June 2018 – Vol. 12, Issue 6

In This Issue…                                                                            

  • Case Report: High dose vitamin B1 clears up 26 years of painful headaches
  • Vitamin B3 may lower a dangerous type of lipoprotein
  • Diagnosis of amino acid deficiency diseases gain attention
  • High dose vitamin C kills liver cancer cells, according to study
  • Use of this common biomarker may overestimate B12 deficiency in certain patients



CLINICAL UPDATE – Case Report:  High dose vitamin B1 clears up 26 years of painful headaches
            In this case report, a 41-year-old man who had been suffering from cluster headache since the age of 15 years old was treated with high dose vitamin B1 (thiamine).  He had been diagnosed with cluster headache at a neurological center in Italy. His first headache occurred at age 15 shortly after a motorcycle accident and they increased in frequency over the years, with acute pain and intensity that significantly compromised his quality of life.  Although the patient would experience some headache free months over the years, in January 2016 the headache clusters began occurring daily with no pain-free period for an entire year.  The patient had been treated with sumatriptan, a commonly prescribed drug for cluster headache, which did not work.  He had also been prescribed prednisone, although this not alleviate the pain either.  In December 2016, he was given oral high dose vitamin B1.  Initially, the dose was 250mg, then it was increased to 750 mg after a few days.  Within 10 days, the headache pain disappeared.  He continued the vitamin B1 daily indefinitely.
            Interestingly, the neurological center requested that he stop the vitamin B1 in order to test whether the headaches would come back.  He refused this request citing his reluctance to re-experience his headache pain.  However, in May 2017 (five months after B1 treatment started), the patient forgot his vitamin B1 while on a vacation.  Within 48 hours of the last dose, a painful headache occurred.   He resumed vitamin B1 therapy after his vacation and was able to reduce the dose to 500mg with no recurrence of headaches to date.
           Cluster headache is a painful condition in which very severe headaches occur with little warning and in “clusters” meaning several headaches will occur in a short time period.  Patients of cluster headache have very little or no warning when they occur unlike migraine which may gradually build in intensity.  Classified as a neurological condition, cluster headache is characterized by very severe and intense pain around the eye, often on only one side of the head.  Some researchers suggest that the role vitamin B1 plays in energy metabolism, brain function and pain modulation make it a potential therapy for this rare neurological disorder. 
           (Case Reports in Neurological Medicine, April 2018)
LINK to ABSTRACT Oral High-Dose Thiamine Improves the Symptoms of Chronic Cluster Headache.
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CLINICAL UPDATE – Vitamin B3 may lower a dangerous type of lipoprotein
             In a large clinical study called AIM-HIGH (for Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes), researchers evaluated the impact of extended release niacin (vitamin B3) on blood lipids.  In a previous review of patients in this AIM-HIGH trial, niacin showed no benefit to statin-treated patients when analyzed as a whole group.  However, in a subsequent analysis, niacin appeared to benefit patients who had high triglycerides (over 200 mg/dL) and very low HDL (less than 32 mg/dL).  In this analysis, the authors sought to find out the specific changes in lipoproteins that conferred the benefit seen in the subset of patients with high triglycerides and low HDL.
            Lipoprotein particles were analyzed on 2457 participants in the AIM-HIGH trial to establish baseline values and again after one year of treatment with extended release niacin.  Those taking niacin had higher HDL after one year (a good outcome since HDL is protective).  In addition, the analysis of lipoprotein subfractions showed that this benefit – specific to people with high triglycerides and low HDL – was likely due to the reduction in remnant lipoproteins, also known as RLP.
           This unique lipoprotein is particularly harmful because unlike LDL particles, which have to undergo oxidation before they can be taken into the arterial intima, RLP lipoproteins can be readily transformed into foam cells which is what comprises arterial plaque.  In fact, RLP is one of the four major risk factors cited by the National Cholesterol Education Program that contribute to heart disease.   This paper suggests that the benefit seen in patients taking niacin was due to a reduction in this particularly harmful lipoprotein called RLP.
          (Journal of Clinical Lipidology, May 2018)
LINK to ABSTRACT Relationship between lipoprotein subfraction cholesterol and residual risk for cardiovascular outcomes: A post hoc analysis of the AIM-HIGH trial.


CLINICAL UPDATE – Diagnosis of amino acid deficiency diseases gain attention
             In this review, the challenges with diagnosis of diseases caused by defects in amino acid synthesis are evaluated.  Specifically, deficiency diseases of four amino acids – serine, glutamine, proline and asparagine – are thoroughly reviewed.  The authors explain that, unlike commonly recognized inborn errors of metabolism that cause elevated levels of metabolites that are easily detected in blood or urine, diseases caused by defects in amino acid synthesis do no cause a rise in metabolites that can be quantified via diagnostic testing. In fact, the authors emphasize that amino acid synthesis defects may cause low (not high) values of metabolites or even completely normal levels, making diagnosis particularly difficult.
            However, the authors point out that although the four amino acid synthesis defects are in seemingly unrelated metabolic pathways, they tend to have clinical similarities, namely neurological manifestations such as seizures, mental disabilities or microcephaly (smaller than normal head size in infancy).  The authors state that in many cases of amino acid deficiency defects, the plasma or cerebral spinal fluid are “non-informative” posing a real diagnostic challenge. For example, in serine deficiency diseases, they state that “analysis of urine amino acids to diagnose serine deficiency is not helpful because, for still unclear reasons, amino acid excretion is normal in patients.”  Interestingly, in glutamine synthesis deficiency, the authors note that the synthesis defect was manifested in lymphocytes.  Finally, the authors further explain similar diagnostic challenges in asparagine deficiency.
            The authors of this review conclude that a paradigm shift in how inborn errors of metabolism are diagnosed is happening, “requiring further development of functional assays for these amino acid disorders.”
            (Journal of Inherited Metabolic Disorders, 2017)
LINK to ABSTRACT Amino acid synthesis deficiencies.
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CLINICAL UPDATE – High dose vitamin C kills liver cancer cells, according to study
             A Liver Cancer Center in Shanghai, China investigated the effect of pharmacological doses of vitamin C on liver cancer cells in a recent study.  High vitamin C concentrations (given intravenously) induced cell death in liver cancer cells, in particularly liver cancer stem cells. In 613 liver cancer patients who had had a liver resection (part of the liver removed), retrospective data showed that the administration of intranvenous vitamin C was linked to improved prognosis.
          The key protein needed to actively import vitamin C into a cell called SVCT-2 (sodium dependent vitamin C transporter 2) was highly expressed in liver cancer stem cells.  This means that the high doses of vitamin C were preferentially taken up by the liver cancer stem cells, which actually increased intracellular oxidative stress in these cells by altering the oxidative balance, creating DNA damage and ultimately causing cell death. As a result, high doses of vitamin C impaired tumor growth and eradicated liver cancer stem cells.  The authors suggest that vitamin C may be a “novel therapeutic strategy” for liver cancer treatment.
            (Nature Partner Journals Precision Oncology, January 2018)
LINK to ABSTRACT Vitamin C preferentially kills cancer stem cells in hepatocellular carcinoma via SVCT-2. 
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CLINICAL UPDATE – Use of this common biomarker may overestimate B12 deficiency in certain patients
            It is well established in medical literature that people who have vitamin B12 levels that fall within the “normal” range for serum may actually have a functional B12 deficiency.  A functional B12 deficiency is typically diagnosed via elevated levels of a metabolite in urine called MMA, also known as methylmalonic acid.  In this study, researchers found that impaired kidney function (as indicated by glomerular filtration rate) can also result in higher levels of MMA in urine, therefore complicating the diagnosis of B12 deficiency.
            The researchers collected data on 2906 patients for vitamin B12 concentrations in blood, kidney function and the metabolite MMA. They concluded that if they had not adjusted for kidney function when assessing MMA levels in urine, B12 deficiency was overestimated by 40% (in contrast to underestimation of B12 deficiency when only looking at serum levels compared to MMA).  Especially in the elderly, impaired GFR (kidney function) may make diagnosis of B12 deficiency via urine levels of MMA less accurate, according to this research. 
            (Annals of Clinical Biochemistry, January 2018)
LINK to ABSTRACT Improved testing for vitamin B12 deficiency: correcting MMA for eGFR reduces the number of patients classified as vitamin B12 deficient.