JANUARY 2018 – Vol. 12, Issue 1

In This Issue…                                                                            

  • An unhealthy diet programs immune cells to be “hyperactive”
  • Vitamin C may improve blood sugar control in diabetics
  • Vitamin B2 protects heart tissue after an attack via by turning on protective genes
  • Babies born to women with low vitamin D are twice as likely to have heart defects
  • Both too much and too little HDL is linked to higher risk of infection


CLINICAL UPDATE – An unhealthy diet programs immune cells to be “hyperactive”
            Epigenetics – the study of changes in organisms caused by modification of gene expression rather than alteration in the genetic code itself– has gained much attention in recent years.  Environmental factors including diet, smoking and stress have been shown to impact gene expression through epigenetic mechanisms.
            In a recent experiment involving the collaboration of several medical institutions, an experiment was performed on mice to determine how their immunity responded to a typical Western diet.  When mice were fed a Western diet, systemic inflammation occurred which was entirely expected. However, what was particularly interesting was that the Western (inflammatory) diet fundamentally changed their immune system.  After eating high calorie, low nutrient food, not only did the mice exhibit more systemic inflammation (not surprising), but their white blood cells became programmed to remain hyper-sensitive to inflammatory triggers.  The cellular “memory” had changed.
            Here is how it worked: a gene called NLRP3 (for Nucleotide binding domain Like Receptor Protein) makes a protein that is used by our immune cells to recognize harmful bacteria and viruses.  This protein made by the NLRP3 gene recognizes “bad” cell remnants.  These can be parts of bacterial cell membranes, or pieces of genetic material found in viruses, or even parts of a cell that are supposed to be contained but may leak out due to cellular trauma.  It is a fundamental way our immune cells recognize something is wrong – bacteria are present or acute tissue damage occurred, for example – and thus launch an inflammatory response to deal with the biological crisis and take care of it.
            In this study, the immune cells in mice fed a typical Western diet of high-calorie, low nutrient foods launched the same inflammatory response as if an invading bacterial infection were present. Furthermore, the immune cells became hypersensitive so that they continued their inflammatory attack, even when the mice’s diet was returned to normal. In other words, the immune cells responded to a Western diet in the same way it responds to infections.  But instead of the infection clearing up, the Western diet seemed to reprogram the immune cells to stay in a perpetual hyperactive state. These results may help explain why chronic inflammation is behind so many lifestyle-related diseases such as heart disease, obesity and diabetes.
          (Cell, January 2018)
LINK to ABSTRACT Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming. 


 CLINICAL UPDATE – Vitamin C may improve blood sugar control in diabetics
            In this meta-analysis and review of 22 studies that included 937 patients, the relationship between vitamin C and three markers of blood sugar control were analyzed.  When all studies were reviewed together, there was no link between vitamin C and blood glucose (short term measure of blood sugar), hemoglobin A1c (long term measure of blood sugar) or insulin. 
          However, when looking at people with type 2 diabetes, vitamin C did have a beneficial effect on insulin levels, when supplemented for at least 30 days.  Further analysis showed that the effect vitamin C had on insulin levels was directly dependent on how much average blood sugar was present when the supplementation began.  In other words, the more severe the dysglycemia, the more effective vitamin C supplementation was in improving it.  Such data reinforces the notion that personalized interventions may be more effective than the one-size-fits-all approach to supplementation regimens.
          (European Journal of Clinical Nutrition, December 2017)
LINK to ABSTRACT Effects of vitamin C supplementation on glycaemic control: a systematic review and meta-analysis of randomised controlled trials.

CLINICAL UPDATE – Vitamin B2 protects heart tissue after an attack via by turning on protective genes
            The role of vitamin B2, also called riboflavin, on protecting heart tissue was investigated by a group of researchers in China.  To do this, they treated mice with vitamin B2 and subsequently induced a heart attack (myocardial infarction) and then measured the activity of a specific B2-dependent protein.  This protein called LSD1 (lysine specific histone demethylase 1) is synthesized when its corresponding gene is activated, and it then activates two other genes that control phospholipid synthesis.  Phospholipids, which make up cell membranes, play an important role in protecting biological tissue from hypoxic injury (damage due to lack of oxygen). These scientists demonstrated that giving vitamin B2 to mice undergoing a heart attack actually turned on genes that then turned on other genes that protect the heart. 
          It is known that low B2 can impair certain metabolic pathways known as methylation reactions.  Methylation is a process by which things like DNA or proteins are chemically modified so their function is also modified.  Vitamin B2 is a key cofactor in methylation reactions. Vitamin B2 decreased the injury to the heart tissue by activating a gene involved in methylation. This study demonstrates how this vitamin can very specifically affect genetic expression – via its role in methylation – in ways that are cardioprotective.  Conversely, deficiency in vitamin cofactors may have detrimental effects.
          (Journal of Molecular and Cellular Cardiology, January 2018)
LINK to ABSTRACT Riboflavin attenuates myocardial injury via LSD1-mediated crosstalk between phospholipid metabolism and histone methylation in mice with experimental myocardial infarction.


CLINICAL UPDATE – Babies born to women with low vitamin D are twice as likely to have heart defects
            In this case-control study done in The Netherlands, two groups of women were compared:  345 mothers of a child born with a congenital heart defect and 432 mothers of children that did not have any heart problems. Vitamin D was measured in the blood of all the mothers and categorized as deficient (less than 50nmol/l), moderate (50-75 nmol/l) or adequate (greater than 75 nmol/l).  Only 27% of mothers with children having a heart defect had adequate vitamin D status while 38% of mothers with healthy children had adequate vitamin D.  Mothers with moderate vitamin D status (as quantified by ranges listed above) were 1 ½ times more likely to have a child with a congenital heart defect.  If the mother fell into the deficient vitamin D category, they were twice as likely to have a child with a congenital heart defect.  Although a case-control study such as this certainly does not prove causality, it is worth noting that low vitamin D in pregnant women is linked to higher rates babies with heart defects.
         (Early Human Development, December 2017)
LINK to ABSTRACT A compromised maternal vitamin D status is associated with congenital heart defects in offspring.


CLINICAL UPDATE – Both too much and too little HDL is linked to higher risk of infection
            There is some evidence that high density lipoprotein (HDL) – the lipoprotein that is commonly regarded as heart protective and beneficial – may play an important role in our immune system.  To test whether high or low HDL is linked to infections, a group of Danish researchers evaluated the infection rate of over 100,000 individuals and compared it to their HDL cholesterol levels.   Two studies were included in this analysis: (1) an evaluation of 97,166 patients in the Copenhagen General Population Study and (2) a review of 9387 patients in the Copenhagen City Heart Study. 
           Using 20 years of hospital records, the HDL cholesterol of any person who had an infection severe enough to require hospitalization was recorded.  A U-shaped association between HDL cholesterol and the risk of infections was seen.  Stated differently, a person with very low HDL cholesterol or very high HDL cholesterol were both at an increased risk for infections.
           Although the authors specifically state in their conclusion that this relationship is not necessarily indicative of causality, it does suggest how HDL is sometimes misunderstood.  In the past, HDL was often seen primarily as a beneficial lipid in which “more was better”.  However, in recent years, emerging evidence, such as this paper, suggests that there may be an optimal amount of HDL and too little or too much can both be problematic. 
          (European Heart Journal, December 2017)
LINK to ABSTRACT U-shaped relationship of HDL and risk of infectious disease: two prospective population-based cohort studies.