New articles and forthcoming conference talks by Robert E. Smith

Robert E. Smith, the author of the two-volume set Systems Thinking in Medicine and New Drug Discovery (see here and here), has published two open access articles in EC Microbiology that build upon his recent books.

The articles, The Deep Ecology of the Human Body and The Importance of the Human Microbiome in Developing and Maintaining a Healthy Neuroendocrine Immune System and Responding to Vaccinesare essential reading for anyone interested in the application of systems thinking to the physical sciences, particularly in medicine.

In addition to this, we are delighted to share news that Robert will be speaking at Todi Week on the morning of June 26th, the World Gastroenterology & Hepatology Conference in September, and then giving two talks at the World Congress and Expo on Toxicology and Pharmacology in November. Both of these two conferences are in Rome, and details of the talks that Robert will be delivering are below. 


At the World Gastroenterology & Hepatology Conference, Robert’s talk is entitled: How Do Dietary Antioxidants Really Work?

Background: The objective of this talk is to dispel myths about ‘superfoods’ and dietary supplements that many people think are quite healthy. That is, dietary phenolic compounds (like resveratrol and epigallocatechin gallate, EGCG) don’t exert their health effects by reacting directly with reactive oxygen species (ROS) and free radicals. Instead, they activate our own natural antioxidant system – the Nrf2/ARE signaling system.

Methods: An extensive review of the literature was done, along with an assay for the Nrf2-ARE system using immortalized rat astrocytes [1-3]. More details are presented in recent books [1, 2].

Lessons Learned: There is little or no scientific basis for labeling almost any food as a ‘superfood’ – especially if it’s based on its in vivo antioxidant capacity. Instead, one must use systems thinking and total quality management (TQM) to consider the entire diet and the health of the person (the system) that ingests the food or dietary supplement. Many dietary phenolic compounds exert their health effects by activating the Nrf2/ARE system. When consumed as part of a whole food, they can help prevent cancer. The dietary fiber in fruits and vegetables helps build a healthy gut microbiome. However, once cancer emerges, some of the cells can hijack this system to make them multidrug resistant. However, metformin inhibits this system and may save lives this way.

Conclusions: The only true superfood is mother’s breast milk. Breast feeding helps build a strong bond between the mother and her baby. Breast milk also contains small molecules, growth factors, hormones, lipids, carbohydrates and even healthy bacteria. This helps babies grow and develop a healthy gut microbiome. It also supports the baby’s immature immune system, and helps it mature properly. Immunoglobulins target the infectious agents encountered by the mother during the perinatal period and then target the same infectious agents that are most likely to be encountered by the baby. Breast milk contains antibodies against many harmful bacteria. At the same time, growth factors help babies and infants develop a healthy neuroendocrine immune system.


At the World Congress and Expo on Toxicology and Pharmacology, Robert’s two talks are as follows:

Potentially Deadly Dietary Supplements

Even though many dietary supplements, like folic acid, are well-known for their health effects, many supplements are potentially deadly. This includes supplements that many consider to be healthy. This includes resveratrol and EGCG, which activate the Nrf2/ARE antioxidant system. These supplements may help prevent cancer before it occurs. However, once it occurs, cancer cells can hijack the Nrf2/ARE system to make them multi-drug resistant and resistant to radiation therapy. At the same time, many dietary supplements are adulterated with banned prescription drugs, as well as illegal drugs such as amphetamine, morphine and heroin. When consumers complain about adverse effects, the US FDA and many other governments’ regulatory agencies analyze them by liquid chromatography coupled to mass spectrometry (LC-MS). When high resolution MS is used, exact masses can be obtained. When combined with the retention times of the standards, unequivocal identification is possible. However, it is wrong to assume that any government organization is trying to keep unadulterated supplements out of the hands of the public. Unfortunately, some non-scientists have written in blogs, website, magazine articles and books, that governments are in a conspiracy with researchers, physicians and pharmaceutical companies to keep people sick so they have to buy prescription drugs that the authors claim don’t work. Actually, we are all in an open collaboration to make sure that prescription drugs are safe and effective. Moreover, we do all we can to ensure that everyone has access to folic acid, which prevents birth defects and many forms of cancer. So, the differences between how prescription drugs and dietary supplements are developed and marketed will be presented. In addition, the importance of diet and lifestyle on human health and disease will be discussed. This includes recognizing that the superfood cult is dangerous. The only true superfood is mother’s breast milk.

Potentially Neurotoxic Fruits in the Annonaceae Family

Fruits, seeds, twigs and leaves of several plants in the Annonaceae family contain neurotoxic compounds called acetogenins. Overconsumption of at least one of these fruits, graviola (Annona Muricata), caused an atypical form of Parkinson’s disease on the islands of Guadeloupe, Guam and New Caledonia. This form of parkinsonism does not respond to the standard treatment with L-dihydroxyphenylalanine (L-DOPA). It is similar to progressive supranuclear palsy, but with important differences. It is characterized by L-DOPA-resistant Parkinsonism, tremor, subcortical dementia and abnormal eye movements suggestive of Progressive Supranuclear Palsy (PSP). Patients also have hallucinations and dysautonomia, which are not characteristic of PSP. Furthermore, the oculomotor abnormalities and the tremor, which is jerky, differ from what is observed in classical PSP patients. The neurotoxicity is caused by mitochondrial dysfunction. Acetogenins inhibit the mitochondrial NADH: Ubiquinone Oxidoreductase (complex-I of the respiratory chain). These compounds are lipophilic polyketides that are found in plants in the Annonaceae family. They have two toxicophores: a γ-Butyrolactone and one or more Tetrahydrofuran (THF) or Tetrahydropyran (THP) rings. There is also a long chain alkyl group on the other end of the molecule. Even though it strongly affects the physical-chemical properties of ACGs, it is not a toxicophores. Over 400 ACGs have been found in different plants in the Annonaceae family. They can be identified by Nuclear Magnetic Resonance (NMR) and liquid chromatography coupled to mass spectrometry (LC-MS). The concentrations of two of the most abundant neurotoxic acetogenins (annonacin and squamocin) have been determined in several fruits, leaves and seeds. The LC-MS method and the results of the analyses will be presented. Another serious problem will be discussed. Unfortunately, these fruits, leaves and seeds are better known for their in vitro anticancer properties. Some of them have been shown to be neurotoxic at very lower doses.


For further information, please feel free to contact Robert at Robert.smith05@park.edu. His two volumes of  Systems Thinking in Medicine and New Drug Discovery can be purchased here and here.

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