Previous research has shown that biotin deficiency increases inflammation but since there are so many causes of inflammation – physiologically speaking – the actual metabolic pathways between biotin deficiency and inflammation are unclear. In this study, researchers subjected human immune cells to biotin deficiency and compared the result to human immune cells living in a biotin-rich environment. Biotin, also known as vitamin B7, is a key vitamin necessary for proper cellular metabolism. It is a cofactor to cellular energy production and therefore important to cellular health at a fundamental level.
When the human immune cells were biotin deficient, expression of inflammatory proteins increased. Specifically, CD4+T cells were used, which are also known as T-helper cells because they are a type of white blood cell that directs the function of other immune cells. In other words, T-helper cells supervise immune cells, sending signals to attack viruses and bacteria, for example. In biotin deficiency, the number of these regulatory immune cells (CD4+T) decreased. At the same time, biotin deficiency caused an increase in the metabolic pathway (called mTOR) that regulates cell growth. mTOR (mammalian target of rapamycin) is a protein that senses the nutrient and energy status of cells and regulates their metabolism accordingly. A decrease in mTOR is generally good and can lead to a longer lifespan. An increase in mTOR is generally bad and can lead to tumors or cancerous growths.
The results of this study – both in vivo and in vitro – showed that biotin deficiency increased the mTOR pathway, which then resulted in an increase in several inflammatory compounds. This, combined with the fact that biotin deficiency decreased the number of T-helper cells, meaning fewer immune cells were around to regulate everything, ultimately induced the increase in inflammation seen in biotin deficiency.
(Journal of Immunology, April 2018)
LINK to ABSTRACT Biotin Deficiency Induces Th1- and Th17-Mediated Proinflammatory Responses in Human CD4+ T Lymphocytes via Activation of the mTOR Signaling Pathway.
Huntington’s disease is a relatively rare disease that occurs when a person has altered expression of a specific gene called the huntingtin gene.The presence of this mutated gene initiates the synthesis of an altered protein(similarly called the mutated huntingtin protein, or mHTT) that damages nerve cells in the brain over time. The disease progresses over the course of several years and clinically manifests as gradually worsening mental, emotional and physical dysfunction, to the point of totalincapacity.
Inthisexperiment,scientistsstudiedtheeffectofsupplementalvitaminB1(thiamine)onBlymphocytes(white blood cells) that carried the mutated Huntington gene and compared them to normal B lymphocytes that did not carry the mutated gene, which served as the control. The scientists supplemented vitamin B1 on the two sets of cells and compared the following: (1) cell growth rates, (2) vitamin B1 intake into the cell, (3) genetic profile of 27 different thiamine related genes and (4) the enzyme activity of several B1-dependentproteins.
They found that supplemental vitamin B1 stimulated more of an increase in growth in the mutated Huntington gene cells than the control cells, suggesting the Huntington cells had a higher requirement for vitamin B1. In addition, vitamin B1 intake, and therefore intracellular levels, was increased in the Huntington cells compared to control. Enzyme activity did not differ between cell types, but the expression of genes related to B1-dependent energy metabolism did differ between the control and mutated cell groups.
VitaminB1isknownforitsroleinenergymetabolismanddeficiencyhasbeenlinkedtoaseveralneurological syndromes such as Alzheimer’s disease and Wernicke encephalopathy, which suggests it may play a role in Huntington’s disease. Although this study was done in vitro (in test tubes), the increased expression of B1-related genes upon supplementation of B1 suggests intracellular vitamin B1 levels may play an important role in the manifestation of this enigmaticdisease.
(Advances in Clinical and Experimental Medicine, August 2017) Role of thiamine in Huntington's disease pathogenesis: In vitro studies.
Epigenetics – the study of changes in organisms caused by modification of gene expression rather than alteration in the genetic code itself– has gained much attention in recent years. Environmental factors including diet, smoking and stress have been shown to impact gene expression through epigenetic mechanisms. In a recent experiment involving the collaboration of several medical institutions, an experiment was performed on mice to determine how their immunity responded to a typical Western diet. When mice were fed a Western diet, systemic inflammation occurred which was entirely expected. However, what was particularly interesting was that the Western (inflammatory) diet fundamentally changed their immune system. After eating high calorie, low nutrient food, not only did the mice exhibit more systemic inflammation (not surprising), but their white blood cells became programmed to remain hyper-sensitive to inflammatory triggers. The cellular “memory” had changed. Here is how it worked: a gene called NLRP3 (for Nucleotide binding domain Like Receptor Protein) makes a protein that is used by our immune cells to recognize harmful bacteria and viruses. This protein made by the NLRP3 gene recognizes “bad” cell remnants. These can be parts of bacterial cell membranes, or pieces of genetic material found in viruses, or even parts of a cell that are supposed to be contained but may leak out due to cellular trauma. It is a fundamental way our immune cells recognize something is wrong – bacteria are present or acute tissue damage occurred, for example – and thus launch an inflammatory response to deal with the biological crisis and take care of it. In this study, the immune cells in mice fed a typical Western diet of high-calorie, low nutrient foods launched the same inflammatory response as if an invading bacterial infection were present. Furthermore, the immune cells became hypersensitive so that they continued their inflammatory attack, even when the mice’s diet was returned to normal. In other words, the immune cells responded to a Western diet in the same way it responds to infections. But instead of the infection clearing up, the Western diet seemed to reprogram the immune cells to stay in a perpetual hyperactive state. These results may help explain why chronic inflammation is behind so many lifestyle-related diseases such as heart disease, obesity and diabetes.
LINK to ABSTRACT Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming.
In a group of 33 young adults with treatment-resistant depression, plasma, urine and cerebral spinal fluid were measured for several metabolites. These were compared to levels of 16 healthy control subjects. Folate deficiency in cerebral spinal fluid was the most common deficiency seen in patients with pharmacological treatment- resistant depression. It is worth noting that serum levels of folate were normal in these same patients. All patients with cerebral spinal folate deficiency showed improvement in depressive symptoms when treated with folinic acid, suggesting that serum measurement of folic acid may be misleading as it does not reflect a functional deficiency. In fact, when folic acid deficiency was confirmed (in this case via cerebral spinal fluid), an unexpectedly large proportion of patients with potentially treatable depression were identified.
The thyroid gland, located in the neck, produces a variety of thyroid hormones. These regulate virtually every aspect of metabolism: body temperature, mood, sex hormones, energy levels, and even impact one’s appearance, from hair and nails to skin and waistline. Less understood about thyroid hormones is that there are two basic types – T3 and T4 (so named for the number of iodine molecules each has) – and they serve different biological functions. T4, which is made in the thyroid gland, serves as the precursor hormone to T3. It is entirely possible, even common, for the thyroid gland to produce plenty of thyroid hormone in the form of T4, but not be converted into T3. Because T3 is the more biologically potent thyroid hormone and acts directly on bodily tissues, one may exhibit signs of hypothyroidism (fatigue, weight gain, feeling cold, thinning hair, mood swings, etc) even when T4 is in the normal range.
It is worth noting that the conversion of precursor thyroid hormone T4 into active thyroid hormone T3 occurs outside the thyroid gland, mostly in the liver and kidneys. This conversion into active thyroid hormone occurs through the action of enzymes that are dependent on the mineral selenium (these enzymes are called deiodinases because they remove aniodine in T4 to convert it to T3). Therefore, a selenium deficiency can cause a person to be low in active thyroid hormone, even if their thyroid gland is producing plenty of precursor thyroid hormone. To complicate things, TSH (thyroid stimulating hormone) is often found to be “normal” despite poor thyroid conversion. In essence, a reliance on simple thyroid tests may suggest a person is not hypothyroid when in fact they are hypothyroid due to a selenium deficiency. Both low zinc and antioxidant status can also impair the conversion of T4 (precursor) to T3 (active) hormone. The most concentrated dietary source of selenium is the Brazil nut, because the soil where Brazil nuts are grown is particularly rich in selenium.
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Chromium is a trace metal that plays a role in metabolizing carbohydrates. It is the central molecule of glucose tolerance factor (GTF), a compound that helps insulin attach to a cell’s receptors. This allows glucose to be taken up by a cell and used for fuel, rather than continue circulating in the bloodstream and eventually wreaking havoc on blood vessels and organs.
When chromium is deficient in the body, glucose cannot be metabolized properly. This sets the stage for insulin resistance. The good news is that when a chromium deficiency is corrected, blood sugar regulation improves. Unfortunately, supplemental chromium, such as chromium picolinate, may not be absorbed efficiently. Chromium competes for the binding site of a protein that transports iron, which may also inhibit absorption. The solution? Increase your dietary intake of chromium-containing foods. Among the best sources of this mineral are broccoli, barley, oats, and green beans. You’ll want to limit your intake of foods high in simple sugars, on the other hand, as these actually increase the rate of excretion, thus promoting chromium deficiency.
Also known as pantothenate or pantothenic acid, vitamin B5 is sometimes referred to as the “anti-stress” vitamin because it can reverse some biological damage caused by stress. Physical, emotional, and psychological stresses trigger the adrenal glands to secrete cortisol (a long-term stress hormone) and adrenaline (a short-term stress hormone). Chronic stress drives the production of too much of any of these hormones, which causes damage in the body long after the stress signal has ended. When vitamin B5 is present in adequate amounts, it is able to down-regulate the secretion of cortisol, and the body is able to recover. However, in a deficiency state, the adrenal glands are unable to cope. Under these circumstances, they cannot launch a healthy response against the multiple daily stressors that assail us, and the chronic (often unavoidable) stress eventually takes a physiological toll.
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Magnesium is predominantly found intracellularly, where it is vital for proper cell functions. Magnesium is the second most prevalent intracellular cation (after potassium). Magnesium functions are numerous and essential, including enzyme activation (over 300 types), neuromuscular activity, membrane transport and interactions, energy metabolism (carbohydrates, fats, proteins), and roles in calcium and phosphorus metabolism.
Deficiency symptoms are both acute (Trouseau and Chvostek signs, muscle spasms, tetany, cardia arrythmias, ataxia, vertigo, convulsions, organic brain syndrome) and chronic (thrombophlebitis, hemolytic anemia, bone loss, depressed immune function, poor wound healing, hyper irritability, burxism, hyperlipidemia, fatigue, hypertension). Those at risk for Magnesium deficiency include: malabsorption, malnourished, alcoholics, diabetics, diuretic therapy, children, elderly, pregnant and lactating women, post menopausal women with osteoperosis, athletes, digitalis therapy, long-term therapy with antibiotics, chemotherapeutic and immunosuppressive medications. In addition, the following diseases are associated with Magnesium deficiency: cardiovascular disease, cirrhosis, renal disease, parathyroid diseases, thyroid conditions.
Dietary sources richest in Magnesium (per serving) are:
Seeds (especially pumpkin)
Watch or download Dr. Grabowski's presentation on "Connecting the Nutrients" here