Tag Archives: iron

Highlights of new guidelines for managing iron deficiency anemia

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Clinicians will wish to read the entire guidelines on managing iron deficiency anemia just published GUT (International Journal of Gastroenterology and Hepatology), but a few important points are worth noting here:

  • “Any level of anaemia should be investigated in the presence of iron deficiency.”
  • “Serum ferritin is the most powerful test for iron deficiency.”
  • “Gastrointestinal (GI) blood loss from colonic cancer or gastric cancer, and malabsorption in coeliac disease are the most important causes that need to be sought.”
  • “Upper and lower GI investigations should be considered in all postmenopausal female and all male patients where IDA has been confirmed unless there is a history of significant overt non-GI blood loss.”
  • “All patients should be screened for coeliac disease.”
  • “Colonoscopy has advantages over CT colography for investigation of the lower GI tract in IDA, but either is acceptable. Either is preferable to barium enema, which is useful if they are not available.”
  • “In patients with recurrent IDA and normal OGD and colonoscopy results, Helicobacter pylori should be eradicated if present.”
  • “Faecal occult blood testing is of no benefit in the investigation of IDA.”
  • “Rectal examination is seldom contributory, and, in the absence of symptoms such as rectal bleeding and tenesmus, may be postponed until colonoscopy.”
  • “Urine testing for blood is important in the examination of patients with IDA .”

Determining the cause and treating any type of anemia is of the highest importance—with even borderline anemia the ability of every cell in the body to function is impaired due to suboptimal oxygen delivery. There are a number of posts presenting studies on the depredations of mild anemia that can be seen by typing ‘anemia’ in the search box above.

Iron deficiency during infancy and early childhood may do long-lasting damage to brain development

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Even in developed nations iron deficiency is a common problem. An important clinical report just published in the journal Pediatrics examines the serious consequences, with recommendations for screening and supplementation. The authors state:

“Iron deficiency (ID) and iron-deficiency anemia (IDA) continue to be of worldwide concern…In industrialized nations, despite a demonstrable decline in prevalence, IDA remains a common cause of anemia in young children. However, even more important than anemia itself is the indication that the more common ID without anemia may also adversely affect long-term neurodevelopment and behavior and that some of these effects may be irreversible.“

The authors undertake a thorough revision and extension of the previous policy statement on ID and IDA in children last published in 1999, offering up-to-date guidelines for diagnosis and prevention in infants and toddlers aged 1 to 3. Clinicians reading this can peruse the study (the link above opens the paper in its entirety) for the specifics on acceptable hemoglobin levels and iron fortification. I encourage attention to the complications of iron deficiency, iron supplementation, and lead toxicity:

“Results of both animal and human studies have confirmed that IDA increases intestinal lead absorption…In contrast, iron supplementation in a child with IDA who also has lead poisoning without chelation therapy seems to increase blood lead concentrations and decrease basal lead excretion…Thus, in theory, selective rather than universal iron supplementation would be more likely to reduce lead poisoning and its potential harmful effects on these children.”

While lead toxicity is a problem for some, the effects of ID/IDA on neurodevelopment are universal:

“Results of a preponderance of studies have demonstrated an association between IDA in infancy and later cognitive deficits. Lozoff et al have reported detecting cognitive deficits 1 to 2 decades after the iron deficient insult during infancy.”

While the present science on this topic offers mixed evidence, the authors see fit to conclude:

“Given that iron is the world’s most common single-nutrient deficiency and there is some evidence of adverse effects of both ID and IDA on cognitive and behavioral development, it is important to minimize ID and IDA in infants and toddlers without waiting for unequivocal evidence.”

Their recommendations include these guidelines:

  1. Breastfed infants should be supplemented with 1mg/kg per day of oral iron beginning at 4 months of age until appropriate iron-containing complementary foods (including iron-fortified cereals) are introduced in the diet.
  2. Whole milk should not be used before 12 completed months of age.
  3. The iron intake between 6 and 12 months of age should be 11 mg/day.
  4. Toddlers 1 through 3 years of age should have an iron intake of 7 mg/day. For toddlers not receiving this iron intake, liquid supplements are suitable for children 12 through 36 months of age, and chewable multivitamins can be used for children 3 years and older.

Effects of suboptimal oxygen and iron on learning and behavior

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Oxygen is critical for brain function and iron is necessary to get it there. It’s worth re-visiting a study published six years ago in the journal Pediatrics that documents the profound effects of even intermittent hypoxia.

“A review of the evidence concerning the effect of chronic or intermittent hypoxia on cognition in childhood was performed by using both a systematic review of the literature and critical appraisal criteria of causality.”

The authors applied rigorous appraisal criteria to massive amounts of data narrowed down to 55 studies to resolve their findings:

“Adverse effects were noted at every level of arterial oxygen saturation and for exposure at every age level except for premature newborns.”

Their conclusions are emphatic:

“Adverse impacts of chronic or intermittent hypoxia on development, behavior, and academic achievement have been reported in many well-designed and controlled studies in children with CHD [congenital heart disease] and SDB [sleep-disordered breathing] as well as in a variety of experimental studies in adults…Because adverse effects have been noted at even mild levels of oxygen desaturation, future research should include precisely defined data on exposure to all levels of desaturation.”

Ferritin is the ‘storage’ form of iron in the bloodstream and one of the more reliable indicators of iron availability and utilization. Suboptimal ferritin can affect learning and behavior in two ways: by diminishing the oxygen-carrying capacity of the blood due to less hemoglobin, and by limiting the production of key neurotransmitters. The authors of a paper published in the journal Child Psychiatry & Human Development state:

“Our aim was to investigate the relation between behavioral symptoms and hematological variables which are related with iron deficiency and anemia, ferritin, hemoglobin, mean corpuscular volume (MCV), and reticulosite distribution width (RDW) in children and adolescents with pure Attention Deficit Hyperactivity Disorder (ADHD) or ADHD comorbid with other psychiatric disorders.”

The authors correlated results from the Conners Parent (CPRS) and Teacher Rating Scales (CTRS) the metrics for anemia and iron insufficiency. Their data showed that when ADHD was present with other problems (comorbidities) the association was pronounced:

“Comorbid ADHD subjects had lower mean hemoglogin and MCV. In the ADHD group in general, CPRS and CTRS Total scores were significantly negatively correlated with ferritin level. When only pure ADHD subjects were taken into account, the correlations did not reach statistical signifance. Overall, these results suggested that lower ferritin level was associated with higher behavioral problems reported by both parents and teachers. Presence of comorbid conditions might increase the effect of lower iron stores on behavioral measures.”

An interesting study published in the journal Sleep Medicine investigates the association of Restless Legs Syndrome (RLS) and iron deficiency on ADHD. The authors state:

“Increasing evidence suggests a significant comorbidity between attention-deficit/hyperactivity disorder (ADHD) and restless legs syndrome (RLS). Iron deficiency may underlie common pathophysiological mechanisms in subjects with ADHD plus RLS (ADHD+RLS). “

The data provided further evidence for the impact of iron deficiency on ADHD:

“The mean serum ferritin levels were significantly lower in children with ADHD than in the control group. There was a trend for lower ferritin levels in ADHD+RLS subjects versus ADHD. Both a positive family history of RLS and previous iron supplementation in infancy were associated with more severe ADHD scores.”

The authors offer useful advice to clinicians and parents in their conclusion:

“Children with ADHD and a positive family history of RLS appear to represent a subgroup particularly at risk for severe ADHD symptoms. Iron deficiency may contribute to the severity of symptoms. We suggest that clinicians consider assessing children with ADHD for RLS, a family history of RLS, and iron deficiency.”

Additional research published in Pediatrics documents further the adverse effect of intermittent hypoxia and snoring on childrens’ behavior. The authors’ objective:

“Sleep-disordered breathing is associated with impaired behavior and poor academic performance in children. We aimed to determine the extent of behavioral problems in snoring children, clarify the role of intermittent hypoxia, and test the reversibility of impaired behavior and poor academic performance.”

They included 1144 children in their study, correlating snoring, oxygen saturation with pulse oximetry, and impaired behavior using parental questionnaires and academic performance. The evidence was striking:

“HS [habitual snoring] was significantly associated with hyperactive and inattentive behavior , daytime tiredness , and sleepiness. These associations were independent of intermittent hypoxia. HS was also significantly associated with bad conduct, emotional symptoms , and peer problems.“

Moreover, although academic success did not make a big change when snoring ceased, hyperactive and inattentive behavior improved significantly. The authors conclude:

“We suggest that impaired behavior is a key feature of HS independent of intermittent hypoxia and improves when HS ceases.”

We can add to the above evidence another study published in the Archives of Pediatrics & Adolescent Medicine that also investigates the link between iron deficiency and ADHD. In addition to lower hemoglobin…

“Iron deficiency causes abnormal dopaminergic neurotransmission and may contribute to the physiopathology of attention-deficit/hyperactivity disorder (ADHD).”

Again we see serum ferritin levels correlating with the Conners’ Parent Rating Scale scores measuring severity of ADHD symptoms:

“The mean serum ferritin levels were lower in the children with ADHD…In addition, low serum ferritin levels were correlated with more severe general ADHD symptoms measured with Conners’ Parent Rating Scale…These results suggest that low iron stores contribute to ADHD and that ADHD children may benefit from iron supplementation.”

One way to prevent having a schizophrenic child

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PLoS OneAn important research article was just published in PLoS One (Public Library of Medicine) that shows a connection between the disruption of dopamine neurons when a maternal infection causes the iron supply of the fetus to drop and schizophrenia. The authors give some background:

“Maternal infection during pregnancy has been associated with increased incidence of schizophrenia in the adult offspring. Mechanistically, this has been partially attributed to neurodevelopmental disruption of the dopamine neurons, as a consequence of exacerbated maternal immunity. In the present study we sought to target hypoferremia, a cytokine-induced reduction of serum non-heme iron, which is common to all types of infections. Adequate iron supply to the fetus is fundamental for the development of the mesencephalic dopamine neurons and disruption of this following maternal infection can affect the offspring’s dopamine function.”

The authors measured the adverse behavioral and neurochemical changes from challenging the dopamine circuits with turpentine to trigger an inflammatory immune response, both with and without maternal iron supplementation. They demonstrated that…

“Both the behavioral and neurochemical changes were prevented by maternal iron supplementation.“

We already know that iron is a critical nutrient for dopamine production in the adult. Their conclusion sums up why prenatal iron status is important in preventing neurodevelopmental disorders including schizophrenia in the offspring.

Helicobacter pylori infection and iron deficiency anemia

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Postgraduate Medical JournalEven borderline anemia needs attention because it reduces the functional capability of every cell in the body. Iron deficiency anemia can sometimes respond incompletely to iron supplementation for a variety of reasons. Data from the World Health Organization (WHO) suggest that Helicobacter pylori is the most common infection in the world, with research showing links to cardiovascular disease, stomach cancer and other diseases. This paper recently published in the Post Graduate Medical Journal was inspired by the observation that…

“Recent guidelines on iron deficiency anaemia (IDA) have confirmed the aetiological role of Helicobacter pylori (H pylori), but the relationship still remains controversial.”

The authors documented data from eight studies that showed improvement in IDA with increases in hemoglobin and serum ferritin after H. pylori eradication were superior to those seen when iron was given alone. Thus their conclusion:

“H pylori eradication therapy combined with iron administration is more effective than iron administration alone for the treatment of IDA.”

Note: Helicobacter pylori infection is most accurately diagnosed by either stool antigens or a breath test for exhaled gases (not blood or stool antibodies). I have seen excellent results confirmed by follow-up tests with an evidence-based antimicrobial botanical formula.

Fibromyalgia, iron and neurotransmitters

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European Journal of Clinical NutritionMost readers are aware that low iron reduces oxygen delivery to tissues, and this degrades the ability of every cell to produce energy for function. Naturally this can contribute to chronic pain of various kinds. This valuable paper published in the European Journal of Clinical Nutrition about fibromyalgia brings up another important point: low neurotransitters (dopamine, norepinephrine, serotonin) are a contributing cause of the pain and dysfunction of fibromyalgia, and adequate iron is necessary for their production. The authors begin by observing:

“Iron is essential for a number of enzymes involved in neurotransmitter synthesis. Analysis of cerebrospinal fluid in fibromyalgia syndrome (FMS) has shown a reduction in the concentration of biogenic amine metabolites, including dopamine, norepinephrine and serotonin. This study aimed to investigate the association of ferritin with FMS.”

To investigate this association serum ferritin, vitamin B12 and folic acid were measured in 46 patients with primary FMS and 46 healthy controls. Their data paints a very interesting picture:

“Binary multiple logistic regression analysis…showed that having a serum ferritin level <50 ng/ml caused a 6.5-fold increased risk for FMS.”

Here’s what the authors concluded from their findings:

“Our study implicates a possible association between FM and decreased ferritin level, even for ferritin in normal [see note below] ranges. We suggest that iron as a cofactor in serotonin and dopamine production may have a role in the etiology of FMS.”

Important: there is earlier research that validates 50 ng/ml as the correct low point for serum ferritin, but many labs have not caught up and still have a report with a reference range for ferritin that is too low. This is a key point in clinical practice.

Iron supplementation can cause a zinc deficiency—implications for anger and depression

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British Journal of NutritionEven borderline anemia due to mild iron deficiency has profound effects. But as this study recently published in the British Journal of Nutrition reveals, care must be taken to avoid creating a functional zinc deficiency even when iron supplementation is necessary. The authors begin by observing…

“Interventions to combat mild Fe deficiency in women of childbearing age may affect Zn nutriture.”

Three groups of subjects with low iron were randomly assigned to one of three groups: dietary advice, a daily iron supplement and placebo. Their data showed that serum zinc increased in the dietary advice group (who ate more meat) and the placebo group. In the iron supplement group zinc decreased, leading to their conclusion:

“Zn status was not improved compared with placebo by an Fe-based dietary intervention. However, a daily moderate-dose Fe supplement with meals appeared to lower Zn status in these young adult women.”

European Journal of Clinical NutritionAmong its many functions, zinc is involved in neurotransmitter production and the regulation of mood. This important study recently published in the European Journal of Clinical Nutrition begins with the observation…

“The relation of zinc (Zn) nutriture to brain development and function has been elucidated. The purpose of this study is to examine whether Zn supplementation improves mood states in young women.”

The authors used a double-blind, randomized and placebo-controlled procedure to correlate psychological measures, somatic symptoms and serum zinc in two groups who took either a multivitamin or a multivitamin with zinc daily for 10 weeks. What did their data reveal?

“Women who took MV and Zn showed a significant reduction in anger–hostility score and depression–dejection score in the Profile of Moods State (POMS) and a significant increase in serum Zn concentration, whereas women who took only MV did not.”

The authors summarized their findings by concluding:

“Our results suggest that Zn supplementation may be effective in reducing anger and depression.”

It’s easy to see the strong biological momentum to feeling angry and/or depressed around menstruation? Iron is a necessary co-factor for both serotonin and dopamine. Supplementing iron can reduce zinc status, also an important mood-regulating co-factor. Even without adding the hormonal component it’s clear why so many women need help with this.

Fibromyalgia, iron and neurotransmitters

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European Journal of Clinical Nutrition 0310You might think that functionally low iron would contribute to the pain and fatigue of fibromyalgia through its effect on the oxygen carrying capacity of the blood, which would not be incorrect. But as this study just published in the European Journal of Clinical Nutrition reveals, there is another very important effect of suboptimal iron levels.

“Iron is essential for a number of enzymes involved in neurotransmitter synthesis. Analysis of cerebrospinal fluid in fibromyalgia syndrome (FMS) has shown a reduction in the concentration of biogenic amine metabolites, including dopamine, norepinephrine and serotonin. This study aimed to investigate the association of ferritin with FMS.”

Ferritin, a protein that stores iron, is the most accurate single quantifier for iron stores in the body. Adequate iron is mandatory for the production of neurotransmitters including dopamine and serotonin (one of the reasons why depression occur around the time of menses). What did their data show?

“…having a serum ferritin level <50 ng/ml caused a 6.5-fold increased risk for FMS.”

Doctors (and everyone), notice the serum ferritin level. Many practitioners are not aware of other research showing that the common laboratory reference ranges for ferritin are too low and that 50 ng/ml should be the cut-off point. Additionally, there are a number of mechanisms by which suboptimal dopamine and/or serotonin production can affect the experience of pain and fatigue with FMS.

The authors’ conclusion is consonant with the existing evidence:

“Our study implicates a possible association between FM and decreased ferritin level, even for ferritin in “normal” ranges [quotation marks added]. We suggest that iron as a cofactor in serotonin and dopamine production may have a role in the etiology of FMS.”

If there is a question about iron, have your serum ferritin checked (at least) and make sure that it is not lower than 50 ng/ml.