February 2019 – Vol. 13, Issue 02

 In This Issue…                                                                            

  • Researchers suggest breast cancer patients should proceed with caution when taking antioxidant supplements during treatment
  • Oral supplementation of this powerful antioxidant reduces tissue damage from electrical burn injury
  • Study suggests that when mothers take choline, their babies have improved cognition
  • Is drug re-purposing going to become the new normal in psychiatric drug development?
  • CASE REPORT: Chronic zinc supplementation causes anemia by inducing copper deficiency


CLINICAL UPDATE – Researchers suggest breast cancer patients should proceed with caution when taking antioxidant supplements during treatment
            A group of researchers from Germany collected data from over 2000 postmenopausal women who had been diagnosed with breast cancer.   The data were on patients that were formerly involved in a study called MARIE (Mamma Carcinoma Risk Factor Investigation), which was conducted from 2002-2005 in Germany with the purpose of identifying potential risk factors for the development of breast cancer after menopause.
            During the initial MARIE study, women diagnosed with breast cancer were interviewed, among other things, about their use of dietary supplements including, but not limited to, antioxidant supplements. Several years later in 2009 and 2015, the women were interviewed again about supplement use and the results were compared to rates of breast cancer recurrence.
            The authors concluded that the women who took antioxidant supplements during chemotherapy or radiation treatment had an increased risk of total mortality and breast cancer recurrence. Interestingly, there was no association between supplement use and prognosis in women who simply took supplements after they were diagnosed, but not necessarily during treatment.
            This raises a question of why antioxidant supplements, particularly when they are taken during chemotherapy or radiation, were linked with a worse prognosis. Some studies have suggested antioxidants can mitigate the side effects of chemotherapy, but it should be understood that antioxidants via supplementation can potentially induce a pro-oxidant effect.   Further, whether this pro-oxidant effect occurs in healthy or cancerous cells represents another complicating factor on assessing the value of antioxidant supplements in certain populations.
            Additional factors make interpretation difficult. For example: (1) baseline levels were unknown, (2) dosages varied among antioxidants, (3) duration of supplement use, (4) consistency in taking supplements, (5) not all antioxidants behave the same in the body, and (6) and the very pertinent fact that hundreds of antioxidants exist in supplement form – some may help, some may harm.   This suggests that blind supplementation, especially during cancer treatment, may carry with it unknown risks. Targeted supplementation intended to replete actual diagnosed nutrient deficiencies may be a more pragmatic approach.
           (American Journal of Clinical Nutrition, January 2019)
LINK to ABSTRACT Antioxidant supplementation and breast cancer prognosis in postmenopausal women undergoing chemotherapy and radiation therapy.


CLINICAL UPDATE – Oral supplementation of this powerful antioxidant reduces tissue damage from electrical burn injury
            In burn victims, the cascade of acute damage that continues to destroy tissue even after the burn event has stopped is an important area of research. In this animal study, researchers divided 36 albino rats into two groups, both of which were exposed to a severe electrical burn injury. Group A received oral supplementation of N-acetylcysteine (NAC) for a week and Group B did not receive any supplementation. After a week, the extent of tissue damage was quantified. In addition, blood samples were obtained to assess serum levels of an enzyme indicative of severe muscle damage (creatine kinase).
            After 7 days, the necrotic area (dead tissue as a direct result of burn injury) of supplemented group was less than a third of the size of the necrotic area of the non-supplemented group.   Serum Levels of the biomarker for muscle damage were also lower in the supplemented group. N-acetylcysteine is the precursor and rate-limiting factor in the production of the uber-powerful antioxidant glutathione, which may explain some of the protective effect it demonstrated on acute burn injury seen in this study and suggests that NAC may have a beneficial effect in treatment of electrical burns.
           (Burns, December 2018)
LINK to ABSTRACT The effect of oral N-acetylcysteine on prevention of extensive tissue destruction in electrical burn injury.


CLINICAL UPDATE – Study suggests that when mothers take choline, their babies have improved cognition
            Human studies have been inconsistent on the effects of supplemental choline – a relative of the B vitamin family that is associated with brain function – by a woman during pregnancy and its effect on the cognitive abilities of her babies. Unlike animal studies, human ingestion of nutrients is inherently difficult to quantify simply because we eat what we want to eat, while animals’ diets can be strictly controlled.  
            In this study, researchers diligently tried to control – with as much precision as possible – the amount of choline ingested by pregnant women during their third trimester. The women were randomly chosen to consume either 480mg per day or 930 mg per day of choline until delivery. Their babies were evaluated for cognitive ability (information processing speed and visuospatial memory, i.e.reaction time) four times in their first year of life – at 4 months, 7 months, 10 months and 13 months.
            Reaction time was faster in babies whose moms took the higher dose of choline during pregnancy, which was approximately twice the standard recommended amount for pregnant women. In addition, the longer the duration the mother took choline during pregnancy, the more her baby seemed to benefit (infants exposed longer showed faster reaction times), leading the researchers to conclude that “even modest increases in maternal choline intake during pregnancy may produce cognitive benefits for offspring.”
           (Federation of American Societies for Experimental Biology, April 2018)
LINK to ABSTRACT Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double-blind, controlled feeding study.


 CLINICAL UPDATE – Is drug re-purposing going to become the new normal in psychiatric drug development?
            A group of Swedish researchers reviewed data on more than 142,000 mentally ill patients who had been diagnosed with either schizophrenia, bipolar disorder or psychosis between 2005 and 2016.   They compared the rates of psychiatric hospitalizations and documented self-harm in these patients with the simultaneous use of three widely prescribed non-psychiatric medications – statins (for heart disease), calcium channel antagonists (for blood pressure) and biguanides (e.g metformin for diabetes).
            All three commonly prescribed drugs were associated with reduced rates of psychiatric hospitalization. In other words, the patients taking one of the above referenced medications were admitted to hospitals for psychiatric reasons less often than those not taking the medications. The authors of the study conclude that exposure to these non-psych drugs “might lead to improved outcomes for individuals with serious mental illness.” They go on to suggest these common medications might be effective “repurposed agents for psychiatric symptoms.”
            Although potential mechanisms of action remain elusive, the notion of drug repurposing may be particularly appealing to stakeholders who benefit from already completed clinical trials, notwithstanding the clinical data in their approval and intended use is based on non-psychiatric outcomes. Although the outcomes in this analysis – psychiatric hospitalization and taking commonly prescribed drugs – are correlated, they are not meant to imply causation. Stately differently, a correlation between variables does not necessarily mean that a change in one causes a change in the other. In this study, a correlation exists but causation is far from established – an important distinction to consider as drug repurposing becomes more accepted.
            (Journal of the American Medical Association Psychiatry, January 2019)
LINK to ABSTRACT Association of Hydroxylmethyl Glutaryl Coenzyme A Reductase Inhibitors, L-Type Calcium Channel Antagonists, and Biguanides With Rates of Psychiatric Hospitalization and Self-Harm in Individuals With Serious Mental Illness.


CLINICAL UPDATE – CASE REPORT: Chronic zinc supplementation causes anemia by inducing copper deficiency
              In this interesting case report, a 27 year old quadripalegic male with a history of traumatic brain injury and chronic respiratory failure presented to the emergency department for shortness of breath. He had been on a home ventilator. Once admitted, he was given nutrition via a tube inserted directly into the stomach through the abdominal wall. His blood pressure was extremely low and bloodwork showed severe anemia. Specifically, the patient had leukopenia and neutropenia – both deficiencies of white blood cells that greatly increase the risk of infection.
           Further bloodwork showed no evidence of vitamin deficiencies commonly seen in severe anemia cases, namely vitamin B12 and folate. It was discovered that part of his wound care regimen included zinc supplementation, which had been given chronically and long-term. Consequently, his copper levels were low because a zinc-induced copper deficiency had developed. Zinc and copper work in balance and when exogenous zinc is not balanced with copper, a supplementation-induced copper deficiency will often occur over time.
            The zinc supplements were stopped and the patient was given supplemental copper to correct the imbalance. After three months, the anemia and deficiency in white blood cells was fully resolved. This case illustrates that micronutrient deficiency is a potential, and often easily correctible, cause of anemia, particularly in cases where deficiency is caused by blind supplementation of one nutrient that has the potential to induce deficiency in another, especially in high-risk populations.
            (Cureus, November 2018)
LINK to ABSTRACT A Unique Case of Severe Anemia Secondary to Copper Deficiency in an Adult Patient.
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