Levodopa + carbidopa and copper interactions are quite complex and not always apparent. The copper-iron and copper-zinc interactions add an extra layer of complexity that is not necessarily well understood.Parkinson’s disease is attributed to loss of dopamine neurons in the substantia nigra, and loss of cells in the hypothalamus. As a cure for PD (Parkinson’s

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The interdependence of copper-iron interactions, and their importance in health management, remains overlooked and under-researched. Deficiencies or excesses of either mineral alters the effect of the other, and may alter local and general physiological processes. Intake sourcesThree key sources of copper (Cu) and iron (Fe) availability include -Dietary intake – includes both volume of foodstuffs

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Levodopa + carbidopa and iron interactions are both complex and extensive. The theories for many of these interactions are speculative, and sustained with reasoned argument, however supporting evidence is very limited.Parkinson’s Disease (PD) is a progressive, neurodegenerative disorder that includes slow movements, rigidity and freezing, and sustained tremor. Dopamine deficiency is considered the main cause

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Drug-induced tipping points and health management strategies are an unlikely combination and rarely considered. A common definition (https://global-tipping-points.org/what-is-a-tipping-point/) for a tipping point is –   – where a small change makes a big difference to a system (Gladwell [debut novel], 2000), or   – the point at which a series of small changes or incidents becomes significant

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Levodopa + carbidopa and thiamine encompass a range of interactions that have significant consequences to Parkinson’s Disease (PD) progression.The majority of people diagnosed with PD are treated with medications to relieve the symptoms of the disease. The medications fall into 2 primary groups, being — levodopa-based which stimulate the remaining cells in the substantia nigra

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Levodopa + carbidopa and vitamin C encompass a range of interactions that include both direct and indirect mechanisms of action. Parkinson’s disease (PD) is a common, progressive neurological nasty for which there is no cure – only management of symptoms. PD’s symptoms typically include tremors, rigidity, slow movement, poor balance, difficulty walking, and facial masking.

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The levodopa + carbidopa and vitamin D interaction is apparently additive however the evidence is limited. Given Parkinson’s Disease is considered the number 1 neurological nasty, this is quite surprising.Parkinsons Disease (PD) is primarily a dopamine deficiency that causes loss in the substantia nigra component of the brain.As PD is currently considered incurable, management remains

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Levodopa + carbidopa and zinc interactions are a surprisingly relatively recent finding. Levodopa is both a pharmaceutical and an amino acid that is naturally present in the body. Further, levodopa is a dopamine precursor that can cross the blood-brain-barrier (BBB), and is the brain’s primary source of dopamine. Carbidopa confers the dual benefits of –

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Is there evidence of a levodopa +carbidopa and manganese interaction? The total metal content and cellular compartmentalization of several key metals including manganese was examined in those with Parkinsons Disease (PD) (https://doi.org/10.1039/c7mt00244k).The 3 regions selected in this study were because of their responses to Parkinson’s disease, and include -Substantia nigra – the primary site of

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The levodopa + carbidopa, magnesium and vitamin C interaction has only recently gained recognition. Levodopa is commonly prescribed for those diagnosed with Parkinson’s Disease. Carbidopa’s primary function is to minimise B6’s impairment of levodopa absorption. Recent evidence (https://doi.org/10.1016/j.prdoa.2023.100227) indicates concurrent administration of magnesium oxide (MgO) with levodopa + carbidopa decreases their absorption and availability. The

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Interactions between aspirin and various nutrients have been identified over a number of decades and are either old, forgotten, or have no supporting references, and therefore require clarification with regard to current status.Nutrients for which there is relatively recent evidence -1. Vitamin E. The proposed aspirin-vitamin E interactions generally refer to possible additive antithrombotic effects,

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An aspirin-folic acid interaction was a recent “incidental finding” from a pooled analysis of some studies looking at brain atrophy response to a B vitamin intervention. The population-based studies consistently identified a negative aspirin-folic acid interaction in those with cognitive impairment, however the mechanism(s) of action remains speculative. The aspirin-folic acid interaction was initially discovered

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The aspirin-vitamin C interaction was discovered in the early 1970’s. Much of the evidence is based on short term, high-dose interventions and there is minimal evidence in relation to low-dose, long term interventions. Currently there are no commonly prescribed clinical interventions for this interaction.Vitamin C transporters include -SVCT1 (Sodium Vitamin C Transporter 1) – primarily

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Osmolality seems to be a rarely-considered contributor to a range of primarily gastro-intestinal side effects – and is probably overlooked because osmolality data is difficult to access; there is no regulatory requirement for its inclusion in the Product Information document.Osmolality is a measure of the number of solute particles per kilogram of solvent and is

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“Not to be crushed, chewed, broken or dissolved” and its many variations are commonly included in most medicines Product Information documents. Therefore, if a medicine is crushed, chewed, broken or dissolved to ensure safe administration then there is non-compliance with manufacturer’s instructions. Further, crushing, chewing, breaking or dissolving a medicine means alteration to some aspects

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Excipients are the ingredients that comprise about 90% of a medicine – they are added to optimise some aspect of the medicine’s administration and/or therapeutic benefit. Excipients seem to have 3 key roles, being -to negatively impact pathophysiology (injury- or disease-caused upset physiological processes),starting points for drug discovery projects,treatment enhancers as functional supplements.Functional roles of

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“Not clinically relevant”, “inhibition unlikely at therapeutic interventions”, “clinical inhibition deemed minimal”, and similar other phrases typically refer to drug-transporter interactions; the phrases such as “at this dose” or similar, are also generally included and all relate to drug-drug interactions only. From a nutrition perspective, these phrases are red flags as indirect nutrition impacts are

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The side effects of many prescribed medicines include altered glycaemic status which is associated with physical harm to the body. Glycaemia (blood sugar levels) are variable and at times can be either too high (hyperglycaemia) or too low (hypoglycaemia). Both hyperglycaemia and hypoglycaemia are associated with oxidative stress which is considered a primary cause of

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Multidrug resistance proteins (MRPs) are efflux transporters and as such are responsible for the movement of a wide variety of both endobiotics (endogenous substances that influence the functioning of an organ or biological process. [Wiktionary]) and xenobiotics (foreign compounds not produced by an organism’s metabolism, or biological substances present in excessive concentrations), across plasma and

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This email is based on a question from a concerned clinician.Oral calcium intake – no evidence of excessive calcium intake in diet, and no high-dose calcium supplements prescribed.Pathology results -PTH (parathyroid hormone) normal;calcium ~ 2.7ish mmol/L (elevated), some degree of fluctuation.Prescribed medications – fluoxetine, olanzapine.Nutrient supplements – multivitamin, zinc.Fluid intake – 3 L water/day (therefore

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Role/functionOATs are primarily influx transporters albeit some are bidirectional, that with their multi-specific binding pockets are able to transport a wide variety of anionic and cationic substances into the kidney and then regulate their rate of excretion.OATP IsoformsThere are 11 known human isoforms as summarised -OAT1Included in drug discovery processes to minimise drug-drug interactionsRoleprefers hydrophilic

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Permeability-glycoprotein is known as P-glycoprotein or P-gp or multidrug resistance protein (MDR1/2); it has a large and versatile drug-binding region that encompasses multiple and overlapping binding sites inside a large and flexible binding pocket lined with aromatic residues that can accommodate a large range of smaller or larger molecules or several molecules simultaneously, and is

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The Sodium Vitamin C Transporters (SVCTs) regulate vitamin C homeostasis (system stability) such that excessive intakes result in reduced intestinal absorption and renal reabsorption, and inadequate intakes result in increased intestinal absorption and renal reabsorption.The SVCT1/2 substrate is the reduced form of vitamin C/ascorbic acid ie ascorbate.There are 3 identified SVCTs, being –SVCT1 – is responsible

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Multi drug and toxin exclusion transporters (MATE1) and (MATE2) are major efflux transporters involved in the hepatic and renal excretion of many cationic endogenous and xenobiotic substances. As efflux transporters they primarily move lipophobic substances -out of the liver ie hepatic biliary excretion – MATE1,out of the kidneys and into urine ie renal excretion –

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Breast Cancer Resistance Protein (BCRP) seems to be an initial defence against environmental insults such as phototoxic skin lesions, and xenobiotic absorption, and seems to prefer to excrete toxic substances via the biliary pathway. BCRP overlaps with P-glycoprotein (aka P-gp, or MDR1) and to a lesser extent with MRP1 (Multi Resistance Protein) – whether there

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The thiamine transporters Thiamine Transporter 1 (THTR1) and Thiamine Transporter 2 (THTR2) transfer thiamine and pyridoxine, and are associated with two transfer systems, being -THTR1 – the nutrient concentration is low and therefore uptake requires energy,THTR2 – the nutrient concentration is high (thiamine > 2 mmol/L), and therefore uptake involves passive nutrient diffusion.THTR1 and THTR2

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Sodium Multivitamin Transporter (SMVT) facilitates the uptake of biotin, pantothenic acid, lipoic acid, and iodine from the gut and across the Blood Brain Barrier. SMVT is the only currently known intestinal biotin transporter. SMVT is present in the small and large intestines, liver, kidney, heart, lungs, brain, cornea, retina, and placenta tissues.As a consequence of

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The organic cation transporters regulate the transfer of many essential organic cations across biological membranes and therefore have an essential role in many metabolic processes.OCTs are known as being polyspecific transporters because they recognize and transport a broad range of substances such as the organic amines choline and carnitine, the neurotransmitters dopamine and serotonin, and

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Membrane transporters enable substances to cross impermeable cell membranes. Whilst they primarily transfer endogenous substances such as nutrients, they can also transfer exogenous substances such as toxic metals, pharmaceuticals, and other toxic substances. Membrane transporters function similarly to shuttle buses in that they efficiently move substances from one area to another – some only offer one-way

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Metformin’s role in healthcare management is expanding and is now being considered as a treatment for some cancers, bone health, neurodegeneration, and probably others, as well as its long-recognised role in diabetes management.The mechanisms by which metformin exerts its effects are still not fully understood but it is currently accepted that metformin inhibits glucose production

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The mechanisms by which metformin exerts its effects are not fully understood and current concepts are currently being challenged. However, it is known that metformin inhibits glucose production in the liver and increases glucose uptake in peripheral tissues thereby lowering blood glucose levels.Metformin’s accepted function is that it slows mitochondrial respiration by inhibiting -NADH-ubiquinone oxidoreductase

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Aspects of pyridoxine and pharmaconutrition have been written about in previous posts –Metformin & B6,Elevated pyridoxine and pharmaconutrition,B6 absorption requires an acid environment,Pyridoxine and pharmaconutrition.This post is a summary and update with a focus on metformin’s negative impacts on pyridoxine. Summarized functions Vitamin B6 is a generic name for about 6 different compounds and is important in

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Metformin is a commonly prescribed first line intervention in NIDDM management and its mechanisms of action include decreased intestinal sugar absorption, increased glucose uptake in liver and skeletal muscle, modulation of lactate production, inhibition of gluconeogenesis and protein synthesis, activation of fatty acid β-oxidation, and reduction in appetite.Vitamin D deficiency is being called a pandemic

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Metformin was developed and released in the late 1950’s and within a decade was identified as a cause of B12 deficiency. More recently, other nutrients have also been identified as being negatively impacted by metformin, including magnesium, thiamine, riboflavin, folate, pyridoxine and vitamin D. Cobalamin aka Vitamin B12 is a fully diet-dependent vitamin as it

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In many countries, metformin is the first prescribed therapeutic intervention for those diagnosed with Type 2 diabetes. Metformin primarily increases insulin sensitivity, promotes weight loss, lowers death rates from all causes, decreases cancer risk, and lowers risk of atherosclerosis and heart disease.Folate or folic acid, is an essential vitamin with multiple functions including being essential

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A throw-away comment in a relatively recent paper that metformin was associated with diminishing riboflavin status prompted this post.Although metformin can be prescribed for decades there is remarkably limited evidence in relation to its negative impacts on various nutrients, and especially riboflavin.Riboflavin is important in cancer therapy, malarial infection control, angiogenesis, erythropoiesis, male fertility [by

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Membrane transporters are steadily gaining recognition as important factors in the absorption, distribution, metabolism, and excretion of many nutrients, as well as many xenobiotic compounds such as prescribed medicines, toxic metals, many agricultural chemicals.The combination of polypharmacy and the current regulatory requirements, necessitate all new drugs be evaluated for their impact on a predetermined range

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Metformin is the fourth most commonly prescribed medicine in the world therefore it’s negative impacts on nutritional factors affects a significant percentage of the global population.Hypomagnesaemia in people diagnosed with diabetes is reported to be about 31%, based on a lower acceptable limit for magnesium of 0.70mmol/L. There is a recommendation for a universal lower

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Coagulation (blood clotting) is a process that prevents excessive bleeding when a blood vessel is injured. Usually, a blood clot dissolves once the injury has healed however sometimes a clot will form inside a blood vessel without any obvious injury and/or may not dissolve naturally.Vitamin K is commonly associated with the coagulation process however there

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DOACs (direct oral anticoagulants) are becoming the preferred option for coagulation management because they do not require the management strategies that warfarin administration necessitate such as regular and frequent INR monitoring, significant dietary restrictions, OH&S concerns relating to internal bleeds, etc especially for farmers, and elderly fallers.Evidence indicates the individual macronutrients, being proteins, fats and

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The warfarin-vitamin K interaction is well-known and so those prescribed warfarin are typically “educated” about vitamin K containing foodstuffs, however there is minimal advice regarding warfarin interactions with other foodstuffs.Whilst some warfarin-food interactions are related to Vitamin K content there are other interactions with alternate mechanisms of action.Vitamin K content – inhibits coagulationAvocado – has

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Warfarin is an anticoagulant for which there is a well-known coagulation interaction with vitamin K however its interactions with other nutrients are less well-known.Warfarin is a substrate and inhibitor for the transporters OAT1/2, and it is carried in the blood by albumin and alpha-1 acid glycoprotein.Transporters OAT1-4 mostly shuttle from blood into kidneys.Warfarin also interacts

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Vitamin K encompasses several compounds that have similar structures and physiological functions –vitamin K3 – the basic, simplest form with metabolic intermediary roles; not available in the diet;vitamin K1 – aka phylloquinone, available from plant sources; low bioavailability which is improved with the addition of lipids; relatively heat stable; light sensitive;vitamin K2 variants – aka

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Medications, medicines, drugs are used interchangeably to describe chemical substances that are administered to confer therapeutic benefit; they interact with 3 key groups –Other medicines – aka drug-drug interactions,Nutrients – aka drug-nutrient interactions,Foods – aka drug-food interactions.Drug-drug interactions are well researched, and many facets of these interactions are included in the drug discovery process. The

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Acid-base imbalance is now being associated with a range of Western health disorders including insulin resistance, diabetes, thyroid function resistance, osteoporosis, altered osteoclast and osteoblast activity, heart disease, hypertension, albuminuria, impaired renal function, chronic kidney disease, recurrent nephrolithiasis, impaired growth in children, and increased body fat in children, etc.Similar to steady state concentration, acid-base balance

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Steady state concentration is the period during which the therapeutic levels remain constant. It is achieved when a defined amount of drug excreted is equal to the amount of drug absorbed within a defined timeframe.The elimination half-life of the pharmaceutical determines the time to achieve steady state concentration, as outlined in the table -Steady state

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Insulin resistance is defined as a lack of cellular response to insulin – likely due to closed, damaged or insufficient insulin receptor sites, or some form of within-cell impairment.  The lack of cellular response to insulin causes elevated blood glucose levels (hyperglycaemia). As a consequence of hyperglycaemia the pancreas increases the rate of insulin secretion

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Insulin is a highly effective anabolic hormone that is primarily produced in the pancreas, and small amounts are also produced in some neurons.Increased plasma glucose levels trigger insulin’s release into the portal blood circulation and so it is transported to the liver which retains 50% of the insulin, the remaining 50% is released into the

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