Johan Garssen, PhD, Conference Chairman
Professor Immunopharmacology and Nutrition, University of Utrecht, The Netherlands

Most pharmacologists will acknowledge that nutrition is important for good health and well-being, however, at the same time it is also considered to be a chemical nightmare with unknown effects. This has not always been the case, in the past connections between pharmacology and nutrition has been more intimate, as Hippocrates once stated, ‘Let food be thy medicine and let medicine be thy food. Only nature heals, provided it is given the opportunity’. Indeed, the ancient Greeks divided medicine into three categories: diet, pharmaceutical and surgical medicine. They were not the only ones; many so-called traditional medicinal systems followed this thinking with nutrition being used as a normal part of health prevention therapy.

In more recent times, however, particularly in the western world, nutrition and pharmacology have developed as rather separate disciplines. Faced with a rapidly developing world, nutrition has had to provide safe, healthy food with limited resources to an ever expanding population. Even today malnourishment is still a harsh reality for millions of people world-wide while many more, suffer from the deficiencies of bad nutrition.

Pharmacology, having strong roots in experimental physiology developed in the western world into a field in which biologically active compounds of either natural or synthetic origin were investigated for their properties to change organ and body functions. Following the rapid developments in synthetic chemistry during the last century its main focus shifted towards single compounds which high selectivity and potency. However, since a number of years the gap between both disciplines is narrowing, a movement that is coming from two sides.

Pharmacologists are increasingly realizing that the one disease– one target–one drug concept does not always provide the most successful cure, in particular not for chronic and degenerative diseases. This has led to new strategies for therapy and drug development, including system biology-based approaches, the principles of multi-target pharmacology , and the use of “dirty” or “promiscuous” drugs.

When it comes to understanding the subtle regulation of metabolic diseases and the complexity of pathological disturbances pharmacology can benefit from nutrition science. Vice versa, nutrition science is realizing that the principles of pharmacokinetics and pharmacodynamics provide mechanisms to understand the effects of both essential and nonessential components in our diet. The increased scientific and commercial interest in functional foods and food supplements has further intensified research and development in this area. Many food companies are actively engaged in finding new bioactive compounds that can be used in food products. Some discovery programs in the food industry resemble approaches used in the pharmaceutical world, starting with molecular targets that are not infrequently derived from drug targets. Furthermore, translational research using in vitro, in vivo and clinical studies has become the standard in both nutritional and pharmaceutical companies. Last but not least, the clinic has become increasingly aware of the power of nutrition in improving the outcome of disease or therapy.

The Pharma-Nutrition conference will be the first and foremost platform dedicated to the interface between pharma and nutrition and will aim to highlight, both from a conceptual and a clinical perspective, a number of new developments that are taking place at the interface of pharmacology and nutrition.

Reminder- Accepting abstract submissions now!

Key dates:
Abstract submission deadline: 3rd December 2010
Early bird registration deadline: 3rd December 2010

Professor Alessandro Laviano
Department of Clinical Medicine, Sapienza University, Rome Italy

Oncology Session
14.00- 15.30 Monday 18 April, 2011

Weight loss is one of the most frequently observed features of cancer patients. It is now well established that malnutrition has a negative impact on the outcome of cancer patients, in terms of increased anti-tumor induced toxicity, impaired quality of life and reduced survival. For many years, nutrition support was considered for patients with advanced cancer only in the palliative phase. However, now it is becoming widely accepted that there is a role for nutrition to play in earlier phases of the cancer patient’s journey, including the curative phase. This new approach to prevent rather that to treat malnutrition in cancer patients has prompted a series of research, which has highlighted the pharmacological role of specific nutrients.
Within the therapeutic area of Oncology, there is a lot of research currently being conducted involving nutrients, three main areas of research include:

1. Omega-3 Fatty Acids in combating inflammation

Consistent experimental and clinical research demonstrates that inflammation is one of the key pathogenic elements of cancer cachexia. In this light, the use of omega-3 fatty acids has been shown to effectively reduce inflammation and promote anabolism in animal models. Unfortunately, clinical studies yielded controversial results. The difficulty to replicate in humans the clear-cut results obtained in animal models of cancer cachexia suggest that the genetic profile of cancer patients may play a significant role in determining the clinical effects of omega-3 fatty acids. Recent data show that specific genetic polymorphisms involving the genes of proinflammatory cytokines may predict the severity of cachexia, and possibly the efficacy of omega-3 fatty acids. A promising line of investigation is the identification of biological markers which can guide the prescription of specific nutrients, thereby maximizing their effects.

2. Hyperactivation of ubiquitin-proteasome system

Muscle wasting in cancer cachexia is mainly due to the hyperactivation of the ATP-dependent ubiquitin-proteasome system. The activity of this proteolytic system is modulated by specific nutrients. In particular, the amino acid leucine has a potent inhibitory effects on the ubiquitin-proteasome system. Experimental data show that leucine effectively modulates proteolysis, and preliminary clinical results are confirmatory. However, a clear biological marker guiding the prescription of leucine is still missing.

3. Ghrelin resistance

Ghrelin is a potent orexigenic hormone. In cancer patients with cachexia, the presence of ghrelin resistance has been postulated since its circulating levels are increased yet appetite and food intake are reduced. The administration of exogenous ghrelin has been proposed as an effective strategy to increase food intake and reduce weight loss in cancer patients, with early promising results. However, recent data suggest that endogenous ghrelin production could be increased by the use of specific foods. Which of these two approaches will result more clinically effective in increasing ghrelin circulating levels?

Many other nutrients, including probiotics, fibers and carnitine have a strong rationale for their use to prevent and treat cancer cachexia. However, till now, we do not know yet which nutrient is more suitable for each cancer patient. To develop clinically relevant personalized medicine it is critical to have the contribution of experts from different disciplines; from basic science to clinical researchers, each having an important role to play in the cancer patient’s journey. In the near future we will see firstly, geneticists providing the clues on which gene should be considered when predicting the outcome of pharma-nutrition support, micorbiologists in selecting specific probiotics with potent anti-inflammatory activities, pharmacologists helping by analyzing the potential interactions between chemotherapy and nutrients, biologists assessing the differential replicative response of normal and cancer cells to nutrients, endocrinologists providing insights into the role of nutrients in maximizing the anabolic effects of anabolic hormones and finally the role of oncologists to revise their treatment schedules to integrate periods of pharma-nutrition.

Cancer itself and cancer cachexia are multifactorial diseases. It appears self-evident that a multidisciplinary approach is key in the effort to change cancer cachexia into a curable syndrome.

More will be discussed at Pharma-Nutrition 2011

Key dates:
Abstract Submission: 3rd December 2010
Early bird registration: 3rd December 2010

Professor Francesco Visioli
IMDEA-Food, Madrid, Spain

Invited Speaker Endocrinology/Diabetes/Metabolic Disease Session
Tuesday 19th April 2011

The relevance and influence of both diet and lifestyle as part of a therapeutic strategy in Metabolic Syndrome (MS) can clearly be seen in the recent IDF definition of this syndrome. It requires the presence of central obesity, plus two of the following four additional factors: raised triglycerides, reduced high-density lipoprotein cholesterol (HDL-C), raised blood pressure, or raised fasting plasma glucose level. In the more popular ATP-III definition, the presence of any three of the five mentioned risk factors is an indication of the presence of the syndrome. Plasma markers of inflammation such as C Reactive Protein (CRP) are also usually increased in patients with metabolic syndrome. Clearly all of these parameters can be influenced by diet and lifestyle and whose modulation should become an integral part of the any treatment.

Nutrition and metabolic syndrome: the link

The evidence of the role of nutrition in therapeutic treatment of MS was emphasized in a study by Esposito and colleagues. Taking 180 men and women with MS and splitting them into two groups, once made to follow a Mediterranean diet and the other a "prudent diet." At the end of the study, participants who followed the Mediterranean diet had lower total cholesterol and triglycerides and higher HDL-C, as compared with subjects allocated to the prudent diet. Finally, endothelial function improved in the Mediterranean diet group but not in the prudent diet group. The results of this study strongly suggest that a Mediterranean-style diet rich in whole grains, fruits, vegetables, legumes, walnuts, and where olive oil is the principal source of fat might strongly reduce both the prevalence of metabolic syndrome and its associated cardiovascular risk. The benefits of the diet might be explained by a reduction in the low-grade inflammation associated with the metabolic syndrome. Conversely, there are indications that indiscriminate reductions in fat intake - associated with exercise - lead to increased levels of circulating cytokines, possibly due to enhanced activity of the immune system.

Which evidence-based nutritional advice should we provide to our metabolic syndrome patients?

A careful analysis of the diet and its augmentation in relation to the dietary habits of each individual can ameliorate several contributors to the metabolic syndrome. Targeted dietary advice should always accompany pharmacological therapy of the metabolic syndrome. While every patient will likely respond differently to adjustments of the dietary regimen, an overall pattern should stress: the use of low-glycemic index carbohydrates, a high proportion of soluble fiber, the preferential use of extra virgin olive oil to dress salads and cooked vegetables, moderate alcohol consumption (within a normo- or hypocaloric diet), an increase in fish consumption possibly accompanied by supplements, and reduced salt consumption. Low compliance to dietary manipulations is often recorded, so frequent interviews and verifications of the patient’s attitude toward this non-pharmacological approach are to be integrated in the therapeutic strategy.

The importance of essential fatty acids

The human body is not able to synthesize essential fatty acids de novo (indeed, this is why they are termed “essential”). Thus, they must be consumed through the diet (or as supplements) in adequate amounts. From a metabolic syndrome viewpoint, the general practitioner and the specialist should pay particular attention to the essential fatty acids of the omega 3 (or n-3) series.

Omega 3 fatty acids are well-known hypotriglyceridemic agents, whose efficacy, at adequate dosage, is comparable with or superior to that of other synthetic drugs. Also, in addition to a net effect on trigliceridemia (which is due to several mechanisms of action), the effects of omega 3 on the other blood lipid parameters are usually of modest magnitude. In particular, omega 3 fatty acids do not significantly modify blood cholesterol, except in some patients where omega 3 actually increase total cholesterolemia. Notably, this increase is associated with an increase in LDL particle size, making them less atherogenic.

More relevant and diversified are the activities of omega 3 fatty acids on functional parameters linked to the metabolic syndrome. Among them, we find salubrious effects on blood pressure and on the production of adhesion molecules and pro-inflammatory cytokines by the arterial wall.

Olive oil: is it any special?

As of 2010, the cardioprotective activities of olive phenols are quite established, although the extent and precise nature of such actions needs further clarification. It must be underlined that the field of olive phenols and health, as related to the cardiovascular system, is very advanced (far more than that of, e.g. green tea or red wine). Approximately 20 human trials describe the superiority of phenol-rich olive oil to other vegetable oils or sources of fat. It must be also put forward that quality is essential to olive oil’s salubrious activities. Only high-quality olive oils, i.e. those whose phenolic fraction is abundant and proportionally rich in ortho-diphenols, might exert biological activities.

Other micronutrients

Often under-estimated or associated with the use of supplements of dubious efficacy, micronutrients (vitamins, minerals, phytochemicals) play crucial roles in the various cellular and molecular signaling pathways. It’s worth reminding that the near totality of enzymes needs cofactors to exert their catalytic activities. Unfortunately, the Western diet is rich in calories, but poor in micronutrients. Agronomic factors such as intensive cultures that impoverish food of micronutrients meet socio- and physio-pathological aspects such as aging, disease, unbalanced diet, malabsorption due to aging and the concomitant use of drugs. We should then distinguish between under-nutrition (unlikely in the Western world) from mal-nutrition (more frequent than thought, especially among the lower socio-economic classes).

To which micronutrients should we pay particular attention? First of all to vitamins, in particular to vitamin C, that is endowed with vasculoprotective and hypotensive properties reported by clinical trials. Further, to phytochemicals, i.e. the products of plants’ secondary metabolism. These molecules, often termed “antioxidants” because of their foremost activity, are able to modulate enzymatic activities which are very important in the area of the metabolic syndrome, including those linked to the adipose tissue.

For more discussion, join as Pharma-Nutrition in Amsterdam, 18-20th April 2010.

Professor Richard J. Wurtman
MIT, Cambridge, MA, USA

Opening speaker, Monday 18th April 2011
Neuology Chairman, Tuesday 19, April 2011

NUTRIENT: “A nutritious substance”; NUTRITIOUS: “Serving as nourishment; capable of supplying nutriment”. (Oxford English Dictionary; 1970)
NUTRIENT: “A chemical that an organism needs to live and grow or a substance used in an organism’s metabolism which must be taken in from its environment”.
(Wikipedia, 2010)

Surely all individual nutrients share the ability, if consumed in adequate quantities, to prevent the development of deficiency syndromes. However some nutrients have important additional actions, more akin to those of drugs: At doses independent of but usually higher than those required to satisfy nutritional needs they affect, for example, the rates at which the brain or other organs can produce neurotransmitters, or they can modify cellular structures or developmental processes. For example, brain levels of the amino acid nutrients tryptophan, tyrosine, threonine, histidine, or glutamine can control he rates at which neurons synthesize serotonin, dopamine, glycine, histamine, or GABA. Similarly brain choline levels affect the production of acetylcholine and – if the choline is given along with two other nutrients (uridine and docosahexaenoic acid) - that of the phosphatides in neuronal membranes. Administration of a relatively large dose of folic acid to a pregnant woman who exhibits no evidence of folic acid deficiency can protect her fetus from developing spina bifida or other neural tube defects. Administration of dietary carbohydrates in doses that elicit significant insulin secretion can, like giving tryptophan itself, promote serotonin synthesis; affect various normal behaviors involving this neurotransmitter; and even treat a disorder – the premenstrual syndrome – that might otherwise be approached using serotonin-uptake blockers. Numerous additional examples of nutrients acting like drugs can be adduced.

In order for administration of a nutrient to affect a non-nutritional process in the brain, several intermediate changes must occur: Plasma levels of that nutrient must be “allowed” to rise (i.e., they must not be kept more-or-less constant by feedback mechanisms); a transport protein must exist that ferries the nutrient across the blood-brain barrier, and this protein must normally be unsaturated with the nutrient; and one or more of the brain enzymes which transform the nutrient Ito its biologically-active product must also be unsaturated with substrate and thus capable of generating more product when the nutrient-substrate’s brain levels rise. These criteria are indeed met for all of the nutrients named above. Thus, for example, the armamentarium of treatments that can be used to increase brain serotonin include not only drugs like MAO inhibitors but also nutrients like dietary carbohydrates and tryptophan itself. Moreover the drugs and nutrients can sometimes be used concurrently.

In contrast, the ability of most drugs, taken orally, to affect the brain need not depend on satisfying the above criteria for nutrients. This principally results from the fact that most nutrients are highly water-soluble (exceptions including, for example, the lipid-soluble vitamins), while most drugs are lipid-soluble. Also, while the proteins with which most nutrients interact to produce their effects are low-affinity enzymes, those with which most drugs combine are high-affinity receptors. Plasma levels of a typical drug (or its biologically-active hepatic metabolite) tend to be proportionate to the dose consumed and unaffected by feedback mechanisms, and the drug, by virtue of its lipid solubility, needs no transport protein in order to cross the blood-brain barrier. Lipid-soluble drugs tend to have longer half-lives than water-soluble nutrients: Thus, consumption of a protein-rich dinner has only minor effects on plasma amino acid levels by the following morning, while single doses of many drugs can cause measurable plasma levels to persist for days.

These and other aspects of the interface between pharmacology and nutrition will be discussed at the “PHARMA-NUTRITION” meeting – probably the first ever to deal broadly with this topic - which takes place in Amsterdam on April 18-19, 2011.