Dr. Ron’s Research Review – September 29, 2010

This week’s research review contains two articles on INR and Warfarin; two recent articles showing that choline and betaine reduce inflammation; and an article on folate to protect and repair DNA.

INR and Warfarin

There was no significant difference in CAM use or consumption of vitamin K-rich foods between patients with and without INRs greater than 4 or for patients with and without INRs less than 2. (Leung, Shalansky et al. 2009)

The use of CAM by patients receiving warfarin is common, and consumption of coenzyme Q(10) or ginger appears to increase the risk of bleeding in this population.  (Shalansky, Lynd et al. 2007)

Choline and Betaine

A recent study found that higher dietary intakes of choline and betaine in the Greek population reduce inflammation. It has been proposed that these nutrients are increased in the Mediterranean diet. (Detopoulou, Panagiotakos et al. 2008) (Zeisel 2008)

Folate and DNA

Folates maintain DNA stability through their ability to donate one-carbon units for cellular metabolism. Suboptimal folate status in humans is widespread. Folate maintains genomic stability by regulating DNA biosynthesis, repair and methylation. Folate deficiency induces and accelerates carcinogenesis by perturbing each of these processes. (Duthie 2010)

In the news

FDA approves the first pill to treat multiple sclerosis

Fingolimod (Gilenya) is an immunosuppressive drug derived from the myriocin (ISP-1) metabolite of the fungus Isaria sinclairii. It is a structural analogue of sphingosine and gets phosphorylated by sphingosine kinase 2 in the cell.

Dr. Ron


Articles

Prevalence of use and the risk of adverse effects associated with complementary and alternative medicine in a cohort of patients receiving warfarin

(Leung, Shalansky et al. 2009) Download

BACKGROUND: The use of complementary and alternative medicine (CAM), including orally administered herbals, botanicals, vitamins, and supplements, may pose a risk to patients on warfarin therapy. OBJECTIVE: To estimate the prevalence of CAM use among patients taking warfarin and evaluate the impact of CAM exposure on the risk of warfarin-related adverse effects. METHODS: A survey was administered to hospital inpatients and clinic outpatients on drug exposure (including CAM) over the previous month, self-reported bleeding events, use of alcohol and vitamin K-rich foods, and medical conditions. Prescription medication use was verified, and laboratory records were checked for out-of-range international normalized ratios (INRs) (defined as INR >4 or <2). The use of CAM, including products with reported or theoretical interactions with warfarin, was compared between patients with and without self-reported bleeding or out-of-range INR. RESULTS: Among the 314 patients who completed the survey, 44.3% reported using CAM at least weekly. Potentially interacting CAM was used by 34.1% of all patients, or 18.2% if vitamin E was excluded as an interacting CAM. Vitamin E was used by 24.2% of all patients and 71.0% of those who used potentially interacting CAM. There was no significant difference in CAM use or consumption of vitamin K-rich foods between patients with and without INRs greater than 4 or for patients with and without INRs less than 2. CONCLUSIONS: The use of potentially interacting CAM in this cohort was higher than the use previously reported among patients on warfarin therapy. However, exposure to CAM was not associated with an increase in the risk of self-reported bleeding or out-of-range INR.

Risk of warfarin-related bleeding events and supratherapeutic international normalized ratios associated with complementary and alternative medicine: a longitudinal analysis

(Shalansky, Lynd et al. 2007) Download

STUDY OBJECTIVE: To determine the risk of bleeding and supratherapeutic international normalized ratios (INRs) associated with use of complementary and alternative medicine (CAM) in patients receiving warfarin. DESIGN: Prospective, longitudinal study. SETTING: An acute care, academic and research hospital in Canada. PATIENTS: A total of 171 adults who were prescribed warfarin anticoagulation therapy for an expected duration of at least 4 months after enrollment. INTERVENTION: Patients were asked to complete a 16-week diary by recording bleeding events and exposure to factors previously reported to increase the risk of bleeding and supratherapeutic INRs, including CAM consumption. MEASUREMENTS AND MAIN RESULTS: Prescription, medical, and laboratory records were reviewed. Risk factors for bleeding events and supratherapeutic INR (at least 0.5 units above the target range) were evaluated longitudinally by using generalized estimating equation (GEE) modeling. Of the 171 patients completing a diary, 87 (51%) reported at least one bleeding event and 36 (21%) had a supratherapeutic INR. Seventy-three patients (43%) indicated they had used at least one CAM product previously reported to interact with warfarin. Warfarin use of less than 3 months' duration was the only statistically significant risk factor identified for supratherapeutic INR. The CAM therapies associated with an increased risk of self-reported bleeding included cayenne, ginger, willow bark, St. John's wort, and coenzyme Q(10). Use of more than one CAM while receiving warfarin was also a significant risk factor. Two CAMs were independently associated with an increased risk of self-reported bleeding: coenzyme Q(10) (odds ratio [OR] 3.69, 95% confidence interval [CI] 1.88-7.24) and ginger (OR 3.20, 95% CI 2.42-4.24). Other risk factors significantly associated with increased bleeding included high target INR (2.5-3.5), diarrhea, acetaminophen use, increased alcohol consumption, and increased age. CONCLUSIONS: The use of CAM by patients receiving warfarin is common, and consumption of coenzyme Q(10) or ginger appears to increase the risk of bleeding in this population.

Dietary choline and betaine intakes in relation to concentrations of inflammatory markers in healthy adults: the ATTICA study

(Detopoulou, Panagiotakos et al. 2008) Download

BACKGROUND: Choline and betaine are found in a variety of plant and animal foods and were recently shown to be associated with decreased homocysteine concentrations. OBJECTIVE: The scope of this work was to investigate the associations between dietary choline and betaine consumption and various markers of low-grade systemic inflammation. DESIGN: Under the context of a cross-sectional survey that enrolled 1514 men (18-87 y of age) and 1528 women (18-89 y of age) with no history of cardiovascular disease (the ATTICA Study), fasting blood samples were collected and inflammatory markers were measured. Dietary habits were evaluated with a validated food-frequency questionnaire, and the intakes of choline and betaine were calculated from food-composition tables. RESULTS: Compared with the lowest tertile of choline intake (<250 mg/d), participants who consumed >310 mg/d had, on average, 22% lower concentrations of C-reactive protein (P < 0.05), 26% lower concentrations of interleukin-6 (P < 0.05), and 6% lower concentrations of tumor necrosis factor-alpha (P < 0.01). Similarly, participants who consumed >360 mg/d of betaine had, on average, 10% lower concentrations of homocysteine (P < 0.01), 19% lower concentrations of C-reactive protein (P < 0.1), and 12% lower concentrations of tumor necrosis factor-alpha (P < 0.05) than did those who consumed <260 mg/d. These findings were independent of various sociodemographic, lifestyle, and clinical characteristics of the participants. CONCLUSIONS: Our results support an association between choline and betaine intakes and the inflammation process in free-eating and apparently healthy adults. However, further studies are needed to confirm or refute our findings.

Is there a new component of the Mediterranean diet that reduces inflammation?

            (Zeisel 2008) Download

Folate and cancer: how DNA damage, repair and methylation impact on colon carcinogenesis

            (Duthie 2010) Download

Inappropriate diet may contribute to one third of cancer deaths. Folates, a group of water-soluble B vitamins present in high concentrations in green, leafy vegetables, maintain DNA stability through their ability to donate one-carbon units for cellular metabolism. Folate deficiency has been implicated in the development of several cancers, including cancer of the colorectum, breast, ovary, pancreas, brain, lung and cervix. Generally, data from the majority of human studies suggest that people who habitually consume the highest level of folate, or with the highest blood folate concentrations, have a significantly reduced risk of developing colon polyps or cancer. However, an entirely protective role for folate against carcinogenesis has been questioned, and recent data indicate that an excessive intake of synthetic folic acid (from high-dose supplements or fortified foods) may increase human cancers by accelerating growth of precancerous lesions. Nonetheless, on balance, evidence from the majority of human studies indicates that dietary folate is genoprotective against colon cancer. Suboptimal folate status in humans is widespread. Folate maintains genomic stability by regulating DNA biosynthesis, repair and methylation. Folate deficiency induces and accelerates carcinogenesis by perturbing each of these processes. This review presents recent evidence describing how these mechanisms act, and interact, to modify colon cancer risk.


References

Detopoulou, P., D. B. Panagiotakos, et al. (2008). "Dietary choline and betaine intakes in relation to concentrations of inflammatory markers in healthy adults: the ATTICA study." Am J Clin Nutr 87(2): 424-30.

Duthie, S. J. (2010). "Folate and cancer: how DNA damage, repair and methylation impact on colon carcinogenesis." J Inherit Metab Dis.

Leung, V. W., S. J. Shalansky, et al. (2009). "Prevalence of use and the risk of adverse effects associated with complementary and alternative medicine in a cohort of patients receiving warfarin." Ann Pharmacother 43(5): 875-81.

Shalansky, S., L. Lynd, et al. (2007). "Risk of warfarin-related bleeding events and supratherapeutic international normalized ratios associated with complementary and alternative medicine: a longitudinal analysis." Pharmacotherapy 27(9): 1237-47.

Zeisel, S. H. (2008). "Is there a new component of the Mediterranean diet that reduces inflammation?" Am J Clin Nutr 87(2): 277-8.