Sepsis and infection treatments in hospital or via doctors often rely on antibiotics while missing unused iron as possible factor feeding the infection.
If someone is anaemic this can be seen as cause of immune failure and iron supplementation or blood transfusions can be given which pathogens can use as a food source.
‘…..the growing literature linking Iron to both impaired immunity and heightened microbial virulence, calls into question the value of Iron supplementation during inflammation and infection. Iron and the risk of infection
Blood transfusions and antibiotic infusions are also expensive treatments requiring equipment and the expertise of nurses and doctors to fit cannulas into patients.
Intravenous cannulas which are generally inserted into the arm can come out and confused patients will often pull them out, all requiring extra attendance.
The treatment options almost always missed in a hospital setting are the nutrients needed to treat anaemia and iron absorption.
The idea to convey is iron we need for our blood cells needs to be absorbed into the blood before any ‘bacteria, a virus, fungi or protozoa’ can get the iron to feed on and replicate.
The main nutrients are Vitamin C, Vitamins B6, B12, Folate and Copper.
The main one used in hospital is Vitamin B12, doctors may prescribe Vitamin C and Folate to help with anaemia, but if iron levels are high few of these nutrients are used to help blood cells absorb the iron before any infections get the iron.
If hypoxia or acidosis is occurring with an infection then Vitamins B1 and B3 may be needed as I have written here, I call this a ‘breathing protocol’.
Vitamins B1 and B3 Would Save Millions Spent on Sepsis, Hypoxia and COVID
‘Sepsis can start with infection by bacteria, a virus, fungi or protozoa. The initial infection can be anywhere in the body, like in the bladder or abdomen (the gut), or in the chest, or even on the skin. With sepsis, the body’s immune reaction to the infection causes a large inflammatory response which makes things worse, not better.’
Think outside of the box when you have an infection.
Most people will think ‘I have such and such bacteria’ and I am taking the prescribed antibiotic that suits that bug, that’s OK, the doctor should be giving the appropriate antibiotic to deal with that bug.
You also need to think ‘Am I anaemic or do I have too much iron?
If you can read your own blood tests the indicator is high Ferritin levels.
‘Serum ferritin >300 ng/ml in males and greater than 150 to 200 ng/ml in menstruating females can indicate iron overload.’ Iron Overload
If I saw high Ferritin levels in a patient with infections then that to me is a big alert to the bacteria or fungi is using the iron as a nutrient to replicate.
Any infections should be treated with vitamin C as it helps absorb iron and also Vitamin C is used by our white blood cells in large quantities to deal with illness.
Ask ‘Do I eat fresh fruit, vegetables that are not overly cooked or take vitamin C supplements?’, are you also in hospital as hospital food is generally cooked and low in Vitamin C.
Vitamin B6 is the next to absorb ‘free iron’, between 50mg and 100mg of B6 a day prevents iron deposition in organs and is the most missed vitamin for preventing anaemia, the others are Folate from vegetables and B12 from meat.
Low B12 is often detected and addressed with B12 supplementation by doctors.
Folate is also often noticed, but again ask yourself ‘Do I eat fresh fruit or vegetables that are not overly cooked?’ as Folate comes from them.
Also if you are vegan or vegetarian are you getting B12?
This summary says B6 deficiency is rare, B6 is also an antidepressant and insomnia aid as it helps serotonin/melatonin creation, given the almost epidemic levels of depression and insomnia I would say B6 deficiency is common as scurvy.
‘If your body is very low on B6 (which is rare), you can get anemia, which is too few red blood cells. That would make you feel tired and weak. Anemia can also come from not having enough iron in your body. Shortages of other vitamins, like B12 and folate, also may cause it.’ Signs You’re Not Getting Enough Vitamin B6
The last one to note is copper as it is needed to absorb the iron as well.
This is well summarised by Dr Lauren Deville to keep it understandable.
‘Copper and Hemoglobin
About 90% of copper in the blood is bound to ceruloplasmin, with the rest bound to albumin and amino acids. Ceruloplasmin oxidizes (removes an electron from) iron absorbed from the gut and stored in the tissues so that it can be transported by transferrin (the iron transport protein) and eventually used to form new red blood cells. Less copper means less ceruloplasmin, which means iron can’t get shuttled where it needs to go to make hemoglobin.
This is why low copper can lead to iron deficiency anemia.
‘Why Might You Be Low in Copper?
Copper isn’t stored well, so it has to be consumed from foods. It can be found in high doses in organ meats, seafoods, beans, nuts, and whole grains.’
When Iron Deficiency is Really Copper Deficiency
Copper is also in cocoa and chocolate, bacteria and fungi also don’t like copper.
Just be aware that copper from things like cocoa or nuts can cause constipation without enough vitamin C or magnesium in the diet.
If you are suffering from diarrhea then chocolate or cashews work quickly to solid up so don’t be scared of chocolate, avoid ice cream and too much sugar.
To summarise, if you have an infection do you have anaemia or could your iron levels be too high, either way the nutrients to help red blood cells form could remove the iron from being used by any ‘bacteria or fungi’ and they are Vitamin C, Vitamins B6, B12, Folate and Copper.
Be aware that iron supplements should be used after getting enough B Vitamins and Vitamin C.
Iron and Immune Studies
These are all useful if you want to understand the concepts but I tried to leave them out of the introduction to keep things simple.
This study describes how we have immune systems that actually create anaemia to prevent iron being used by pathogens.
As an aside the old practice of ‘blood letting’ was a mechanical way of removing iron from the body to prevent infections.
“Iron is an essential nutrient for both humans and pathogenic microbes. Because of its ability to exist in one of two oxidation states, iron is an ideal redox catalyst for diverse cellular processes including respiration and DNA replication. However, the redox potential of iron also contributes to its toxicity, thus iron concentration and distribution must be carefully controlled. Given the absolute requirement for iron by virtually all human pathogens, an important facet of the innate immune system is to limit iron availability to invading microbes in a process termed nutritional immunity. Successful human pathogens must therefore possess mechanisms to circumvent nutritional immunity in order to cause disease.”
“Iron metabolism is tightly regulated to avoid both cellular damage associated with iron overload, and anemia associated with iron deficiency.”
“In addition to mitigating toxicity associated with hypo- or hyperferremia, regulation of iron distribution serves as an innate immune mechanism against invading pathogens. Even in the absence of infection, several facets of human iron metabolism ensure that iron is scarcely accessible to pathogenic microorganisms. First, the majority of iron in humans is sequestered intracellularly, complexed within hemoglobin inside erythrocytes. Some pathogens have therefore evolved mechanisms to liberate hemoglobin by lysing erythrocytes to ultimately extract iron from heme. However, hemolytic pathogens must subsequently compete with haptoglobin and hemopexin, host glycoproteins that scavenge liberated hemoglobin and heme, respectively. A second factor limiting the availability of iron to invading pathogens is the paucity of free extracellular iron. Extracellular iron is bound with high affinity by transferrin, which in healthy individuals is typically less than 50% saturated with iron. When transferrin binding capacity is exceeded, iron can also be chelated with lower affinity by a number of molecules in plasma including albumin, citrate, and amino acids.”
“Hepcidin is a major orchestrator of the hypoferremic response to infection. In fact, hepcidin was initially characterized as an antimicrobial peptide in human urine and blood ultrafiltrate. Hepcidin release from the liver is stimulated by pro-inflammatory cytokines, TLR activation, and induction of the endoplasmic reticulum unfolded protein response. In addition to hepcidin production in the liver, neutrophils and macrophages synthesize hepcidin in response to infectious agents, allowing for modulation of iron availability at the infectious focus.”
“Lactoferrin is a host glycoprotein that, like transferrin, binds free iron with high affinity. Mucosal secretions contain high concentrations of lactoferrin, comprising a constitutive mechanism for iron limitation at mucosal surfaces. Additionally, the specific (“secondary”) granules of neutrophils contain lactoferrin, which is released at infectious sites in response to cytokines. Moreover, unlike transferrin, lactoferrin maintains iron-binding capacity at low pH and therefore may be a more effective scavenger in acidotic infectious foci.”
“Individuals suffering from iron overload not only experience cellular damage from adverse redox chemistry of free iron, but also are at enhanced risk of infection.”
“Patients suffering from hemochromatosis develop iron deposits in organs such as the heart and liver, leading to oxidative damage, liver dysfunction and cardiomyopathy.”
“Regardless of the underlying etiology, the availability of iron to invading pathogens is enhanced during iron overload, and such individuals therefore have an increased susceptibility to a variety of infectious diseases.”
“Ferritins and bacterioferritins enhance growth of iron-starved pathogens such as E. coli, Campylobacter jejuni, and Helicobacter, pylori protect against redox stress, and contribute to survival within the host. For example, disruption of Mtb (Tuberculosis) ferritin biosynthesis limits resistance to oxidative stress, enhances susceptibility to antibiotics, and decreases bacterial survival in a chronic infection model”
“Pathogenic fungi, like bacterial pathogens, must obtain iron from host tissues and regulate iron homeostasis to avoid toxicity. Furthermore, iron serves as an important signal for some fungi during the transition from a commensal lifestyle to that of an invasive pathogen”
“Parasitic infections are a substantial source of morbidity and mortality worldwide. The link between endoparasitic infection and human iron homeostasis is, in some cases, quite direct.”
Iron in Infection and Immunity
Too much iron also affects immune cells.
“Iron overload leads to inhibition of IFN-gamma, TNF-alpha, IL-12, and nitric oxide formation as well as impairment of macrophage, neutrophil, and T-cell function. Injection of Fe into mice and rats markedly increases the virulence of several pathogens. Studies in hemodialysis patients have documented an association between infection and increased ferritin concentration as a surrogate marker for Fe overload.”
“Humans respond to infection with inflammatory cytokine-induced hypoferremia. This association, as well as the growing literature linking Fe to both impaired immunity and heightened microbial virulence, calls into question the value of Fe supplementation during inflammation and infection.”
Iron and the risk of infection
‘Derangements of iron metabolism may be present in critically ill patients who develop anemia during a stay in the intensive care unit. Iron supplementation may be appropriate, especially if an underlying nutritional disorder is present. It may be even more critical to replace iron when erythropoietin therapy is used because of the consumption of iron stores that occurs during heme synthesis. Iron therapy is not without risks, and controversy persists regarding the potential for iron overload and infections.’
Iron supplementation in the intensive care unit: when, how much, and by what route?
During an infection an inflammatory cytokine called IL-6 can stimulate Hepcidin which in turn blocks iron from being used and causes a form of anaemia.
‘IL-6 acts directly on hepatocytes to stimulate hepcidin production. Hepcidin, in turn, acts as a negative regulator of intestinal iron absorption and macrophage iron release.’
Anemia of inflammation: the cytokine-hepcidin link
Vitamin B3 or Nicotinamide is a vitamin that lowers IL-6.
‘As the proinflammatory cytokine response of IL-1β, IL-6, IL-8 and TNFα following endotoxin stimulation of human whole blood is profoundly inhibited by nicotinamide, nicotinamide may have a therapeutic potential as a modulator of cytokine effects in inflammatory disease.’
Nicotinamide is a potent inhibitor of proinflammatory cytokines
In this article on iron and infections the main message is how we can use iron before pathogens can use our iron so I concentrated on the anaemia nutrients.
As a further protocol for preventing immune failure the nutrients needed are Vitamin B3 or Nicotinamide, Vitamin B6 and the amino acid Trytophan to prevent ‘Indoleamine 2,3-dioxygenase activity’.
I wrote this as a guide to understanding IDO enzymes.
Macrophage Polarization and IDO Enzymes, Immunity, Cancer and Depression
‘A key enzyme upregulated in alternatively activated macrophages is indoleamine 2,3-dioxygenase, which converts tryptophan to kynurenine for de novo synthesis of nicotinamide. Nicotinamide can be used to replenish cellular NAD+ supplies. We hypothesize that an insufficient cellular NAD+ supply is the root cause of metabolic shifts in macrophages. We assert that manipulation of nicotinamide pathways may correct deleterious immune responses.’
Lowering IDO enzymes with Vitamins B3, B6 and Trytophan is another pathway to preventing anaemia and keeping iron away from pathogens.
Hence the importance of Vitamins B3 and B6 as immune stimulants.
‘An increased indoleamine 2,3-dioxygenase activity with an enhanced degradation of tryptophan is also considered to be involved in the drop of blood levels of haemoglobin and the development of anaemia.’
This is a practical observation on how much 100mg of Vitamin B6 can achieve.
‘Patients undergoing a panic attack (PA) or a hyperventilation attack (HVA) are sometimes admitted to emergency departments (EDs). Reduced serotonin level is known as one of the causes of PA and HVA. Serotonin is synthesized from tryptophan. For the synthesis of serotonin, vitamin B6 (Vit B6) and iron play important roles as cofactors.
‘We found that both Vit B6 and iron levels were significantly lower in the PA/HVA group than in the volunteer group. There was no significant difference in the serum levels of vitamins B2 or B12. These results suggest that low serum concentrations of Vit B6 and iron are involved in panic attacks and hyperventilation attacks.’
Hypoxia effects on iron release and Vitamin B1 protection.
Again I will refer to my article on sepsis here which details B1 effects on breathing.
Vitamins B1 and B3 Would Save Millions Spent on Sepsis, Hypoxia and COVID
Along with the nutrients to absorb iron, Thiamine or Vitamin B1 could be the extra nutrient needed in high doses to prevent iron damage from hypoxia and acidosis.
When the blood gets low in oxygen (hypoxia), transferrin which moves iron to the blood increases to enable more red blood cells to carry oxygen for the body.
Making low oxygen a risk for blood clots and stroke.
‘In this issue of Blood, Li et al1 demonstrate that hypoxic conditions in mice or in humans living at high elevation led to increased transferrin expression and a risk of thrombosis.’
Transferrin-induced thrombosis in hypoxia
‘Furthermore, both hypoxia (6% O2) and low temperature (0°C), 2 critical high-altitude factors, enhanced hypoxia-inducible factor 1α (HIF-1α) levels to promote the expression of the transferrin gene, whose enhancer region contains HIF-1α binding site, and consequently, to induce hypercoagulability…..’
Hypoxia and low temperature upregulate transferrin to induce hypercoagulability at high altitude
Low Thiamine levels make hypoxia-inducible factor 1α (HIF-1α) levels rise making hypoxia worse, this all crosses over into effects on nerve and brain diseases.
‘Insufficiencies of the micronutrient thiamine (Vitamin B1) have been associated with inducing Alzheimer’s disease (AD)-like neuropathology. The hypometabolic state associated with chronic thiamine insufficiency (TI) has been demonstrated to be a contributor towards the development of amyloid plaque deposition and neurotoxicity. However, the molecular mechanism underlying TI induced AD pathology is still unresolved. Previously, we have established that TI stabilizes the metabolic stress transcriptional factor, Hypoxia Inducible Factor-1α (HIF1α).’
Thiamine thus has protective effects by reducing hypoxia and acidosis.
Severe lactic acidosis reversed by thiamine within 24 hours
‘Thiamine deficiency impairs the integrity of the blood‐brain barrier, thereby enabling iron to pass through and accumulate in the brain.’
Does thiamine protect the brain from iron overload and alcohol‐related dementia?
The concept to understand is the iron being moved by transferrin is vital but less dangerous if Vitamin B1 levels are adequate to provide protection, and the other nutrients such as Vitamin C, B6, B12 and Folate are high enough to allow red blood cells to use the iron.
Here is an example of transferrin causing arterial damage from iron release.
‘Low density lipoprotein (LDL) oxidation within the arterial wall may contribute to the disease of atherosclerosis. We have investigated the conditions under which transferrin (the major iron-carrying protein in plasma) may release iron ions to catalyse the oxidation of LDL.’
The release of iron from transferrin in atherosclerotic lesions due to a localised acidic pH may help to explain why LDL oxidation occurs in these lesions.
Iron released from transferrin at acidic pH can catalyse the oxidation of low density lipoprotein
So for sepsis patients getting iron in the blood is the key to getting better.
While high ferritin indicates unused iron is there for pathogens to use.
‘Septic patients have low iron and transferrin levels, associated with high ferritin levels, and those levels improved during the course of disease….’
Vitamin C and Sepsis.
These studies summarise why Vitamin C is needed.
Again, I have to emphasise that Vitamin C is rarely used in hospitals, there will be a few orange juices given if asked, if someone asks for a salad they will get the best source of Vitamin C from a meal like that but very few people ask for salads.
In general everything is cooked and provides protein, carbohydrates and the nutrients from cooked vegetables but always low in C.
‘Evidence is emerging that parenteral administration of high-dose vitamin C may be a beneficial adjuvant therapy of severe sepsis and septic shock. An excessive inflammatory response indeed enhances metabolic turnover of vitamin C. As a result, patients with severe sepsis often have very low plasma vitamin C levels that sometimes enter the “scurvy” zone. In animal models of sepsis, intravenous ascorbate rapidly and persistently improved capillary and microcirculatory blood flow, decreased microvascular permeability, and attenuated inflammation. Vitamin C also restored endothelial barrier function, prevented apoptosis, and exerted antibacterial effects.’
‘Accumulating evidence strongly suggests that in addition to the known ability of dietary ascorbate to enhance nonheme iron absorption in the gut, ascorbate within mammalian systems can regulate cellular iron uptake and metabolism. Ascorbate modulates iron metabolism by stimulating ferritin synthesis, inhibiting lysosomal ferritin degradation, and decreasing cellular iron efflux. Furthermore, ascorbate cycling across the plasma membrane is responsible for ascorbate-stimulated iron uptake from low-molecular-weight iron-citrate complexes, which are prominent in the plasma of individuals with iron-overload disorders. Importantly, this iron-uptake pathway is of particular relevance to astrocyte brain iron metabolism and tissue iron loading in disorders such as hereditary hemochromatosis and β-thalassemia. Recent evidence also indicates that ascorbate is a novel modulator of the classical transferrin-iron uptake pathway, which provides almost all iron for cellular demands and erythropoiesis under physiological conditions. Ascorbate acts to stimulate transferrin-dependent iron uptake by an intracellular reductive mechanism, strongly suggesting that it may act to stimulate iron mobilization from the endosome. The ability of ascorbate to regulate transferrin iron uptake could help explain the metabolic defect that contributes to ascorbate-deficiency-induced anemia.’
Macrophages or white blood cells use enormous amounts of vitamin C as does blood plasma, I will show examples.
‘To test whether ascorbic acid might be involved in the antioxidant defenses of inflammatory cells, we studied ascorbate uptake and recycling by quiescent and lipopolysaccharide-activated RAW264.7 murine macrophages. These cells concentrated ascorbate 100-fold in overnight culture….’
Macrophage uptake and recycling of ascorbic acid: response to activation by lipopolysaccharide
‘In this paper, we show that it is indeed ascorbate that completely protects plasma lipids against detectable peroxidative damage induced by aqueous peroxyl radicals and that ascorbate is the only plasma antioxidant that can do so. Plasma devoid of ascorbate, but no other endogenous antioxidant, is extremely vulnerable to oxidant stress and susceptible to peroxidative damage to lipids.’
‘Our data demonstrate that ascorbate is the most effective aqueous-phase antioxidant in human blood plasma and suggest that in humans ascorbate is a physiological antioxidant of major importance for protection against diseases and degenerative processes caused by oxidant stress.’
Ascorbate is an outstanding antioxidant in human blood plasma.
An old account of scurvy here.
“After a few months at sea the first symptoms would appear: an awful lassitude, with terrors and depression, followed by a rash which oozed blood from hair follicles on the body and legs, and by swollen joints. About a fortnight later the gums would swell, bleed and rot, and the teeth would become loose and fall out. Suppurating sores might develop on the body, and the bones would be racked by a terrible pain. As often as not, men with scurvy would suddenly drop dead as they dragged themselves about their work.
Strangest of all, old, healed wounds would reopen like a ghostly vengeance.”
This is how much vitamin C COVID patients could have.
‘To our knowledge, this is the first study to analyze the levels of vitamin C in patients with SARS-CoV-2-associated ARDS. Our study revealed that vitamin C levels are undetectable in more than 90% of the patients included. The mechanisms of this significant reduction in vitamin C are uncertain. We hypothesized that several mechanisms, such as increased metabolic consumption due to the enhanced inflammatory response, glomerular hyperfiltration, dialysis, decreased gastrointestinal absorption, or decreased recycling of dehydroascorbate to ascorbic acid, may be involved.
Moreover, vitamin C may have implications for treatment of COVID-19-associated ARDS. Indeed, one preclinical study showed that vitamin C increased resistance to infection caused by coronavirus. Moreover, other clinical studies that included surgical patients and patients with pneumonia showed encouraging results in terms of decreased incidence and severity of lung injury and mortality.’
Vitamin C levels in patients with SARS-CoV-2-associated acute respiratory distress syndrome
“The patients who received vitamin C did significantly better than those who did not get vitamin C,” he said.
“It helps a tremendous amount, but it is not highlighted because it’s not a sexy drug.”
New York Hospitals Treating Coronavirus Patients With Vitamin C
I left all of the studies for people to look further.
If suffering anaemia or infections I hope this gives a guide of other actions to take.
