February 2018 – Vol. 12, Issue 2


In This Issue…                                                                            

  • JAMA article promotes “targeted supplementation”
  • This lipid mediator gains attention as a potential biomarker for people at high risk for imminent stroke
  • Are vitamin D and calcium supplements making a difference in bone health for older people?
  • Low functional vitamin B6 increases risk of death in kidney transplant patients
  • Lymphocyte response in colon tumors is a better indicator of cancer recurrence than common genetic or pathology markers 


CLINICAL UPDATE – JAMA article promotes “targeted supplementation”
            The authors of a recent editorial on the use of vitamin and mineral supplements published by the American Medical Association do not recommend routine micronutrient supplementation for the general population.  However, in the same statement, the authors explicitly state that “targeted supplementation may be warranted in high-risk groups” which they define as people in certain life stages (pregnancy, for example) or people with specific risk factors (those on certain medications, for example).
            Further in the editorial, it is encouraged that clinicians proactively ask about supplement use in their patients.  Since micronutrient trials have shown both benefit and harm, the authors conclude that multivitamin supplementation is not recommended for generally healthy adults, citing the possible interactions as a potential reason.  But instead of dismissing all supplementation, they suggest a targeted approach is most effective and emphasize that the baseline nutrient status is a “potentially important modifier of the treatment effect.”  In other words, this editorial suggests that micronutrient supplementation recommendations should be determined by a person’s actual nutrient status versus broad recommendations to the general public.
          (Journal of the American Medical Association, February 2018)
LINK to EDITORIAL Vitamin and Mineral Supplements: What Clinicians Need to Know.

CLINICAL UPDATE – This lipid mediator gains attention as a potential biomarker for people at high risk for imminent stroke
            New research from Tulane Medical School in Louisiana looked at lipid mediators found in the circulating blood of patients that had just experienced a plaque rupture event (cholesterol buildup in their carotid artery had “broken” free, i.e. ruptured).  Blood was collected on 21 people who had just experienced this plaque rupture and compared with blood from 24 people who had similar blockages (stenosis) in their carotid artery but who did not have an acute event and were completely without symptoms.
          Levels of the heart healthy omega-3 fatty acid DHA (docosahexanenoic acid) were much lower in people who had plaque rupture.  In addition, levels of resolvinD1 (RvD1) were also much lower in people experiencing acute symptoms.  Resolvins are metabolites of the omega 3 fatty acids EPA and DHA.  (RvE = derived from EPA and RvD = derived from DHA).  As the name implies, resolvins serve to resolve the initial inflammatory response so that healing of the injured site – in this case, an artery – can begin.  In people who have plaque rupture, which is considered an injury to the lining of the blood vessel, circulating resolvinD1 and its precursor DHA are low, compared to people who have arterial blockages but have not yet experienced a plaque rupture, suggesting this pro-inflammatory profile is associated with stroke.
          (Prostaglandins, Leukotrienes and Essential Fatty Acids, October 2017)
LINK to ABSTRACT Circulating inflammation-resolving lipid mediators RvD1 and DHA are decreased in patients with acutely symptomatic carotid disease.  


CLINICAL UPDATE – Are vitamin D and calcium supplements making a difference in bone health for older people?
            A recent paper suggests the answer is no, but it’s not that simple.  Since osteoporosis-related fractures are increasing worldwide and cause major economic burdens on those affected, a group of researchers sought to review several studies done on calcium and vitamin D supplements and their effect (or lack of) on bone fractures.
            A total of 33 studies done in the five-year span between 2012 and 2017 were considered in this review, which involved over 51,000 people.  The number of hip fractures was evaluated relative to calcium supplementation, vitamin D supplementation, combined calcium + vitamin D supplementation, or placebo.  The researchers also evaluated other bone breaks, although hip fractures were the main focus of this review. Finally, all studies included only people over the age of 50 that were living independently in their communities – i.e. non-hospitalized and not living in nursing homes.
            The authors of this review concluded that the use of calcium or vitamin D supplements either alone or in combination was not associated with a lower risk of fractures among older adults when compared to placebo or no treatment.  They further opine that general guidelines to supplement calcium and/or vitamin D should not be applied to adults living independently, even though many medical institutions recommend supplemental calcium and vitamin D to prevent osteoporosis in frail or elderly patients.  Since micronutrients work synergistically, generalized recommendations on supplementation regimens may not elicit the desired effect, this analysis suggests. 
           This review further illustrates the inherent difficulty in fitting micronutrient supplementation effects into the randomized controlled trial paradigm, particularly when it comes to bone health as measured by relatively extreme endpoints – hip fracture, nonvertebral fracture, veterbral fracture and total fracture.  Several micronutrients affect bone health regardless of calcium and vitamin D status – vitamin K, magnesium and zinc, for example. In other words, targeted supplementation – i.e. correcting specific deficiencies in an individual – may be a more effective approach than generalized recommendations to an entire population.
           (Journal of the American Medical Association, December 2017)
LINK to ABSTRACT Association Between Calcium or Vitamin D Supplementation and Fracture Incidence in Community-Dwelling Older Adults: A Systematic Review and Meta-analysis.


CLINICAL UPDATE – Low functional vitamin B6 increases risk of death in kidney transplant patients
            In this study, levels of vitamin B6 – which is known to benefit the immune system and quell inflammation – were measured in 678 patients that had undergone a kidney transplant and compared to levels of vitamin B6 in 297 healthy control patients. The kidney transplant patients had been stable for at least five years when this study was done, meaning B6 status was measured on patients after they had fully recovered (versus immediately following surgery).
           In addition, both plasma vitamin B6 and functional vitamin B6 were assessed.  Vitamin B6 function was evaluated by measuring certain metabolites of tryptophan, an amino acid precursor to several neurotransmitters such as serotonin and melatonin via vitamin B6 dependent biochemical reactions.  By measuring the ratio of certain metabolites (called xanthurenic acid and 3-hydroxykynurenine), the researchers could assess not only the level of vitamin B6 found in blood, but also the functional status of vitamin B6 in the cells.  
           Once functional status of vitamin B6 was done on both the kidney transplant patients and healthy controls, they found that worse functional B6 status in the transplant patients was associated with an increased risk of mortality.  Specifically, they found that the hazard ratio of transplant patients with low B6 function was about 1.5, meaning their risk of dying from cancer or infectious disease was increased by 50% compared to those with adequate B6 function. 
           (American Journal of Clinical Nutrition, December 2017)
LINK to ABSTRACT Functional vitamin B-6 status and long-term mortality in renal transplant recipients.


CLINICAL UPDATE – Lymphocyte response in colon tumors is a better indicator of cancer recurrence than common genetic or pathology markers
            1285 patients with stage 2 or stage 3 cancer were examined for several biomarkers.  One biomarker that was measured is a type of white blood cell that leaves the bloodstream in order to infiltrate a tumor and helps fight malignant cells – called TIL, for tumor-infiltrating lymphocyte.  Another biomarker measured in each patient is called dMMR (for DNA mismatch repair) which is a system for correcting mistakes that accumulate in the genetic material through errors in DNA replication. The MMR system also repairs certain forms of DNA damage.  Finally, the presence of certain genetic mutations associated with colon cancer were recorded for each patient. 
            Although previous research suggested that the ability of the cell to repair DNA damage (called MMR biomarker in this study) is highly linked to better survival rates in colon cancer patients, the results of this study suggest that this is only part of the story.  This paper suggests that the MMR (mismatch repair) ability may be dependent on the presence of lymphocytes in the tumor, which help fight rogue cancer cells.  In other words, the system for keeping the genetic code from being “corrupted” depends on whether or not these cancer-fighting white blood cells are there to do the work.  Interestingly, the authors also conclude that the presence of these special lymphocytes indicated a better prognosis than several genetic mutations commonly linked to colon cancer.  In addition, the presence of tumor-infiltrating lymphocytes is a better indicator of disease prognosis than some tissue pathology markers, concluding that lymphocyte response in colorectal cancer is important to prognosis and should be clinically reported.
           (Gut, January 2018)
LINK to ABSTRACT Lymphocytic response to tumour and deficient DNA mismatch repair identify subtypes of stage II/III colorectal cancer associated with patient outcomes.