editorial board representing twelve countries and every conceivable area of expertise. In addition, a journal advisory board of twenty-one members who mostly come from the nutraceutical industry will advise the editorial board on relevant subjects to review. At present, there is no single peer-reviewed journal devoted to the critical evaluation of scientific data on nutraceuticals and health. We hope the journal, Current Topics in Nutraceutical Research, will fill this void.

Chandan Prasad, USA
Lester Packer, USA
Iris F.F. Benzie, Hong Kong
Tomohito Hamazaki, Japan
Wim J. Riedel, The Netherlands
Keith A. Wesnes, United Kingdom
Associate Editors





Pearson v. Shalala, A Landmark Decesion for Nutraceutical and Functional Food Industry
Virtually simultaneous with the time of going to press with the first issue of Current Topics in Nutraceutical Research, we have learned of a court decision, which is of momentous importance for the Nutraceutical Industry. Herewith, we reproduce with permission this information in its entirety (See Box below). Subsequently, it has been learned that the United States District Court for the District of Columbia has granted a motion for a summary judgment against the FDA to permit an antioxidant/cancer risk reduction claim.

These events bear important tidings for future developments of science-based nutraceuticals and functional foods. Markets, where health claims backed by scientific evidence are allowed, have experienced significant growth in terms of development and marketing of products in recent years. Also, decisions of Pearson v. Shalala brings a greater awareness and responsibility for the nutraceutical industry as well as the academic community to provide a better scientific understanding of the safety and health benefits that may be derived from foods as well as how to determine and assure product quality.

Lester Packer
Chandan Prasad
Associate Editors
December 28, 2002

CONTACT: Claudia A. Lewis-Eng; Jonathan W. Emord (202-466-6937) jemord@emord.com

WASHINGTON, D.C.-On December 18, 2002, FDA Commissioner Mark McClellan announced a major initiative to make available more concerning the effects of dietary supplements and foods on the prevention of disease. The decision is an abrupt departure from the agency's long held view that no nutrient-disease claims should be allowed for foods or dietary supplements unless proven to a near conclusive degree. In 1999, the United States Court of Appeals in a landmark ruling, Pearson v. Shalala, ordered FDA to allow claims for dietary supplements backed by credible, yet inconclusive scientific evidence. For the past three years, FDA has refused to follow that order only to be sued by clients of this firm again and again.

Today FDA abandoned its prior position and agreed to implement Pearson fully. Indeed, FDA announced that it would apply the decision not only to dietary supplements but also to conventional foods. This will mean that far more information about the actual and potential health benefits of dietary supplements and foods will reach consumers than ever before. The decision is nothing short of revolutionary.

The firm Emord & Associates represented the successful Plaintiffs in Pearson v. Shalala and those who have challenged FDA's failure to implement the decision. The firm also filed comments in a recent First Amendment notice and comment proceeding at FDA recommending many of the changes now brought about by the FDA's action.

Emord says: "Today's decision is a momentous victory for those who cherish freedom. As never before companies will be able to inform consumers of the disease risk reducing and preventive effects of certain foods and dietary supplements. Consumers, in turn, will be able to modify their food choices to improve their health and longevity. There may be no action more important for the health and welfare of American consumers than the one taken by Commissioner Mark McClellan and Chief Counsel Dan Troy. This is a wonderful holiday gift for the American people."

Tim Bolen
JuriMed - Public Relations and Research Group





Current Topics in Nutraceutical Research, Volume 1, Number 1, pp. 1-16 (2003)

1Markus P. Look*, 2Klaus Krämer, 1Juergen K. Rockstroh, 3Joe M. McCord, 4Lester Packer
1Department of Internal Medicine I, University of Bonn, Sigmund Freud-Strasse 25, 53105 Bonn, Germany; 2BASF Aktiengesellschaft, Fine Chemicals, 67056 Ludwigshafen, Germany3 ;Webb-Waring Institute, University of Colorado Health Sciences Center, Denver, Colorado, USA; 4Dept. Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles, USA

ABSTRACT: This hypothesis paper outlines the rationale for introduction of nutraceutical-therapy into the context of modern human immunodeficiency virus disease management. Proinflammatory and oxidative stress induced by the immune response mechanisms directed against opportunistic infections and by the human immunodeficiency virus itself are important driving forces in human immunodeficiency virus disease progression. Special emphasis is given to the relation between micronutrients and the pathophysiological features of the disease. In addition, we intend to make an obvious paradox more public, i.e., since 1985 numerous review articles have been published, in which the authors for the very most suggested to perform large-scale trials investigating antioxidants and other micronutrients in human immunodeficiency virus-disease, whereas, surprisingly few well-controlled intervention studies have been actually performed. Possible reasons are discussed. Finally, five modules are introduced, which could constitute a nutraceutical-regimen that might be used in combination with standard antiretroviral drug therapy.





Current Topics in Nutraceutical Research, Volume 1, Number 1, pp. 17-30 (2003)

Sheila G. West Department of Biobehavioral Health, 315 Health and Human Development Building East, University Park, PA, 16802, USA.

ABSTRACT: Epidemiologic studies suggest that consumption of soy foods lowers the risk of cardiovascular disease. There is a large body of evidence from clinical studies showing that soy protein lowers low density lipoprotein cholesterol, an important risk factor for coronary heart disease. Recent research has examined whether soy protein and soy phytoestrogens have beneficial effects on blood pressure and on vascular function. This paper reviews the literature on dietary factors that regulate blood pressure, and provides a detailed critique of 21 clinical studies examining the effects of soy foods, soy protein isolate, and soy phytoestrogens on blood pressure and vascular function. Of the 12 clinical studies that examined the effects of soy foods or soy protein on blood pressure in healthy adults, 8 reported a statistically significant reduction in blood pressure (ranging from 2 to 8 mmHg) during consumption of soy products. The largest reductions in blood pressure (-16 to –18 mmHg) were reported in a study of adults with clinically significant hypertension. Although isoflavone supplements do not reduce blood pressure, they may have important effects on vascular function. This paper highlights important technical issues in measuring blood pressure and vascular function, and offers suggestions for future research.





Current Topics in Nutraceutical Research, Volume 1, Number 1, pp. 31-48 (2003)

Max Bingham, Glenn Gibson, Nicole Gottstein, Sonia de Pascual-Teresa, Anne-Marie Minihane and Gerald Rimbach School of Food Biosciences, The University of Reading, Whiteknights PO Box 226, Reading RG6 6AP, UK

ABSTRACT: The Food and Drugs Administration (FDA) has recently approved a health claim for soy based on clinical trials and epidemiological data indicating that a high soy consumption is associated with a lower risk of coronary artery disease. Soy products contain a group of compounds called isoflavones, with genistein and daidzein (and their corresponding glycosides) being the most abundant. Isoflavones undergo extensive metabolism in the gut lumen prior to absorption. The chemical form in which the isoflavones are ingested, the activitity of specific intestinal microflora and the presence of other dietary factors are important determinants of isoflavone metabolism, bioavailability, and subsequent biological activities. Current research has begun to elucidate the species and activities of various bacteria that may be responsible for the metabolism of isoflavones to their more protective secondary metabolites. However underlying molecular mechanisms have not yet been clearly established. A number of cardioprotective benefits have been attributed to dietary isoflavones including a reduction in LDL cholesterol, an inhibition of pro-inflammatory cytokine, cell adhesion protein and nitric oxide production, potential reduction in the susceptibility of the LDL particle to oxidation, inhibition of platelet aggregation and an improvement in vascular reactivity.





Current Topics in Nutraceutical Research, Volume 1, Number 1, pp. 49-58 (2003)

Yuan Luo, Laboratory of Cellular and Molecular Neuroscience, Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, MS 39406. USA

ABSTRACT: Use of alternative and complementary medical approaches, including herbal remedies, has increased substantially in the last decade, both in the United States and globally. The disease prevention theory associated with traditional Eastern medicine has the potential to both increase quality of life and reduce health care costs in Western societies. Action mechanisms of herbal remedies are, unfortunately, poorly understood. Moreover, Eastern medicine has developed within a theoretical and cultural framework that is significantly different from that of conventional Western medicine. For these reasons, understanding the mechanisms of action of herbal remedies is potentially more challenging, but not unapproachable. Application of contemporary neuroscience theories and available methodologies might help provide a better understanding of the effectiveness of traditional Eastern medicine. The purpose of the present paper is to provide an overview of how a complex herbal product, an extract from Ginkgo biloba has been studied with the tools of contemporary neuroscience.





Current Topics in Nutraceutical Research, Volume 1, Number 1, pp. 59-72 (2003)

Yves Christen
Beaufour Ipsen Pharma, 24 rue Erlanger, 75016 Paris, France

ABSTRACT: Ginkgo biloba extract, EGb 761, is a drug used to treat cerebral insufficiency and other brain disorders (including dementia), neurosensory deficiencies and peripheral circulatory disturbances. First marketed in 1975, it has been subjected to numerous clinical, pharmacological, and molecular studies. The synthesis presented here demonstrates the consistency of the data about its multiple effects in the treatment of age-associated cognitive disorders. Current research on EGb 761 is not limited to its effects in humans. Although the development of drugs normally proceeds from basic research to the study of clinical effects, EGb 761 provides an example of the reverse procedure: its clinical applications have been studied before the molecular mechanisms involved were investigated. I propose to call this mode of research “reverse pharmacology”, by analogy with “reverse genetics”, and I show how it applies to the study of the cognitive and anti-dementia effects of EGb 761.





Current Topics in Nutraceutical Research, Volume 1, Number 1, pp. 73-84 (2003)

Cees Vermeer
VitaK and Cardiovascular Research Institute (CARIM), University of Maastricht, PO Box 616, 6200 MD Maastricht, The Netherlands

ABSTRACT: Apart from its well-established role in haemostasis, new functions for vitamin K have been discovered during recent years. In this paper we focus on the contribution of vitamin K to bone health and its role in the regulation of tissue calcification. Whereas relatively low intakes of vitamin K are required for maintaining normal haemostasis, arguments are provided suggesting that higher intakes are needed for optimal bone health. Subjects prone to develop a sub-clinical vitamin K-deficiency of bone tissue are those with rapid bone turnover such as infants and children during growth, and postmenopausal women. Bone metabolism is a complex process depending on many dietary and other factors. Preliminary data support the concept of strong synergistic effects between supplements of minerals, vitamin D and vitamin K. The optimal dose for nutritional vitamin K has not yet been established, and it is suggested that strategies for bone loss reduction should aim at vitamin K intakes comparable with those in the highest quartile of the Rotterdam Study population, i.e. 375 mg/day for K1 and 45 mg/day for K2. Vitamin K is also involved in the inhibition of vascular calcification, and the many similarities between artery calcification and bone formation are discussed. In cell culture systems and experimental animal systems for tissue calcification, K2 seemed to have higher activity than K1, but at this time it remains to be awaited whether the same will be true for prevention of bone loss in humans. Most clinical studies have used bone densitometry and biochemical markers for bone metabolism to investigate potential effects of vitamin K on bone quality. However, insufficient data are available to decide whether increased vitamin K intake will result in fracture risk reduction.





Current Topics in Nutraceutical Research, Volume 1, Number 1, pp. 85-88 (2003)

Francesco Visioli and Claudio Galli
University of Milan, Department of Pharmacological Sciences, University of Milan, Milan, Italy.

ABSTRACT: Olives are rich in phenolic antioxidants that, during olive oil production, end up either in olive oil or, for their major part, in the waste water. In fact, during the malaxation process, i.e. the continuous washing of the olive paste with warm water prior to the procedure of separation of the oil from the paste, a considerable amount of water is employed. This water, in addition to that endogenously contained in the olives, make up to 50% of the total yield of the olive paste (olive oil amounts to ~ 15%) and is named “waste water”. In fact, due to the failure to develop a suitable end-of-pipe treatment technology, olive mill waste waters (OMWW) are currently discarded by olive oil manufacturers. In vitro, phenolic components of olive oil and its waste water have been shown to exert potent biological activities including, but not limited to, antioxidant actions. Catechols from olive mill waste water can be isolated in rather pure form: 10-20 per cent of the total phenols is recovered and the only bioactive catechol is hydroxytyrosol. This ortho-diphenol has been shown by several authors to exert potent antioxidant and additional biological activities, both in vitro and in vivo.





Current Topics in Nutraceutical Research, Volume 1, Number 1, pp. 89-96 (2003)

CR Markus1,2
1University of Maastricht, Dept. of Experimental Psychology; Maastricht, The Netherlands;
2Organization for Applied Scientific Research (TNO), Department of Target Organ Toxicology, Zeist; The Netherlands.

ABSTRACT: There has been an increased interest in the positive effects of dietary nutrients and supplements such as herbs, fatty acids and vitamins as possible alternative cognitive enhancing products. However, in human studies clinical improving evidence is still missing and the mechanisms of action of these apparent promising functional foods are still poorly understood. The present paper summarizes animal studies that have frequently shown positive effects of herbs, fatty acids and vitamins on learning and memory. These findings may provide additional knowledge about the mechanisms involved in the effect of dietary constituents on the brain and behavior of action.





Current Topics in Nutraceutical Research, Volume 1, Number 1, pp. 97-104 (2003)

Irene M Simon-Schnass1, C Rosak2, P Rösen3, E Olano-Martin4, and L Packer5
1Nutrisan®, Private Institute for Nutrition Research Dr. Irene Simon-Schnass, D-82377 Penzberg, Federal Republic of Germany; 2Sachsenhausen Hospital, Diabetology, D-60594 Frankfurt/Main, Federal Republic of Germany; 3Diabetes-Forschungsinstitut, Heinrich-Heine-Universität Düsseldorf, D-40225 Düsseldorf, Federal Republic of Germany; 4Pulmonary and Critical Care Medicine, Internal Medicine, University of California Davis, Surge 1, Rm 1121, Davis, CA 95616; and 5University of Southern California, School of Pharmacy, Health Sciences Campus, 1985 Zonal Avenue, Los Angeles, CA 90033

ABSTRACT: Type-2 diabetes subjects show an increased risk of multi-morbidity. To avoid additional risks from nutritional deficiencies the diabetes associations require that the diets meet the recommended intake for all nutrients. The aim of this study was to determine whether this recommendation is really followed in practice. Three-day food records of 130 persons with type-2 diabetes, of which 62% followed a weight reduction program, were analyzed to determine the intake of 22 micronutrients. Mostly, the Dietary Reference Intakes (DRIs) of vitamins and minerals set by the Food and Nutrition Board were used as references values. Manganese was the only nutrient that was available in sufficient amounts in all of the subjects´ diets. Vitamins D and E, folate, calcium, and iodine intakes were less than 50 % of the DRIs in 60 to 90% of the subjects. More than half of the vitamins and minerals from the diets of subjects on a weight reduction program tested lower than 50% of the DRIs. In conclusion, there are multiple deficits between the actual and the recommended nutrient intakes in diets of persons with type-2 diabetes. In order to meet the DRIs, the subjects would have to adjust their diets and/or use a dietary supplement formulated to provide micronutrients to complement their food intake.