Vitamin B12 Deficiency and Brain Health.
By Renata Trister DO
Vitamin B12 has a role in red blood cell production. Deficiency states may result in pernicious anemia. B12 supports myelin (which allows nerve impulses to conduct) and when this vitamin is deficient, symptoms of dementia, multiple sclerosis, impaired gait, and sensation may appear. Vitamin B12 also has a role in psychiatric symptoms such as depression, anxiety and fatigue.
The one-carbon cycle refers to the body’s use of B vitamins as a “methylator” in DNA synthesis and the management of gene expression. There are three concepts that relate to B12’s role in chronic, neuropsychiatric symptoms:
This process marks genes for expression (like a small tag); it is also critical for detoxification and elimination of chemicals and hormones (estrogen), building and metabolizing neurotransmitters, and producing energy and cell membranes.
B12 is a primary player in the one-carbon cycle and a co-factor for the methylation of homocysteine by activated folate, to recycle it back to methionine. Subsequently, SAMe is produced, the body’s methyl donor.
Sufficient supply of an activated/bioavailable form of a vitamin (methylfolate vs folic acid) is even more necessary in the setting of gene variants such as transcobalamin II, MTHFR, and MTRR which may function less optimally in certain individuals and result in pathology under stress. An example of the importance of this is a report of death in a B12-deficient patient with genetic variants who underwent anesthesia with nitrous gas. As the B12 blood level was normal, this fatality was attributed to functional deficiency, indicating that having available B vitamins does not guarantee proper utilization. Therefore, supplementing with activated forms of B vitamins can enhance the ability to support cellular processes.
Causes of B12 Deficiency
If it is established that a person has overt deficiency (in blood) and/or they respond to treatment, it is important to also find the cause. These are some considerations:
1. Achlorhydria or low stomach acid, occurs in low thyroid function, chronic stress, aging, and – acid blocking medications.
A patient is eating foods that they are unable to properly digest and this causes local inflammation. These foods may include processed dairy, foods fried in vegetable oils, and sugars. Inflammation further perpetuates improper digestion and slow food transit. The patient feels the reflux of this immobile, poorly digested food, and this is often seen as a sign of high stomach acid. Patients begin using long-term antacids because they feel better. Long-term use is linked to pathogenic overgrowth of bacteria, fracture, and nutrient deficiency. Stomach acid is critical for triggering digestive enzymes, “intrinsic factor” for B12 absorption and managing local microbial populations.
When this kind of digestive imbalance goes unattended, B12 deficiency can occur, along with symptoms that will suggest a need for an antidepressant and the medications begin to grow.
2. Dietary Restrictions
Animal foods are primary sources of B12, although algae and fermented foods are promising options for some dedicated vegans. Stores deplete over time, and deficiency-related symptoms may present long after dietary restriction.
One of the possible mechanisms of deficient B12 absorption is pernicious anemia, an autoimmune reaction on parietal cells, associated with atrophic gastritis in the stomach.
There seems to be a powerful synergy of gluten-containing and genetically modified processed foods. This may have an impact on digestion of many. The innate immune system responds to gluten in these grains, and food fragments may pass directly into the blood stream through gated tight junctions. Direct inflammation and damage to the cells in the small intestine may result.
Genetically modified corn may be playing a part in small intestinal villous changes as demonstrated in a study of mice consuming corn oil. There is also reason to believe that Bt-toxin from Monsanto’s GMO corn plays a role in intestinal permeability as it was found in the blood of 93% of pregnant women and 80% of their fetuses. The herbicide itself also drastically changes the gut flora, killing beneficial bacteria.
5. Medications Metformin is a risk factor for B12 deficiency in some.
Treating B12 deficiency, while the underlying cause is being determined is needed. The use of the activated form of vitamin B12 is effective at improving levels. Cyanocobalamin is a synthetic form of B12 that has been bound to a cyanide molecule while hydroxy, adeno, and methyl are all forms of B12 that are found naturally, in the body. The injectable form may yield a powerful effect over the oral form. Supplements may take time to improve symptoms (30 days or so).
A. M. Ercolini and S. D. Miller (review by Jon Trister MD)
There are many identified autoimmune diseases . Multiple factors are thought to contribute to the development of immune response to self, including genetics, age and environment. In particular, viruses, bacteria and other infectious pathogens are the major postulated environmental triggers of autoimmunity.
Multiple arms of the immune system may be involved in autoimmune pathology. Antigens are taken up by antigen- presenting cells (APCs) such as dendritic cells (DCs) and macrophages and processed into peptides which are loaded onto major histocompatibility complex (MHC) molecules for presentation to T cells via clonotypic T cell receptors (TCRs). Cytolytic T cells (Tc, activated by MHC Class I on APC) can directly lyse a target, while T helper cells (Th, activated by MHC class II) release cytokines that can have direct effects or can activate macrophages, monocytes and B cells. B cells themselves have surface receptors that can bind surface antigens. Upon receiving signals from Th cells, the B cell secretes antibodies specific for the antigens. Antibody may bind its specific target alone or may bind to and activate macrophages simultaneously via the Fc receptor.
There are multiple mechanisms by which host infection by a pathogen can lead to autoimmunity.The pathogen may carry elements that are similar enough in amino acid sequence or structure to self-antigen that the pathogen acts as a self-‘mimic’. Termed ‘molecular mimicry’, T or B cells that are activated in response to the pathogen are also cross- reactive to self and lead to direct damage and further activation of other arms of the immune system. The pathogen may also lead to disease via epitope spreading. In this model the immune response to a persisting pathogen, or direct lysis by the persisting pathogen, causes damage to self-tissue. Antigens released from damaged tissue are taken up by APCs, and this initiates a self-specific immune response. ‘Bystander activation’ describes an indirect or non-specific activation of autoimmune cells caused by the inflammatory environment present during infection. A domino effect can occur, where the non-specific activation of one arm of the immune system leads to the activation of other arms. Lastly, infection may lead autoimmunity through the processing and presentation of ‘cryptic antigens’. In contrast to dominant antigenic determinants, subdominant cryptic antigens are normally invisible to the immune system. The inflammatory environment that arises after infection can induce increased protease production and differential processing of released self-epitopes by APCs.
Coxsackievirus B (CVB) is the most common cause of infectious myocarditis. Infectious virus and viral RNA can be isolated from patients’ hearts.CVB3 can cause myocarditis in mice; in most mouse strains, the virus titre peaks at day 4 post-infection and is undetectable after 14 days. The chronic stage of the disease (day 28 onwards) is characterized by mononuclear cell infiltration into the myocardium and the production of antibodies to cardiac myosin which, because of the absence of virus, argues for autoim- munity as the pathophysiological mechanism at this stage of disease. In vitro, cardiac myocytes can be infected and lysed by the virus and CVB infection causes myocardial destruction.
This damage may lead to autoimmunity via epitope spreading. In mice, virus-specific antibodies arise soon after infection, followed by antibodies to several cardiac proteins such as myosin, tropomyosin and actin.
While these studies show that numerous autoimmune mechanisms can lead to cardiomyopathy in infected mice, it remains uncertain if autoimmunity accounts for the pathology seen in humans.
Streptococcus pyogenes: group A strepcococcus
Infection with S. pyogenes can lead to inflammation of the heart, and the involvement of lymphocytes in cardiac pathology has been suggested for some time.
Studies have shown that bacterial materials and DNA can persist in host tissue for some years after infection, so it is possible that ongoing immunity against the bacteria may lead to bystander damage to the organ. However, it is accepted most predominantly that the autoimmune reaction is caused by molecular mimicry. Myosin has been identified as the dominant autoantigen in the heart, and myosin-reactive mAb derived from patients with acute rheumatic fever were shown be cross-reactive to both M protein (the major virulence factor of group A streptococci) and the streptococcus carbohydrate epitope N-acetylglucosamine.
Although somewhat controversial , infection with S. pyogenes has also been associated with the development of movement and behavioural disorders such as Sydenham chorea, Tourette’s syndrome and obsessive–compulsive disorder . Patients with these disorders often have antibodies to the basal ganglia in the brain, and molecular mimicry between basal ganglia and S. pyogenes-derived proteins remains the major postulated mechanism of disease induction. An early paper demonstrated antibody cross-reactivity between S. pyogenes membrane and neuronal cytoplasm in patients with Sydenham chorea .
Using serum, cerebrospinal fluid (CSF) and mAb derived from Sydenham chorea patients, dual-specific antibodies were found that react with both the immune-dominant carbohydrate epitope on S. pyogenes cell wall (GlcNAc) and with lysoganglioside GM1 on the surface of neurones. The same group demonstrated that GlcNAc-reactive antibodies from the sera of patients with pediatric autoimmune neuropsychiatric disorders associated with streptococci was inhibited by lysoganglioside GM1, and that lysoganglio- side GM1-reactive mAb from Sydenham chorea patients could also react with intracellular brain protein beta-tubulin.
Chagas disease is caused by infection with the protozoan parasite T. cruzi. 10–30% of infected individuals develop the disease, which occurs in two major clinical phases, acute and chronic. The acute phase is characterized by parasitaemia, preferentially in heart muscle cells, and inflammatory infiltration of infected tissue. This is followed by an asymptomatic indeterminant phase, which can last up to 30 years. Patients who progress to the chronic phase of the disease are affected mainly by irreversible cardiomyopathy.Although it has been suggested that parasite persistence can contribute to chronic Chagas disease cardiomyopathy (CCC), T. cruzi antigens and DNA can also be detected in infected people who remain asymptomatic. This suggests that the tissue destruction that characterizes this phase may be largely autoimmune. CCC is characterized histopathologically by mononuclear cell infiltrates, with CD8+ T cells outnumbering CD4+ T cells 2:1. Local production of interferon (IFN)-g, TNF-a, IL-4 and IL-6 has been reported. In addition, real-time polymerase chain reaction (PCR) analysis showed selective up-regulation of IFN-g-inducible chemokines and chemokine receptors in CCC heart tissue. Collectively, these data suggest that bystander tissue destruction mediated by inflammatory cytokines (especially IFN-g) may play a role in CCC pathology. Although the chronic phase usually affects the heart, a subset of patients develop motor dysfunction of the gastrointestinal tract, essentially through the destruction of neurones of the enteric nervous system. It was discovered that antibodies raised in rabbit against a flagellum- associated surface protein on T. cruzi (FL-160) are cross- reactive with a 48-kDa protein found exclusively in nervous tissue . It was then found that antibodies raised against the amino terminus of FL-160 react to a different epitope on mammalian sciatic nerve than antibodies raised against the carboxyl terminus. The medical relevance of this apparent mimicry is uncertain, as the ability of human sera to react to FL-160 did not correlate with clinical disease. Other studies have also shown molecular similarity between T. cruzi antigens and antigens from mammalian nervous tissue.
In the United States, Lyme disease is caused by the tick-borne spirochete Borrelia burgdorfeii (Bb). Sixty per cent of untreated patients develop arthritis that can last for several years, mainly in large joints such as the knee. These patients have high titres of Bb-specific antibodies, and Bb DNA can be detected in the joint fluid by PCR. Treat- ment of these patients with antibiotics usually ameliorates the arthritis, which indicates that bystander inflammatory response to the spirochete is responsible for early Lyme arthritis. A subset of patients will progress from acute to chronic arthritis despite treatment with antibiotics and lack of detectable Bb DNA in synovial fluid. Antibiotic- resistant Lyme arthritis is associated with the MHC class II alleles human leucocyte antigen (HLA)-DRB1*0401, *0101 and *0404, indicating that its mechanism is T cell-mediated and distinct from acute Lyme arthritis. Cellular and humoral responses to outer surface protein A (OspA) of Bb develop in around 70% of patients with antibiotic-resistant Lyme arthritis, often at the beginning of prolonged arthritic episodes. T cell and humoral responses to OspA, but not to other spirochete antigens, were found to correlate with the presence or severity of arthritis. Synovial fluid mono- nuclear cells from patients with antibiotic-resistant arthritis produced IFN-g in response to both OspA and LFA1a, suggesting that mimicry between these two proteins may cause the inflammation associated with arthritis. LFA-1a has also been identified in the synovia of patients with antibiotic-resistant Lyme arthritis.
Neurological complications, including myelitis and peripheral neuropathy, can occur in 10–12% of untreated patients infected with Bb and can arise even after antibiotic treatment. Patients with chronic neuroborreliosis have been reported to have antibodies reactive to nerve axons in their serum, as well as antibodies and T cells specific for myelin basic protein (MBP) in spinal fluid. Patient serum that was reactive to axons and neuroblastoma cells was also cross-reactive with Bb flagellin.
Next, it was discovered that a mAb for flagellin was cross-reactive with human heat shock protein 60 and with neuroblastoma cell lines and slowed neurite outgrowth in culture. Antibody cross- reactivity has also been described between human central nervous system (CNS) proteins and Bb OspA.
Herpes simplex virus
Herpetic stromal keratitis (HSK) is caused by corneal infection by herpes simplex virus (HSV) and can lead to blindness. Whereas progression from epithelial infection to stromal keratitis is not prevented by antiviral drugs, the symptoms of HSK can be alleviated with immunosuppressive drugs such as corticosteroids, indicating that HSK is an autoimmune disease. Because of the difficulties associated with studying the disease in humans, much of the characterization of HSK has utilized murine infection with HSV-1. Within 72 h of infection proinflammatory cytokines IL-1 and IL-6 are produced, which leads to influx of neutrophils into the corneal stroma. In humans, T cells may cause pathology via bystander destruction.
Uveitis is a group of intra-ocular inflammatory diseases that are potentially blinding.
It is believed that many sub- groups of this disease are autoimmune-mediated, in part because of the strong association with certain HLA alleles. Humoral and cellular responses to the retinal antigens interphotoreceptor retinoid binding protein and S-antigen are well characterized in humans and animal models in rodents and primates (experimental autoimmune uveitis, EAU) are based on injecting these proteins in complete Freund’s adjuvant. Singh et al. identified a CD4+ T cell epitope in human S-antigen and several virus and Escherichia coli-derived peptides with sequence similarity rotavirus and bovine milk casein . In the same study, patients with uveitis were found to have an increased T cell and antibody response to S-antigen and the two identified mimics compared with healthy donors. Aside for a report of an outbreak of uveitis in children after echovirus infection, no pathogen has yet to be associated epidemiologically with uveitis.
Type I diabetes (T1D) results from autoimmune destruction of pancreatic cells by autoreactive T cells and/or inflammatory cytokines. Although there is a definite genetic component to T1D, the concordance rate in monozygotic twins is only approximately 40%, and epidemiological evidence suggests that pathogens play a role in development. Many different viruses have been associated with T1D development. Studies showed a higher incidence of T1D in people with congenital rubella and antibodies to pancreatic islet cells in rubella- infected patients. Similarly, Cytomegalovirus (CMV) was isolated from T1D patients and antibodies to pancreatic islet cells detected in CMV-infected patients. It was also noted that mumps infection often preceded the onset of T1D in children. A convincing study showed that Coxsackievirus (CVB4) isolated from the pancreas of acute-onset patients could induce diabetes upon transfer into susceptible mice. CVB4-specific IgM antibodies could be detected in children newly diagnosed with T1D. There is some evidence that CVB4 may cause T1D via molecular mimicry. T cells isolated from T1D patients reacted with both glutamic acid decarboxylase (GAD-65) (an identified autoantigen in T1D) and protein 2C in CVB4. However, another study did not observe similar T cell cross-reactivity, and yet another showed that cross-reactivity was observed in both diseased patients and healthy controls. As the virus has also been shown to replicate in exocrine pancreas, it is possible that cytokine release and HLA up-regulation following mumps virus infection may lead to autoimmunity.
Guillain–Barré syndrome (GBS) is a paralytic illness affecting both myelin and axons of the peripheral nervous system. Several studies have demonstrated anti-glycolipid antibodies in the serum of a proportion of patients .There are different clinical variants of the disease, which can correlate with the specific type of glycolipid targeted by the antibodies. Glycolipids found most commonly in neural tissues include the Gangliosides and Cerebrosides. Onset of GBS occurs days or weeks following an infection or immu- nization. Although several microorganisms have been associated with GBS development, Campylobacter jejuni is the most extensively studied pathogen as it is a common antecedent to GBS. In addition, there is mounting evidence suggesting that lipopolysaccharide (LPS) on the outer core of the bacteria can mimic host gangliosides. LPS from C. jejuni serotypes associated with GBS were shown to resemble human Several studies have shown that C. jejuni serotypes associated with GBS are more likely to contain ganglioside-like epitopes compared with serotypes isolated from C. jejuni-infected patients with gastroenteritis but no neurological symptoms, with one study linking ganglioside mimicry to specific GBS clinical subtypes.Patients infected with Mycoplasma pneumoniae prior to the development of GBS often have antibodies to galactocerebroside. These antibodies can cross-react with glycolipids on M. pneumoniae Associated antibodies to GM1 have also been reported. Similar to what occurs following C. jejuni infection, patients infected with Haemophilus influenzae can develop antibodies to bacterial LPS that are cross-reactive with ganglioside. The presence of a ganglioside-like structure on the surface of H. influenzae suggests that molecular mimicry may explain its association with GBS induction.
Multiple sclerosis (MS) is characterized by a loss of the myelin sheath surrounding axons in the CNS. Demyelination is associated with elevated levels of CD4+ T cells specific for major myelin proteins, and the disease is generally thought to be autoimmune. Although it is not known precisely what triggers the development of MS, it is well established that relapses or disease flares in patients diagnosed with the relapsing–remitting form of MS are often associated with exogenous infections, particular upper respiratory infections. In total, more than 24 viral agents have been linked to MS. Most of the associations have been circumstantial, but some studies have found evidence of specific pathogens in human tissue. Antigens from herpesvirus type 6 were found in MS plaques but not from tissues from other neurological disorders. Similarly, compared with CSF from patients with other neurological diseases, CSF from MS patients was shown to have higher levels of the bacteria Chlamydia pneumoniae. In vitro studies have also provided evidence linking MS and infectious agents. Despite the difficulty in linking MS to any one pathogen, the amount of epidemiological evidence reported over the years shows that environmental factors play a strong role in disease development, and suggests that a cumulative lifetime exposure to certain microorganisms can influence disease development. In addition, a recent study showed that the degree of concordance for monozygotic twins (generally reported at 40% or less) was influenced by environmental factors.
The immune system has evolved checks and balances to prevent the destruction of host tissue. It is perhaps not surprising that a strong immune response to an invading pathogen could disrupt this regulation and lead to autoimmunity. There is significant evidence suggesting that different classes of pathogens (bacteria, viruses and parasites) are involved in triggering or propagating self- reactive immune responses. However, the evidence for a definitive link for infection-induced autoimmunity is stronger for certain diseases than for others.
The argument for infection-induced pathology is much stronger for diseases associated with one or two specific pathogens than for diseases with multiple causal associations. For example, the fact that infection with C. jejuni is a common antecedent to GBS makes a strong argument that this disease is infection-triggered. In contrast, for diseases such as TID and MS that have been associated with dozens of pathogens, but none in particular, much more needs to be done to make a convincing case. The most compelling proof
would be the disappearance of symptoms with the clearance of the infection. This is the case in Lyme disease, where treatment with antibiotics alleviates acute arthritis. There are many ways a pathogen can cause disease even after the infection has been cleared. In these cases, epidemiological studies showing that people infected with a particular agent have an increased incidence of these diseases compared with people never infected, while not wholly definitive, would certainly strengthen the infection-induced autoimmunity argument.
In human autoimmune diseases, where direct evidence for a role for a particular pathogen is still uncertain, it is all the more important to have supporting animal models. The strongest support comes from animal models in which infection with the agent thought to induce disease in humans causes similar symptoms in animals, as exemplified by induction of heart disease in mice infected with T. cruzi and CVB and arthritis in mice infected with Bb. In other animal models, disease can be shown to be induced by priming with a pathogen-derived antigen, thus strengthening the argument for the involvement of that pathogen in the human disease. The ability to induce heart disease in rats primed with Streptococcal M protein is strong evidence that S. pyogenes causes heart disease in humans via molecular mimicry. Although the link between S. pyogenes infection and neurological disorders in humans is uncertain, at best, the fact that movement and behaviour disorders can be induced in mice primed with S. pyogenes homogenate also lends credibility to that theory. In cases where it is uncertain whether a disease pathology is actually autoimmune (such as uveitis and myocarditis following CVB infection), animal models have played a crucial role in elucidating the potential mechanisms of disease induction.
The heterogeneity of the human population, rather than the weakness of the data, may be in play in instances where the evidence linking infection and autoimmunity is tenuous or even conflicting. It is not difficult to imagine that some people may be more susceptible to developing autoimmune disease following a particular infection than others, or that mimic peptides derived from different infectious agents may be able to trigger a particular autoimmune disease depending on the ability of the infected individual to present various epitopes in the context of their various HLA molecules. Defining the genetic markers that predispose patients to different autoimmune diseases with a suspected infectious trigger would be an important contribution to defining the underlying disease pathogenesis.
“Demystifying Pleomorphic Forms in Persistence and Expression of Disease: Are They Bacteria, and Is Peptidoglycan the Solution?”
Review by Jon Trister MD
The interaction of microbes within the host can lead to the enhancement or depression of their individual properties. Clinical expression of their presence in the host depends on the genetic vulnerability of the host, the particular environmental stresses, and the number and location of such consortia. The clinician who faces this tangled scenario must quantitate and define the dynamic that has led to the patient’s illness.
Many bacteria-like elements can be visualized at the ultra-structural level, but cannot be grown in culture. Nucleic acid analyses in vitro can approximate the locations of these bacteria on the phylogenetic tree. Unfortunately, none of these sophisticated laboratory procedures are consistently successful in identifying pleomorphic organisms persisting in tissues, nor are they guides to optimal therapy.
Pleomorphic, cryptic organisms, whether intra- or extracellular, are ubiquitous. A first step would be to demonstrate their presence in tissue samples when laboratories report culture negative findings in patients suspected of having a bacterial infection; or to attempt to grow them in culture. Quantifying and identifying the cells most parasitized are impractical routine clinical approaches. Koch’s postulates cannot be fulfilled, because it is impossible to precisely duplicate all the variables that are involved in disease expression.
Any patient with a history of recurrent infections and persistent disability is sending signals that this phenomenon is occurring. The autoimmune disorders, in which no organisms can be identified by routine techniques, are suspect in this regard. The selection of antimicrobial agents for patients with cryptic infections can be quite frustrating. Even if an organism grows in vitro, it may not represent the primary pathogen. In addition, drug susceptibility testing fails to reveal the action of the agent on the infecting organism’s toxicity and capacity to adhere to cell membranes in vivo.
Although physicians are discouraged from the indiscriminate use of antimicrobial agents without strong cultural, immunologic, or molecular evidence that the therapy is appropriate and that the severity of the illness justifies the risk of side effects, it is, nevertheless, a common clinical practice and undoubtedly contributes to the development of pleomorphic, persisting bacterial forms and mutants in vivo.
Survival of a species requires that a reasonable identity be maintained. Over time, mechanisms to maintain “self” have evolved. Many such relationships have been so successful that both host and invading organism benefit. Such a process, which transiently reduces immune competence, can occur episodically in healthy subjects in association with various stresses .
As one ages, there tends to be an insidious accumulation of intracellular microbial forms. Such quiescent organisms tend to be activated to a more toxic form when homeostatic disturbances threaten their cellular loci. The numbers and locations of cells involved with one or more types of organisms determine the clinical reaction. It can be very difficult to decide whether a new illness is due to a new organism or to an interaction with one or more pleomorphic cryptic organisms. These interactions can be as complex as the well-known increase in toxicity of Corynebacterium diphtheriae when this bacterium is infected by bacteriophage. The distinction between phage genes and bacterial genes is blurred with respect to both function and reality. It is conceivable that much of the heredity of bacteria is of viral origin, because many unknown defective proviruses may exist in nature; on the other hand, phages may be fragments of bacterial DNA that have acquired the capacity for independent reproduction. Indeed, with a history of mutual interaction of viruses and bacteria over the course of evolution, the endeavor of sharply distinguishing their genes must be meaningless. These philosophic concepts are implicit in any discussion of the role of dormant, persistent, difficult-to-culture, and impossible-to-culture bacteria in disease (Domingue and Woody, 1997).
From the evidence available in the literature, it seems that mycoplasmas are a diverse group of wall-less prokaryotes derived from various bacteria. It has been convincingly demonstrated by immunologic methodology that acholeplasmas are descended from streptococci, specifically from groups N and D. It therefore seems logical to conclude from molecular and immunologic data that mycoplasmas are not a true phylogenetic class and that they are not descended from one single common ancestor. A teleologic approach to the evolutionary relationship between mycoplasmas and cell wall-defective/deficient bacteria should consider the survival advantage of an organism with a cell wall in a hostile primordial environment. Only after the appearance of higher life forms was there a protective niche for mutant microorganisms (Domingue and Woody, 1997).
If we are to extend these findings to clinical relevance, it is tempting to speculate that in vivo genetic events may lead to development of bacteria with aberrant cell wall morphology and physiology and may involve complex interactions among a variety of bacteria and host cells. Such interactions might lead to persistence of a dormant bacterial phase in patients with infectious diseases. This may be a continual biologic process in all living hosts, with the host environment serving as the determinant for evolution, persistence, and survival of morphologically altered microbes. Previously described, newly published, provocative, molecular microbiological data lend credence to the hypothesis and corroborate the multiplicity of pleomorphic forms that develop during reproduction of L-forms in vitro. Recent studies on modifications of gene expression and modes of division for stressed bacteria are highly relevant to the hypothesis. It is proposed that in vivo persistence of these bacterial elements escape immune surveillance partially, completely, or may integrate with host cell organelles to create bacteria-host-cell-antigen complexes which could provoke immunopathologic consequences. To speculate further, bacterial persisters in a scenario of molecular mimicry might possess peptide sequence similarities with self peptides sufficient to result in cross-activation of autoreactive T or B cells by pleomorphic form derived peptides.
Might there also be an analogous situation to that of H. pylori growth in the human stomach: Do persistent atypical bacterial forms produce enzymes which neutralize hostile host factors creating a more hospitable tissue environment; and are there microbial factors antagonistic to white blood cells preventing their migration to the infectious site or scene of pleomorphic form persistence? Furthermore, there may be an exchange of genetic material between the persisting prokaryote nucleoid (oncogenic plasmids or unknown nuclear interactions) and host eukaryotic chromosome creating cellular alterations adequate to initiate neoplastic growths.
Scientists skilled in disciplines such as cellular adhesion, transposition of genetic elements, and microbial reassembly as mechanisms for the genesis of unusual organisms should be able to design, execute, and interpret experimentation that will confirm or refute, unambiguously, the proposed hypothesis. If pleomorphic forms in tissues are confirmed as bacteria by sensitive and specific methodology, the clinical and research implications are unlimited; and have the potential for clarifying the mysterious and poorly understood host-pathogen interactions in persistent infections and expression of innumerable idiopathic diseases.
The common pathogenesis of Alzheimer’s disease and diabetes.
By Renata Trister DO
Recent studies show new evidence that Alzheimer’s disease and type 2 diabetes share common features in their pathophysiology. Insulin resistance is a characteristic feature of both diseases. Glucose metabolic disorders, related to Alzheimer’s disease, are type 2 diabetes, and pre-diabetes/metabolic syndrome. Based on the common pathophysiology of these two diseases, Alzheimer’s disease is by some called type 3 diabetes. This is yet another example of chronic illnesses that caused by modern diets and lifestyle habits. Diets high in refined carbohydrates lack of sleep and physical activity all contribute to insulin resistance. In the research on dementias, insulin resistance has much documented harmful effects on cognitive function. Insulin-like growth factor also influences cognitive functions. Insulin resistance causes glycation and oxidative stress on the brain. In Alzheimer’s brains, amyloid deposition, hyper-phosphorylation of tau proteins and neurofibrillary tangles, are characteristic features. Amyloid ß is co-secreted in the ß-cells of the pancreas with insulin. Amyloid ß and hyper-phosphorylated tau protein can be found in the Langerhans islets (in autopsy). Amyloid deposits, found in the pancreas and brain are similar. As a result of hyperglycemia, glycation end products cause the development of amyloid plaques, neurofibrillary tangles; these are all typical in Alzheimer’s disease. Hyperglycemia leads to oxidative stress, which plays significant role in the development of both illnesses. Low-grade inflammation is also a significant pathophysiological factor in both disorders. The sources of this inflammation are inflammatory adipo-cytokines, dysbiosis, and metabolic endotoxemia, caused by lipopolysaccharides. Cerebral glucose metabolism is also impaired in Alzheimer’s disease. A reduced presence of insulin and resulting decrease in cerebral glucose metabolism creates an energy crisis in the brain. Neurons are unable to harvest energy and basically starve. In order to conserve energy, these affected neurons degrade axons and dendrites. The retraction of these projections results in damaged synapses and cell communication loss. Symptomatically, this presents as cognitive impairment. Another possible etiology of this glucose deficit is reactive hypoglycemia. Reactive hypoglycemia is low blood glucose that occurs within four hours after eating, especially high glycemic foods. After eating sugary foods, blood glucose levels spike rapidly and become very high. In response insulin is produced. Reactive hypoglycemia results from having too much insulin produced in response to eating, leading to low blood glucose levels. This happens chronically and can be very damaging. During waking hours the symptoms are quickly ameliorated by having another snack. However, consuming sweets at night, this hypoglycemia goes unnoticed and not corrected. This hypoglycemic state continues until you wake up and eat. Consequently cells in the body have an energy deficit. Alzheimer’s disease is a heterogeneous disorder, and as yet there is no effective therapy. Encouraging results have emerged by using intranasal insulin spray. Insulin sensitizers like metformin, have shown some improvements in cognitive functions, mainly in animal experiments. The real breakthrough comes from prevention of both chronic diseases via a healthier life-style. Reducing refined carbohydrates in diet appears essential.
In 1928, Albert Szent-Gyorgyi discovered Vitamin C> He won Nobel Prize in 1937 for its discovery.
Man , monkey are unable to synthesize vitamin C which make them dependable on exogenous sources.
Vitamin C is NOT an Ascorbic Acid. Ascorbic acid is a PART of Vitamin C Complex which also, in addition , includes Vitamin P complex ( bioflavonoids).
Through recorded history, Scurvy was the scourge of armies, explorers, and sailors on extended trips without fresh food, until they learned to include an adequate source of vitamin C, such as lime juice, in their diet.
Function of Vitamin C:
2.Degradation of protein to amino acids
3.Synthesis of neurotransmitters.
4.Most active reducing agent
Collagen is the most abundant structural protein in the body tissues. Collagen is a foundation of structural integrity of all organs.Collagen ( and vitamin C) is essential for the deposition of the calcium phosphate crystals to form mature bone.Vitamin C provides the collagen needed for elastic vessel wall and required for synthesis of the essential neurotransmitters-epinephrine and serotonin.Vitamin C is important for detoxification, stress response,reduces susceptibility to infections.
Vitamin C is needed for the hydroxylation of the amino acids lysine and proline to proto-collagen molecule.
Initially, scorbutic patients presents with weakness, lassitude, irritability, and vague aching pains in the joints and muscles.They may complain of weight loss. Later, as the disease progresses easy bruising and even hematoma in the skin and muscles develop.
The gums become swollen, red and bleed easily.
Perifollicular hyperkeratotic papule develop.
Deficiency in the USA due to inadequate dietary intake, smoking, alcoholism, intestinal dysfunction and in patients with psychiatric illnesses.
Vitamin C is present in fresh fruits and vegetables, and especially deep green buckwheat juice.This juice contains high quality of Vitamins C, P and Rutin.
ANTI CANDIDA DIET
By Renata Trister DO
Most of the anti Candida diets recommend removing sugar, starch, alcohol, and refined foods–candida’s preferred food sources. However, cutting all starchy carbs with a very low carb diet may not be the optimal plan, and studies indicate that yeast may actually feed on the ketones that result from a very low carb diet. So cutting all starches and sources of glucose isn’t a great idea. The best diet will depend mostly on you. We each have a gut microbiome as unique as our fingerprint. If you have leaky gut, intestinal inflammation, or malabsorption issues, you may fare well on the specific carbohydrate diet or low FODMAP diet that limits hard-to-break -down starches (see links below for more information). When a compromised digestive tract can’t fully break down these complex starches (grains, potatoes, certain legumes), they ferment, feed yeast, and cause gas and bloating.
There is a 3-part process used to kill candida overgrowth. It involves starving the candida, killing it and reinoculating the gut with good bacteria. Note that you may need to complete this cleanse more than once to completely get rid of it. Plan on 8 weeks.
Eliminate gluten, dairy, refined white sugar, soy, processed foods, corn, and ideally grains (gluten free grains can be excepted) Focus on organic eggs and animal protein + vegetables and good fats. Note that diet alone will not kill the yeast overgrowth! You have to combine diet with herbal protocol.
• Consume high quality, hormone-free protein at each meal from sustainable, antibiotic-free sources: Wild, cold water fish; free-range chicken & turkey; properly prepared legumes (soaked); cage free eggs; beef/bison; lamb
• Eat plenty of fresh vegetables: lightly cooked, sautéed, steamed, and raw. Focus on leafy greens and cooked cruciferous
• Use good quality fats for cooking: olive oil, coconut oil, and ghee. Avoid vegetable oils!
• Drink filtered water (6 – 8 glasses/day to help flush toxins)
• Drink 2-3 cups of Pau d’arco herbal tea daily, and bone broth. Bone broth heals the gut and Pau d’Arco helps kill yeast.
• Add fermented foods such as raw kraut, kefir or kimchi (recipe video link below).
• Take 1-3 tbsp. of coconut oil daily. It’s a powerful yeast killer and boosts metabolism.
• Take 1 tsp. apple cider vinegar in a little water if needed to help digestion and detox. Avoid all other vinegars! Candida feeds on the sugars produced from this type of fermentation.
Foods to Avoid
Aged Cheeses & Dairy Products Conventional dairy contributes to inflammation, and many people are dairy sensitive. Raw dairy is ok occasionally if you’re not sensitive. Fermented dairy (kefir, preferably raw) is ok occasionally if not dairy sensitive, but dairy contributes to dampness in the body.
Additives & Preservatives Anything you can’t pronounce on a food label = trouble.
Conventional Meats & Eggs Use only grass-fed meat products, free-range eggs, and chickens. Non-organic animal proteins contain antibiotics and steroids that contribute to inflammation.
Alcohol Sugar in the alcohol (wine, beer, spirits) is a food source for candida
Over-use of coffee Coffee is acidic, depletes minerals and thins the gut lining. Use green teas and herbal teas.
Fruits The high sugar contents of fruits makes Candida thrive; so stay away from sweet fruits! (Exceptions are berries, lemons, limes low sugar fruits.) You may drink fresh green juice as long as the fruit content is minimal.
Gluten & Grains Avoid anything made from wheat, rye, and barley.
Peanuts Peanuts carry a mold called aflatoxin that contributes to toxins in the body.
Condiments and YEAST in any form Condiments (chutneys, mustards, preserves, ketchup, relishes, vinegar, bottled dressings, etc.) tend to be high in sugars, corn syrup and preservatives. Vinegars feed yeast.
Killing The Candida.
Along with the diet, you’ll need to take herbs to kill off excess candida. You can start the diet and the herbs at the same time. The main antifungal supplements are the following: caprylic acid, pau d’arco, berberine, grapefruit seed extract, zinc, biotin, olive leaf extract and oregano oil. Take the herbs three times daily for at least 6 weeks. If you’ve tried to get rid of candida before unsuccessfully, you may need to rotate between different anti-candida products. Candida builds up a fast resistance to herbs.
Try some stress relief during this phase: meditation, yoga classes, walking, gardening, whatever relaxes and rejuvenates you. You may also use aloe to soothe the gut lining if there is inflammation. A digestive enzyme (Zypan or DiGest from Standard Process are good options) will help you break down food and excess toxins as the candida dies off. Drinking aloe juice is soothing to the gut and helps kill candida.
Warning: some will feel worse before they feel better. People report feeling achy, flu-like symptoms. This could be a reaction to the yeast dying off, which overwhelms detox pathways. This is called a Herxheimer reaction. Liver support tonics and activated charcoal can be used to help rid the body of toxins.
Reinoculate the gut with good bacteria and starve the remaining candida. This is done with a good quality probiotic along with naturally fermented foods.
Books and links on diets Body Ecology, GAPs & FODMAPS:
KIMCHI recipe video link:
http://www.maangchi.com/recipe/easy-kimchi There is another white kimchi recipe on same site that is very good with easy to find ingredients.
Toxic Skincare and Beauty Products
Renata Trister DO
The skin absorbs about 60% of what we put on it and what is applied to the skin might be an even greater risk for toxin exposure than what you put in your mouth. When you eat, a vast system of digestion and excretion breaks down what’s ingested and flushes it out of the body. However, chemicals on the skin are absorbed into the bloodstream without such filtering.
The average woman uses 12 different personal care products contain 170 different ingredients everyday. An astounding number of personal skincare ingredients are linked to cancers, allergies, neurological disorders and reproductive issues. Understanding labels and finding alternatives is important. This article will discuss some of the most toxic ingredients to avoid and provide some alternatives.
Triclosan is an antimicrobial agent found in hand sanitizer, but is also added to soap, shampoo, and even tissues! It can be absorbed through the skin, and has been detected in human urine, serum, and breast milk. Triclosan hand sanitizer is probably THE MOST important ingredient to avoid. Hand washing with plain soap is healthier for you and everything around you.
Recent focus on the importance of our micro biome and the growing threat of drug resistant bacteria, the widespread use of unnecessary antibacterial agents has come under question. Studies as early as 2006 have expressed concern over bacterial resistance to triclosan, as well as the greater fear of triclosan-induced resistance to clinically important antimicrobial drugs. Just think of it this way by killing the 99.9% of bacteria (as some bottles claim) the resistant .1% get a greater chance to survive & multiply.
A study was released linking triclosan exposure to liver cancer in mice. In the study, triclosan acted as a cancer promoter, meaning it increased susceptibility to cancer and accelerated tumor formation after long-term exposure.
Triclosan has also been suspected as an endocrine disruptor, although a recent review of the literature concludes that triclosan exposure through the use of personal care products is unlikely to adversely affect endocrine function in humans (although this review was funded by the Colgate-Palmolive Company) and although there’s limited or no evidence that triclosan exposure through personal care products has harmful effects in humans, several studies have shown triclosan to adversely affect thyroid and reproductive function in rats.
Finally, triclosan antibacterial soaps do not provide any benefit over regular soap for preventing the spread of disease! There is no reason to use this and triclosan should be avoided all together.
Phthalates and Parabens
Phthalates and parabens are found in a variety of personal care products, although phthalates are more common in lotions because they act as moisturizers and enhance skin penetration of other compounds. Parabens are absorbed through the skin intact. Both chemicals have been detected in breast milk, urine, and plasma.
Phthalates and parabens increase the risk for breast cancer. An increased concentration of phthalate metabolites in the urine was associated with an increased risk for breast cancer, and intact parabens have been detected in breast cancer tissue. Phthalates have also been implicated in reproductive and endocrine disruption, although like triclosan, the evidence is preliminary.
Sulfates and Fragrances
Sulfates, such as sodium laurel sulfate and sodium laureth sulfate, fragrances, and petroleum by-products are some of the other chemicals commonly used.
Sodium lauryl sulfate, SLS is a detergent and a surfactant (it breaks surface tension and separates molecules in order to allow better interaction between the product and your hair and skin). This in turn creates a lather which makes products such as shampoo and toothpaste more effective cleaners. Sodium Lauryl Sulfate is found in a number of industrial cleaning agents such as engine degreaser. SLS is also widely used as a skin irritant when testing products used to heal skin conditions.
The term “fragrance” is vast, they’re a common cause of contact dermatitis. Fragrances are poorly regulated, and “fragrance” on an ingredient label could mean just about anything. Many dangerous ingredients can be manipulated and categorized as a fragrance. Initially, perfume companies fought the law to list their ingredients so that the secret recipes are not stolen. Thus the term fragrance was born. Now, however dangerous chemical can be classified as a fragrance to avoid getting listed as an ingredient.
There are many safe soap options. Just look for soap that only contains oils and other recognizable ingredients.
Oils like coconut, jojoba, and even olive oil are great for your skin and widely available.
Shampoo can be a little harder to eliminate. There is an adjustment period. Simple ingredients such as bentonite clay, apple cider vinegar, and honey can clean and condition hair.
A simple 1-time use shampoo can be made with raw honey! (1tablespoon RAW honey with 3 tablespoons water. You may add 2 drops of carrot seed oil and 2 drops of essential oil such as Rosemary or lavender – the oils are optional). Many online resources are available; this is a good example – http://thehealthyhoneys.com/natural-hair-care/.
Another option would be to forgo soap and shampoo entirely. This might sound extreme research has shown that like our gut, the skin has a micro biome. This micro biome acts as a built-in cleanser, deodorant, anti-inflammatory and immune-booster. The chemicals in skin care can disrupt this micro biome.
In fact, new companies now offer a product that contains Nitrosomonas eutropha, an ammonia-oxidizing bacteria (AOB). AOBs are commonly found in soil and are the reason why animals take “dirt baths” by rolling in the soil. These bacteria were once commonly found on our skin but are easily washed away with soap and shampoo. AOBs, convert the urea and ammonia in sweat—which is abrasive to the skin, causing acne and irritation—into nitrite, which fights most bad bacteria, and nitric oxide, which has anti-inflammatory properties. The idea is that these bacteria will help restore our skin’s natural protective, moisturizing and cleansing abilities, thus reducing or eliminating the need for skin care products.
A growing number of people have chosen to eliminate soaps and shampoos. Although this may be a bit radical for some, check out this article in the New York Times for a good summary and explanations.
Cobalamin (vitamin B12) Deficiency
By Renata Trister DO
According to data obtained in the Tufts University Framingham Offspring Study suggests that nearly 40% of people (ages 25-83) have plasma B12 levels in the low normal range. 9% had a significant deficiency and 16% had a near deficiency. Even a mild vitamin B-12 deficiency is associated with a greater risk for accelerated cognitive decline.
B12 deficiency has been estimated to affect about 40% of people over 60 years of age. In these patients, some of the symptoms we attribute to “normal aging” such as cognitive decline and memory loss may in part be caused or exacerbated by B12 deficiency.
Vitamin B12 works together with folate in the synthesis of DNA and red blood cells. It’s also involved in the production of the myelin sheath around the nerves, and the conduction of nerve impulses.
Dietary sources and availability
Microorganisms such as bacteria and algae synthesize and are the source of vitamin B12. The vitamin made by these microorganisms enters the human food chain through incorporation into food of animal origin. In vegetarian/ruminating animals, gastrointestinal fermentation supports the growth of these vitamin B12-synthesising microorganisms. The vitamin is absorbed and incorporated into their tissues. Omnivores and carnivores derive dietary vitamin B12 from animal products (i.e., milk, cheese, eggs, meat).
The absorption of vitamin B12 in humans is complex. Vitamin B12 in food is bound to proteins. The hydrochloric acid present in the stomach cleaves B12 from these proteins. The free form of the vitamin is immediately bound to glycoproteins called R-binders /haptocorrins. This protects B12 from denaturation in the stomach. Intrinsic factor, secreted by parietal cells in the stomach, binds vitamin B12 and enables its active absorption. When the contents of the stomach enter the duodenum, the R-binders become partly digested by the pancreatic proteases, release vitamin B12. The pH in the duodenum is more neutral than that in the stomach, the intrinsic factor has a high binding affinity to vitamin B12, and it quickly binds the vitamin as. The vitamin B12-intrinsic factor complex then proceeds to the lower end of the small intestine, where it is absorbed by phagocytosis by specific ileal receptors.
Over the last 10 years several definitions of Cobalamin deficiency have been published. Cobalamin metabolism is complex and involves a series of processes. A dysfunction in any of these processes can result in a deficiency. The main causes of Cobalamin deficiency are food-cobalamin malabsorption (50%), pernicious anemia (30%), insufficient nutritional vitamin B12 intake (7%) and malabsorption (5%). Dietary causes of the deficiency are found in malnourished elderly people and in strict vegetarians while malabsorption occurs in patients suffering from several gastrointestinal conditions.
Vitamin B12 is an important co-enzyme required for the production of tetra-hydrofolate, which is necessary for proper DNA synthesis. B12 deficiency results in impaired DNA formation and consequent retardation of cell division. This process results in the formation of megaloblastic cells especially in tissues with rapid turnover such as hematopoietic cells and intestinal epithelial cells.
Although measurement of vitamin B12 levels is the gold standard for the diagnosis of B12 deficiency some reports do exist concerning difficulties in its assay. The availability of vitamin B12 depends on its absorption from the ileum and its transport in blood to the liver and bone marrow by a carrier protein called transcobalamin. Circulating vitamin B12 is bound to 2 proteins, haptocorrin and transcobalamin.
Many case reports of normal plasma cobalamin levels in patients with clinical signs of vitamin B12 deficiency and a response to treatment with the vitamin.
B12 deficiency is often missed for two reasons. First, it’s not routinely tested for. Second, the low end of the laboratory reference range may be too low. Many B12 deficient people have so-called “normal” levels of B12.
Severe B12 deficiency – pernicious anemia (an autoimmune condition where the body destroys intrinsic factor, a protein for the absorption of B12). Anemia is the final stage of B12 deficiency. Long before anemia, B12 deficiency causes several other problems, including fatigue, lethargy, weakness, memory loss and neurological and psychiatric problems.
Causes of B12 malabsorption include:
• Intestinal dysbiosis
• Leaky gut and/or gut inflammation
• Atrophic gastritis or hypochlorhydria (low stomach acid)
• Pernicious anemia
• Medications (PPIs and other acid-suppressing drugs)
In general, the following patients are at risk for B12 deficiency:
• Vegetarians and vegans
• Aged 60 or over
• Regularly use PPIs
• Crohn’s disease, ulcerative colitis, celiac or IBS
B12 is the only vitamin that contains a trace element (cobalt), which is why it’s called coalmine.
Treatment of B12 deficiency
Cyanaocobalamin is the most frequently used form of B12 supplementation in the US. But recent evidence suggests that methylcobalamin is superior to cyanocobalamin especially in neurologic and psychiatric illness. Methylcobalamin is better absorbed because it bypasses several potential problems in the B12 absorption cycle. In conclusion, if the diagnosis of B12 deficiency is suspected on the basis of clinical findings, supplementation treatment should be administered even if the assayed level of the vitamin is not low.
Dr. Renata Trister DO
History of vitamin D
Vitamin D was categorized as a vitamin when it was discovered in 1922. It is not a true vitamin because an ongoing nutrient source is not required to sustain normal levels in the body. Vitamin D is properly classified as a secosteroid (derived from steroid) hormone precursor. A hormone is a chemical substance produced by one organ and then transported in the bloodstream to a target organ, where it causes a specific biological action.
Vitamin D has several metabolites (forms). This summary is limited to two metabolites: 25-D and 1,25-D.
25-D (also known as calciferol, 25-hydroxycholecalciferol) increases calcium absorption in the gut and at high levels, acts as an antagonist on the Vitamin D Receptor. 25-D is produced in the liver and synthesized in the cells of the skin in reaction to sunlight. 25-D dietary sources (fish, fish oils, eggs), foods that are supplemented with vitamin D (dairy products, cereals.) and vitamin supplements.
25-D is the major circulating form of vitamin D. It is used in the production of (1,25-D) in the kidneys.
1,25-D (also known as calcitriol or 1,25-dihydroxycholecalciferol or 1,25-dihydroxyvitamin-D3) is a potent secosteroid paracrine mediator and virtually affects all cellular activity.
1,25-D is primarily formed in the kidneys; but may also be formed skin, macrophages and other tissues.
Vitamin D dysregulation
The innate immune system refers to the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner. This means that the cells of the innate system recognize and respond to pathogens in a generic way, but unlike the adaptive immune system, it does not confer long-lasting or protective immunity to the host. The innate immune system provide immediate defense against infection.
Vitamin D is an important immune-modulator.
1,25-D can activate the innate immune system. Elevated levels can be found in patients with chronic conditions.
25-D can suppress the innate immune system.
Normally, production of 1,25-D is tightly controlled by the kidneys in response to a complex system of hormonal regulation. However, when nucleated cells are infected with bacterial pathogens, 1,25-D is generated by the inflammatory response. This causes the level of 1,25-D to exceed the upper limit normally controlled by the kidneys.
It is essential to measure both 25-D and 1,25-D to evaluate vitamin D levels and dysregulation. The level of 25-D doesn’t directly reflect the level of 1,25-D. Patients with Th1/Th17 inflammation often have a low level of 25-D while the level of 1,25-D is high. T helper 17 cells (Th17) are a subset of T helper cells producing interleukin 17 (IL-17) discovered in 2007. They are considered developmentally distinct from Th1 and Th2 cells and excessive amounts of the cell are thought to play a key role in autoimmune disease such as multiple sclerosis, psoriasis, autoimmune uveitis, juvenile diabetes, rheumatoid arthritis, and Crohn’s disease.
GASTROINTESTINAL HEALTH, THYROID and IMMUNE CONNECTION
By Renata Trister DO
“All disease begins in the gut.”
The health of your gut and the function of your thyroid are interrelated. Poor gut health can suppress thyroid function, and low thyroid function can lead to an inflamed and leaky gut.
Low Thyroid <—->Inflammation<—->Immune Dysregulation<—->Leaky Gut<—->Low Thyroid
The gut-thyroid-immune connection
About half the lymphocytes of the immune system are in the Mucosa-associated lymphoid tissue (MALT). MALT is situated along the surfaces of all mucosal tissues. The mucosa-associated lymphoid tissue initiates immune responses to specific antigens encountered along all mucosal surfaces. These surfaces protect the body from an enormous quantity and variety of antigens. MALT includes gut-associated lymphoid tissue (GALT), bronchial/tracheal-associated lymphoid tissue (BALT), nose-associated lymphoid tissue (NALT), and vulvovaginal-associated lymphoid tissue (VALT). The nomenclature is based on location. The gut contains a large portion of the body’s immune tissue. This portion of the immune system is referred to as GALT, or gut-associated lymphoid tissue. Gut-associated lymphoid tissue is comprised of Peyer’s patches, inter-digitating lymphocytes, plasma cells and lymphocytes present in the lamina propria, and mesenteric lymph nodes. The role of GALT is to manage the immune response to the massive antigen exposure experienced by the gut while maintaining a potent adaptive immune response to protect the host from mucosal pathogens. The mucosal epithelium of the gastrointestinal tract is inundated by potential pathogens on a continuous basis. Salivary enzymes, gastric acidity and surface mucous production provide protection sufficient against numerous invaders. However, an adaptive immune response is necessary to fully protect organisms against all virulent microbes. In the gut, a network of interdigitating lymphocytes in the epithelium, in addition to lymphocytes and plasma cells that circulate through the lamina propria, play an important role in mounting the proper immune response against pathogens.
Problems occur when either of these protective functions of the gut are compromised. When the intestinal barrier becomes permeable (i.e. “leaky gut syndrome”), large / partially digested food particles escape into the bloodstream. Since these food particles don’t belong outside of the gut, the body mounts an immune response and attacks them. In fact, these food particles become a “pathogen” putting strain on the immune system.
Gastrointestinal manifestations of thyroid dysfunction are numerous and involve all portions of the tract. Thyroid hormone action on motility has been widely studied, but more complex pathophysiologic mechanisms are not fully understood. Both thyroid hormone excess and deficiency can have similar digestive manifestations, such as diarrhea, although the mechanism is different in each situation. The liver is the most affected organ in both hypo- and hyperthyroidism. Specific digestive diseases may be associated with autoimmune thyroid processes, such as Hashimoto’s thyroiditis and Grave’s disease.
Thyroid hormones influence tight junctions in the gut. These tight junctions are closely associated areas of two cells whose membranes join together to form the impermeable barrier of the gut. Thyroid hormones promote actin polymerization. Hypothyroid conditions could affect tight junction functionality as tight junction proteins are directly linked to the actinomyosin cytoskeleton. Conformational changes in the cytoskeleton of epithelial cells may result in alterations in the function of the tight junction, which leads to increased para-cellular permeability. As a result, luminal contents can more penetrate the lamina propria causing an immune and/or inflammatory reaction influence the tight junctions in the small intestine. T3 and T4 have been shown to protect gut mucosal lining from stress induced ulcer formation. Likewise, thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH) both influence the development of the GALT. T4 prevents over-expression of intestinal intraepithelial lymphocytes (IEL), which in turn causes inflammation in the gut.
Gut bacteria and the thyroid connection
Healthy gut bacteria assists in converting about 20 percent inactive T4 thyroid hormone into the active form of T3 by producing an enzyme called intestinal sulfatase. An imbalance between harmful and beneficial bacteria in the gut, called intestinal dysbiosis, significantly reduces the conversion of precursor thyroid hormones to active T3. This is one reason people with poor gut function may have thyroid symptoms but normal lab results. Inflammation in the gut also reduces T3 by raising cortisol. Furthermore, low stomach acid, increases intestinal permeability, inflammation and infection (see article acid reflux).
Constipation can impair hormone clearance and cause elevations in estrogen, which in turn raises thyroid-binding globulin (TBG) levels and decreases the amount of free thyroid hormones available to the body. On the other hand, low thyroid function slows transit time, causing constipation and increasing inflammation, infections and malabsorption.
Hypothyroidism impairs gallbladder function by reducing bile flow; a sluggish gallbladder interferes with proper liver detoxification.
Healing the intestine-thyroid axis
These connections make it clear that you can’t have a healthy gut without a healthy thyroid, and you can’t have a healthy thyroid without a healthy gut. To restore proper function of the gut, both must be addressed simultaneously.
The influence of thyroid hormones on the gut is immense. Low thyroid hormones make it difficult to heal the gut, while an inflamed and leaky gut contributes to many illnesses, including hypothyroidism.