January 2019 – Vol. 13, Issue 01

 In This Issue…                                                                            

  • This supplement may restore damaged gut in patients with IBS
  • Vitamin B1’s role in critical illness gains attention
  • DHA improves lipoprotein metabolism more than EPA
  • Review says Vitamin D supplements do not prevent fractures, but is there more to the story?
  • Study finds functional vitamin D deficiency in pregnancy more clinically relevant than serum vitamin D 


CLINICAL UPDATE – This supplement may restore damaged gut in patients with IBS  
            In this randomized, placebo-controlled trial, 106 patients were studied, all of whom were experiencing diarrhea  and irritable bowel symptoms following a recent enteric infection (infection in the small intestine).  In addition, all patients had intestinal hyperpermeability (“leaky gut”) at the beginning of the trial, which was confirmed with a urinary diagnostic test for intestinal wall integrity. The patients were divided into two groups – one group (n=52) was given placebo and another group (n=54) was given 5 grams of glutamine orally three times a day, for a total of 15 grams daily – a higher than typical dose.
            After eight weeks, 80% of the group taking glutamine achieved a major reduction in irritable bowel symptoms, as quantified by a standardized scoring system, compared with only 6% of the placebo group.  Glutamine also reduced bowel movement frequency and normalized intestinal permeability, which did not happen in the placebo group.  No serious side effects were seen in the group taking glutamine.
            Glutamine is the most predominant amino acid in the body and is especially utilized by the small intestine to maintain tight junctions between intestinal epithelial cells.  It is an essential micronutrient for maintaining the integrity of the gut wall, which can be seriously compromised by infections.  This amino acid is commonly used as fuel by many fast-growing cells or regenerating tissue such as the intestinal wall.  Interestingly, glutamine can be a source of fuel for tumor cells because they are also fast growing cells, suggesting that targeted supplementation to specific patients – in this case, patients with post-infection induced diarrhea – is key. 
          (Gut, August 2018)
LINK to ABSTRACT Randomised placebo-controlled trial of dietary glutamine supplements for postinfectious irritable bowel syndrome.


CLINICAL UPDATE – Vitamin B1’s role in critical illness gains attention  
            Vitamin B1, also known as thiamine, plays a very important role in metabolism as it is a cofactor for the production of energy in every cell. In times of acute metabolic stress – such as surgery, fever, infection, or sepsis – thiamine stores are often depleted in patients, especially those who are critically ill. Consequently, vitamin B1 deficiency can cause complications for such patients, manifesting clinically in various ways including neuropathy, congestive heart failure and lactic acidosis. 
           In this review, the Department of Internal Medicine at Texas Tech University Health Sciences Center states that vitamin B1 deficiency should be considered in hospitalized patients in order to reduce the likelihood of severe complications for those patients that are critically ill. This is especially relevant in the intensive care unit.  Intravenous administration of vitamin B1 to critically ill patients can correct side effects such ranging from cardiac dysfunction to delirium.
             (The American Journal of Medical Sciences, October 2018)
LINK to ABSTRACT Thiamine Deficiency: An Important Consideration in Critically Ill Patients.


CLINICAL UPDATE – DHA improves lipoprotein metabolism more than EPA
            The effect of two different omega 3 fatty acids on lipoprotein metabolism were evaluated in this study – EPA (eicosapentaenoic acid) and DHA (dococahexaenoic acid).  Both DHA and EPA are considered anti-inflammatory fatty acids that are beneficial for heart health although the differences between their effects on lipoprotein metabolism are not completely known.   This study sought to determine how each omega 3 fatty acid specifically affects the lipoprotein profile in people with abdominal obesity and subclinical inflammation. 
            154 people were included in this study (48 men, 106 women).  All participants were overweight and chronically inflamed and underwent three treatment phases:  Phase 1 was a regimen of high dose (2.7 grams daily) EPA for ten weeks.  Phase 2 was a regimen of high dose (2.7 grams daily) DHA for ten weeks.  Phase 3 was a regimen of high dose (3 grams daily) of corn oil, a known inflammatory oil.   Each phase was separated by 9 weeks of “wash-out” in order to eliminate any overlapping effects of the different treatments.
            At the end of the trial, DHA increased the size of low-density lipoproteins, meaning they were less atherogenic.  “Bigger is better” when it comes to low-density lipoprotein size, since larger, buoyant LDL particles cannot penetrate the walls of the arteries as easily as smaller LDL particles, and are thus less harmful.  In other words, DHA had a more profound effect than EPA in changing the LDL particle size to be healthier.  The mechanism of action for this clinical effect was that high-dose DHA increased LDL turnover, meaning the patients taking DHA showed an improved capacity for clearing out LDL particles.
            Interestingly, while DHA increased LDL particle size (a good effect), reduced the percentage of small LDL (a good effect), it also increased LDL cholesterol concentrations (an often misunderstood effect).  Besides the conclusion that DHA improved lipoprotein profiles more than EPA, this study also shows how lipoprotein measurement is more clinically relevant than cholesterol levels since not all lipoproteins contain the same amount of cholesterol within them.  Since small LDL lipoproteins are a main culprit in atherosclerosis, the misunderstood effect of increased serum cholesterol when lipoproteins change from small (harmful) to large (not harmful) should be known.
          (The Journal of Clinical Endocrinology and Metabolism, August 2018)
LINK to ABSTRACT High-Dose DHA Has More Profound Effects on LDL-Related Features Than High-Dose EPA: The ComparED Study.


 CLINICAL UPDATE – Review says Vitamin D supplements do not prevent fractures, but is there more to the story?
            In this meta-analysis (a compilation of data from several studies), 81 randomized controlled trials with a combined total of over 53,000 patients were evaluated.  The incidence of bone fractures, falls and bone mineral density were reviewed and compared to vitamin D supplementation at different dosages.  After the comprehensive review of all included data, the authors concluded that “vitamin D supplementation does not prevent fractures or falls, or have clinically meaningful effects on bone mineral density” further stating that “there is little justification to use vitamin D supplements to maintain or improve musculoskeletal health.”
            These conclusions notwithstanding, this paper does not explicitly deny the role of vitamin in bone health.  Past research has shown that vitamin D stimulates an important bone building protein (osteocalcin) and that a deficiency of vitamin D may pull minerals out of bone making them weaker.  However, this study is not disclaiming the role of vitamin D in bone health – rather it is disclaiming the role of vitamin D supplementation in bone health, a subtle but very important distinction.
            This paper reveals three fundamental problems in nutrient supplementation studies:  (1) several micronutrients in addition to vitamin D are needed to maintain proper bone strength such as calcium, magnesium and vitamin K; and (2) in most cases, micronutrients work together so blind supplementation of only one nutrient may yield non-impressive results; and (3) supplementation may have better clinical outcomes on patients who are actually measured by diagnostic testing to be deficient, such that supplementation is targeted to repletion of existing, diagnosed deficiencies.
          (Lancet Diabetes and Endocrinology, November 2018)
LINK to ABSTRACT Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta-analysis, and trial sequential analysis.


CLINICAL UPDATE – Study finds functional vitamin D deficiency in pregnancy more clinically relevant than serum vitamin D
            Serum vitamin D was measured in 1754 pregnant women at the beginning of their second trimester. All women included had low-risk pregnancies with only one child (no twin pregnancies included in the study).  Parathyroid hormone was also measured in all of the women, as it is sometimes considered a functional marker for vitamin D since it increases calcium absorption in the intestine by telling the body to produce more of the active form of vitamin D when blood levels of calcium are low.  A delicate biofeedback system between vitamin D, calcium and parathyroid hormone exists so that a sense of vitamin D function, notwithstanding serum levels, can occur when both serum vitamin D and parathyroid hormone are measured, according to this study.
            17% of the women had low serum vitamin D (defined as less than 30nmol/L), while 6% of the women had a functional vitamin D deficiency, which was defined by the authors as low serum vitamin D combined with increased parathyroid hormone.  Interestingly, neither low serum vitamin D nor elevated parathyroid hormone alone increased the risk of any of the measured pregnancy complications which included as blood pressure, pre-eclampsia or small for gestational age births.  However, in the women with a functional vitamin D deficiency, there was an increase in mean arterial pressure (blood pressure) and small for gestational age babies.  
          The authors conclude that the “concept of functional vitamin D deficiency, reflecting calcium metabolic stress, should be considered in studies of vitamin D in pregnancy.”  This conclusion supports the notion that functional deficiencies are more clinically relevant than static serum measurements of vitamin D.
           (American Journal of Clinical Nutrition, October 2018)
LINK to ABSTRACT Exploring the concept of functional vitamin D deficiency in pregnancy: impact of the interaction between 25-hydroxyvitamin D and parathyroid hormone on perinatal outcomes.