Methylmalonic Acid as a Biomarker of Vitamin B12

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A recent case study (L Jimenez et al. J Pediatr 2018; 192: 259-61) showed that methylamalonic acid (MMA) can be elevated in the absence of vitamin B12 deficiency.

Background:

  • Risk factors for vitamin B12 deficiency: terminal ileal resection and gastric acid blockade
  • Manifestations of vitamin B12 deficiency: megaloblastic anemia, bone marrow failure, demyelinating diseases, thrombosis, and psychiatric symptoms
  • Early assessment of vitamin B12 deficiency can be aided by MMA levels and homocysteine levels both of which are metabolized via vitamin B12-dependent pathways and are elevated in vitamin B12 deficiency.
  • MMA levels have higher sensitivity for vitamin B12 deficiency than vitamin B12 levels alone.

Key findings of this report:

  • In three children with short bowel syndrome, MMA levels were persistently elevated despite vitamin B12 supplementation and without other evidence of vitamin B12 deficiency
  • MMA levels declined after treatment of bacterial overgrowth
  • “It is hypothesized that propionate, a precursor to MMA, produced by excessive gut fermentation, is responsible for the elevation in plasma MMA levels.”

My take: this study is a good reminder of how MMA is useful in detecting vitamin B12 deficiency and points out that bacterial overgrowth may be an alternative explanation for elevated MMA levels.

Related blog posts:

Resources for Short Bowel Syndrome:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

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NY Times: Humira’s Best-Selling Drug Formula: Start at a High Price. Go Higher.

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NY Times: Humira’s Best-Selling Drug Formula: Start at a High Price. Go Higher.

An excerpt:

Humira is the best-selling prescription drug in the world…The price of Humira, an anti-inflammatory drug dispensed in an injectable pen, has risen from about $19,000 a year in 2012, to more than $38,000 today, per patient, after rebates, according to SSR Health, a research firm. That’s an increase of 100 percent…

How much you actually pay out of pocket, and whether you can afford Humira at all, depend on your insurance and eligibility for discounts…

Humira, which accounted for nearly two-thirds of AbbVie’s $25.6 billion in revenue in 2016, was not simple to develop. It is among a new class of drugs known as biologics, which are made from living cells rather than synthetic chemicals…

Looking at the international picture tells its own story about drug costs. A prefilled carton with two syringes costs $2,669 in the United States, compared with $1,362 in Britain, $822 in Switzerland and $552 in South Africa…

An analysis by the Institute for Clinical and Economic Review found that Humira’s list price would need to be discounted by at least 55 percent to be cost effective for rheumatoid arthritis, its originally approved use.

Dr. Steven D. Pearson, the founder of the institute, which provides cost benefit data to health plans, said competing drugs were overpriced as well.

“Even in a space like this, where there is a lot of competition, we don’t see the prices coming down,” he said. “That speaks to the fact that it doesn’t often function like a free market usually would.”..

AbbVie joined a few of its rivals in saying it would limit price increases to single digits this year, and so only raised Humira by another 9.7 percent this month, roughly four and a half times the inflation rate. For the drug industry, that counts as generosity.

My take: Humira is a very important and effective medication, particularly for inflammatory bowel disease and rheumatoid arthritis. I infer from this article which compares the Humira pricing strategy to that used by Martin Shkreli that if U.S. consumers are to have more affordable pharmaceuticals, government intervention will be needed. AbbVie, like many other pharmaceutical companies, will continue to aggressively price Humira; after all, 8 billion in profits is not as good as 10 billion.

Related blog posts:

Another Study: Low FODMAPs Diet for Irritable Bowel Syndrome

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Another good study on the low FODMAPs diet for irritable bowel syndrome with diarrhea (IBS-D): S Eswaran et al. Clin Gastroenterol Hepatol 2017; 15: 1890-9

This was a propspective, single-blind trial of 92 patients (84 completed study) with IBS-D (65 women) comparing the low FODMAPs diet to a modified diet recommended by the National Institute for Health and Care Excellence (NICE) for 4 weeks. Key findings:

  • The low FODMAPs group had larger increase in IBS-QOL score (15.0 vs 5.0).  In addition, based on IBS-QOL a meaningful clinical response occurred in 52% compared with 21% in the mNICE group.
  • Activity impairment was significantly reduced in the low FODMAPs group; -22.89 compared with -9.44.  Anxiety scores decreased as well.

My take: This study indicates that the low FODMAPs diet helps patient with IBS-D, and not just with their GI symptoms.

Related blog posts:

Cabin at Phantom Ranch, Grand Canyon

Mailbag for postcards (delivered via mule)

Phantom ranch canteen

Deprescribing Initiative

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A recent article (Gastroenterol & Endoscopy News, October 2017; 64-66) described an effort to reduce the problem of “polypharmacy.”  While this is clearly a problem for adult medicine, increasingly, this is an issue with pediatrics as well.

Key points:

  • In 2015, 35.8% of adults were taking at least 5 medications (JAMA 2016; 176: 473-82)
  • More medications increase the risk of adverse events, drug interactions, and costs
  • The deprescribing initiative (http://deprescribing.org/) encourages active review of medications and removing those with questionable risk-benefit trade-off
  • If stopping medicines, generally remove one at a time

 

Silymarin for Nonalcoholic Steatohepatitis

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A recent study (CW Kheong et al. Clin Gastroenterol Hepatol 2017; 15: 1940-9) examined the use of silymarin (milk thistle) in a randomized, placebo-controlled, double-blind trial for nonalcoholic steatohepatitis (NASH). Patients (n=49) who were assigned to silymarin received 700 mg three times a day for 48 weeks; there were 50 patients assigned to placebo..

Key findings: 

  • Silymarin did not significantly improve the primary outcome of achieving a lower NAS score by 30% or more; this occurred in 32.7% of the silymarin group vs. 26.0% in the placebo group.
  • Reduction in fibrosis was noted in the silymarin group (histology drop by 1 point or more): 22.4% compared to 6.0% in the placebo group.

Silymarin has many potential beneficial properties: anti-oxidant, anti-inflammatory, anti-fibrotic, anti-viral, and metabolic functions.

My take: Given the safety of silymarin, if these findings can be confirmed in a larger trial, it would be an exciting advance in the field of fatty liver disease which has no proven pharmacologic therapies.

Related blog post:

 

Grand Canyon Basin

Why Stomach Pain Improves in the Summer

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A recent small study (published online: KL Pollard et al. JPGN  doi: 10.1097/MPG.0000000000001886) indicates that the well-recognized phenomenon of improvement in functional abdominal pain during the summer months is associated with lower anxiety.  Here is a link to abstract: Seasonal Association of Pediatric Functional Abdominal Pain Disorders and Anxiety

Excerpt:

Results:

In a sample of 34 participants who completed both questionnaires, 22 reported improvements during the summer months. These participants reported a significantly higher seasonal decrease in anxiety than participants whose children’s symptoms did not improve from spring to summer (mean decrease 2.21 vs 0.08, P = 0.017). Both groups reported equal improvements in sleep and decreased stress from spring to summer. Neither group experienced statistically significant seasonal change in physical activity or fruit, vegetables, dairy, or caffeine consumption.

Conclusions:

This study suggests that amelioration of gastrointestinal symptoms in pediatric patients with AP-FGID during summer months is associated with amelioration of anxiety in the same time period. It is not yet clear whether decreased anxiety is the cause or effect of decreased AP-FGID symptom

Related blog posts:

 

Deaths and Morbidity from Childbirth –U.S. with Highest Rate in the Industrialized World

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Previously the issue of maternal mortality has been discussed on this blog: Take Two: Mushroom poisoning and maternal death with childbirth

An update on this topic from NPR: Full Link  Nearly Dying In Childbirth: Why Preventable Complications Are Growing In U.S.

For the past year, ProPublica and NPR have been examining why the U.S. has the highest rate of maternal mortality in the industrialized world. That relative high rate of death, though, has overshadowed the far more pervasive problem that experts call “severe maternal morbidity.” 

Each year in the U.S., 700 to 900 women die related to pregnancy and childbirth. But for each of those women who die, up to 70 suffer hemorrhages, organ failure or other significant complications. That amounts to more than 1 percent of all births. The annual cost of these near deaths to women, their families, taxpayers and the health care system runs into billions of dollars

In the News …Hepatitis A Outbreak in California Linked to Homelessness

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From NEJM: Full Link: Hepatitis A Outbreak in California — Addressing the Root Cause

On October 13, 2017, Governor Jerry Brown of California declared a state of emergency in response to a hepatitis A outbreak that began in the homeless population in San Diego. In the past year, more than 649 people throughout California have been infected, 417 have been hospitalized, and 21 have died from hepatitis A, making this the largest outbreak in the United States in the past 20 years. The vast majority of those affected have been homeless. Like two thirds of people who experience homelessness in California, most were unsheltered.

The environmental conditions associated with homelessness — overcrowding in encampments and emergency shelters, exposure to the elements, and limited access to facilities for hygiene and food preparation and storage — facilitate infectious-disease transmission..Infectious diseases are one of many health threats faced by homeless people. Poorly controlled chronic diseases, complications of substance use disorders and smoking, and unintentional injuries and violence are prevalent, difficult to manage, and often severe among homeless adults.

Last Year’s Most Popular Posts

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I want to thank the many people who have helped me with this blog –now with 2180 posts over more than 6 years.  This includes my wife, my colleagues at GICareforKids, and colleagues from across the country who have provided critical feedback as well as useful publications to review.  I hope this blog continues to be a useful resource.

Here are the top dozen most popular blog posts from 2017: