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Journal: Medical hypotheses


The preparation and consumption of bone broth is being increasingly recommended to patients, for example as part of the gut and psychology syndrome (GAPS) diet for autism, attention-deficit hyperactivity disorder, dyslexia, dyspraxia, depression and schizophrenia, and as part of the paleolithic diet. However, bones are known to sequester the heavy metal lead, contamination with which is widespread throughout the modern environment. Such sequestered lead can then be mobilised from the bones. We therefore hypothesised that bone broth might carry a risk of being contaminated with lead. A small, blinded, controlled study of lead concentrations in three different types of organic chicken broth showed that such broths do indeed contain several times the lead concentration of the water with which the broth is made. In particular, broth made from skin and cartilage taken off the bone once the chicken had been cooked with the bones in situ, and chicken-bone broth, were both found to have markedly high lead concentrations, of 9.5 and 7.01μgL(-1), respectively (compared with a control value for tap water treated in the same way of 0.89μgL(-1)). In view of the dangers of lead consumption to the human body, we recommend that doctors and nutritionists take the risk of lead contamination into consideration when advising patients about bone broth diets.

Concepts: Bone, Educational psychology, Human body, Attention-deficit hyperactivity disorder, Hyperactivity, Heavy metal music, Heavy metal, Broth


There are conflicting reports about the efficacy of electronic cigarettes (e-cigs) as nicotine delivery devices and smoking cessation products. In addition, smokers' responses to some nicotine dependence questions often change as they transition to exclusive e-cig use. Nicotyrine may explain these observations. Nicotyrine forms by the gradual oxidation of nicotine in e-liquids exposed to air. E-cigs aerosolize nicotyrine along with nicotine. Nicotyrine inhibits the cytochrome P450 2A family of enzymes (CYP2A) in airways and liver. These enzymes metabolize nicotine to cotinine, and then cotinine to trans 3-hydroxycotinine. In humans, nicotine is metabolized primarily by hepatic CYP2A6. We propose that e-cig users (vapers) achieve measurable serum nicotine levels when they inhale nicotine and nicotyrine together, because nicotyrine reversibly inhibits nicotine metabolism by CYP2A13 in airways. Consuming nicotyrine by any route should irreversibly inhibit hepatic CYP2A6. When CYP2A6 is substantially inhibited, nicotine clearance is delayed and nicotine withdrawal symptoms are attenuated. Small, relatively infrequent nicotine doses can then sustain satisfying nicotine levels. This theory has numerous implications for e-cig research and tobacco control. Behavioral and pharmacokinetic e-cig studies should be interpreted with attention to likely levels of nicotyrine delivery: e-cig studies may need to routinely measure nicotyrine exposure, assess CYP2A6 activity, confirm nicotine delivery, or deliberately compare unoxidized and oxidized e-liquids. The risks of nicotyrine exposure include impaired clearance of all CYP2A substrates and any effects of the metabolic products of nicotyrine. CYP2A inhibitors like nicotyrine may be useful for future smoking cessation therapy.

Concepts: Metabolism, Smoking, Tobacco, Cigarette, Nicotine, Smoking cessation, Cytochrome P450, Electronic cigarette


The hypothesis proposed is that functional disorders, such as irritable bowel syndrome, chronic fatigue syndrome and anorexia nervosa are caused by auto-antibodies to neuronal proteins induced by molecular mimicry with microbial antigens. The age incidence of these conditions, the marked female excess, increase with economic and technological advance, precipitation by infection, and the paucity of histological changes are all consistent with the hypothesis. It can be tested directly using human sera to search for cross reaction with brain proteins in model systems such as Drosophila melanogaster. The conditions might be amenable to treatment using pooled immunoglobulin. Identification and elimination from the microbial flora of the bacteria that express the cross reacting antigens should be possible.

Concepts: Immune system, Bacteria, Water, Model organism, Irritable bowel syndrome, Fibromyalgia, Drosophila melanogaster, Chronic fatigue syndrome


Medical students in the United States are taught little about nutrition and dietetics. Worse yet, their training biases them against the studies that show the power of dietary approaches to managing disease. The current approach to evidence-based medicine encourages physicians to ignore any information that does not come from a double-blind, randomized controlled trial. Yet human beings cannot be blinded to a dietary intervention. As a result, physicians are biased toward drug treatments and against dietary interventions for the management of chronic disease.

Concepts: Pharmacology, Medicine, Health, The Canon of Medicine, Systematic review, Randomized controlled trial, United States, Avicenna


Individuals with autism who show high abilities are called savants. Whereas in their brains a disconnection in and between neural networks has been identified, savantism is yet poorly understood. Focusing on astrocyte domain organization, it is hypothesized that local astrocyte mega-organizations may be responsible for exerting high capabilities in brains of autistic savants. Astrocytes, the dominant glial cell type, modulate synaptic information transmission. Each astrocyte is organized in non-overlapping domains. Formally, each astrocyte contacting n-neurons with m-synapses via its processes generates dynamic domains of synaptic interactions based on qualitative computation criteria, and hereby it structures neuronal information processing. If the number of processes is genetically significantly increased, these astrocytes operate in a mega-domain with a higher complexitiy of computation. From this model savant abilities are deduced.

Concepts: Nervous system, Neuron, Autism, Myelin, Glial cells, Gap junction, Savant syndrome, Savant


The acquisition of cognitive, sensory-motor and social emotional functions depend on a proper development of the Central Nervous System (CNS). This set of functions, known as intelligence, allows a better adaptation to the environment. In the last decades, an increase in the average of intelligence has been reported. However, such an increase cannot be observed in an equivalent way in economically and social underprivileged regions. Children from those regions are in great risk of being affected by mental retardation or impaired cognitive development. In later life they will, probably, be unable to transform and improve themselves and their communities, perpetuating the poverty of the region. Therefore, knowledge of factors involved in CNS development is a matter of health closely related to social improvement. Malnutrition throughout pregnancy and breastfeeding is clearly identifiable as a cause of damage in CNS development. Vitamin B1 (Thiamine) is a micronutrient important to the growth and maturity of the CNS. Thiamine shortcoming may affect 50% of pregnant women. Thiamine function in cerebral development is still not well known. There is a gap in the literature regarding systematical research about the blood thiamine concentration throughout the periods of gestation and breastfeeding. These studies are relevant in populations with a high level of nutritional vulnerability, because in a follow up offspring cognitive exam they could reveal if the maternal thiamine deficiency is related to child CNS impairment. This paper introduce the hypothesis that thiamine shortcoming during pregnancy and breastfeeding is directly related to cognitive impairment of child. Data about the neurophysiological role of thiamine, consequences of its shortcoming in experimental models, populations under the risk of thiamine shortcoming are presented. The hypothesis that maternal thiamine shortcoming causes damage related to child cognitive development needs to be considered. Thus, thiamine shortcoming during gestation and breastfeeding and its effects on children must be studied in many populations in order to know the magnitude of the problem and to indicate actions to overcome it.

Concepts: Central nervous system, Nervous system, Pregnancy, Embryo, Breastfeeding, Vitamin, Thiamine, Beriberi


Sporadic amyotrophic lateral sclerosis (sALS) is a fatal neurodegenerative disease with no known cause. There are many clues to suggest an environmental trigger for the disease, including reports of conjugal couples and co-localized employees that developed sALS. On the island of Guam,a very high incidence of sALS occurred among the Chamorro natives back in the 1940s and 1950s and has been linked to the neurotoxin beta-N-methylamino-l-alanine (BMAA) that is produced by cyanobacteria that live symbiotically in the roots of the cycad plant, the seeds from which were a staple of the Chamorro diet. It has been shown that BMAA was biomagnified up the food chain from the cycad seeds to the now largely extinct, indigenous flying foxes, a former delicacy of the Chamorro natives. Recent evidence suggests that long term, chronic exposure to low levels of BMAA might cause ALS in genetically predisposed individuals. Many exposure routes to BMAA have been implicated thus far, including consumption of contaminated food and exposure to water harboring cyanobacterial blooms which have the capability of producing BMAA. Aerosolization is a well documented means for bacterial or toxin exposure causing subsequent illness, as in the case of brevetoxins and pulmonary disease and Legionnaire’s disease. We hypothesize that some cases of ALS may be related to chronic exposure to the aerosolization of cyanobacteria derived BMAA from cooling towers and might explain the observation of conjugal ALS couples.

Concepts: Medicine, Bacteria, Plant, Amyotrophic lateral sclerosis, Neurodegenerative disorders, Lou Gehrig, Cycad, Lytico-Bodig disease


Oculocutaneous albinism type 2 (OCA2) is present at significantly higher frequencies in sub-Saharan African populations compared to populations in other regions of the world. In Tanzania and other sub-Saharan countries, most OCA2 is associated with a common 2.7kb deletion allele. Leprosy is also in high prevalence in sub-Saharan African populations. The infectious agent of leprosy, Mycobacterium leprae, contains a gene, 38L, that is similar to OCA2. Hypopigmented patches of skin are early symptoms that present with infection of leprosy. In consideration of both the genetic similarity of OCA2 and the 38L gene of M. leprae and the involvement of pigmentation in both disorders, we hypothesized that the high rates of OCA2 may be due to heterozygote advantage. Hence, we hypothesized that carriers of the 2.7kb deletion allele of OCA2 may provide a protective advantage from infection with leprosy. We tested this hypothesis by determining the carrier frequency of the 2.7kb deletion allele from a sample of 240 individuals with leprosy from Tanzania. The results were inconclusive due to the small sample size; however, they enabled us to rule out a large protective effect, but perhaps not a small advantage. Mycobacterium tuberculosis is another infectious organism prevalent in sub-Saharan Africa that contains a gene, arsenic-transport integral membrane protein that is also similar to OCA2. Interestingly, chromosomal region 15q11-13, which also contains OCA2, was reported to be linked to tuberculosis susceptibility. Although variants within OCA2 were tested for association, the 2.7kb deletion allele of OCA2 was not tested. This led us to hypothesize that the deletion allele may confer resistance to susceptibility. Confirmation of our hypothesis would enable development of novel pharmocogenetic therapies for the treatment of tuberculosis, which in turn, may enable development of drugs that target other pathogens that utilize a similar infection mechanism as M. tuberculosis. From an evolutionary perspective, confirmation of our hypothesis may provide another example of heterozygote advantage.

Concepts: Bacteria, Allele, Sub-Saharan Africa, Tuberculosis, Mycobacterium, Mycobacterium tuberculosis, Leprosy, Mycobacterium leprae


Long term opioid treatment results in hyperalgesia and tolerance, which is a troublesome phenomenon in clinic application. Recent studies have revealed a critical role of toll-like receptor 4 (TLR4) in the neuropathological process of opioid-induced hyperalgesia and tolerance. TLR4 is predominantly expressed by microglial cells and is a key modulator in the activation of the innate immune system. Activation of TLR4 may initiate the activation of microglia and hence a number of neurotransmitters and neuromodulators that could enhance neuronal excitability are released. Blockade of TLR4 activation by its antagonists alleviate neuropathic pain. We hypothesized that opioid antagonists such as naloxone and naltrexone, which were also demonstrated to be TLR4 antagonist, may have clinic application value in attenuation of opioid-induced hyperalgesia and tolerance.

Concepts: Immune system, Innate immune system, Toll-like receptor, Receptor, Opioid, Pain, TLR 4, Toll-like receptors


As a general observation, wet hair in cold weather seems to be a predisposing factor for sinus headache and posterior eye pain. We offer a mechanism through selective brain cooling system for this observation. Selective brain cooling (SBC) is a mechanism to protect brain from hyperthermia. Components of SBC are head skin and upper respiratory tract (nose and paranasal sinuses). Cool venous blood from head skin and mucous membranes of nose and paranasal sinuses drains to intracranial dural sinuses and provide brain cooling. Brain will be cooled very much when head skin exposes to hypothermia such a condition like wet hair in cold weather. We suggest that, in order to reduce brain cooling activity, some alterations are being occurred within paranasal sinuses. For this purpose, sinus ostiums may close and mucus may accumulate to reduce air within sinuses. Also there may be some vasomotor changes to prevent heat loss. We hypothesize that this possible alterations may occur within paranasal sinuses as a control mechanism for brain temperature control during exposure of head skin to hypothermia. Paranasal sinuses may also cool brain directly by a very thin layer of bone separates the posterior ethmoid air sinus from the subarachnoid space and only thin plates of bone separate the sphenoidal sinuses from internal carotid artery and cavernous sinuses. Because of their critical role in the SBC, posterior ethmoid air sinus and sphenoidal sinuses may be affected from this alterations more than other paranasal sinuses. This situation may cause posterior eye pain. This mechanism can explain why a person who expose to hypothermia with wet hair or a person who don’t use a beret or a hat during cold weather gets sinus headache and posterior eye pain. These symptoms could lead to an incorrect diagnosis of sinusitis.

Concepts: Sinusitis, Internal carotid artery, Common carotid artery, Respiratory system, Cerebrospinal fluid, Mucus, Upper respiratory tract infection, Headache