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Content 7


The Doctor and the Pharmacist

Radio Show Articles:
October 6, 2012

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A Link Between Vitamin D and Vitiligo
Vitamin D Does Not Prevent Upper Respiratory Tract Infections
Endometriosis Associated with Inflammatory Bowel Disease
Proton-Pump Inhibitors Increase Serious Infection Rates in Decompensated Cirrhosis
Ultraviolet Device Kills Superbugs
Drug Companies Discount Coupons
Botulinum Toxin and Anticholinergic Therapy Yield Similar Outcomes in Urinary Incontinence
Hormone Therapy Soon After Menopause: New Findings Get Attention
Bringing Depression in Reproductive-Aged Women out of the Shadows
Can Aspirin Reduce the Risk of Depression?
Long-Term Health Benefits of Gastric Bypass Surgery
The Next Big Thing for Metastatic Breast Cancer
Does Fructose Fuel Cancer?

MM: This is a very exciting possible link between certain forms of vitiligo and vitamin D deficiency. Vitiligo is the tendency to have white or de-pigmented splotches or areas on the body. It can be an embarassing condition that torments the person who has it.
J Dermatol 2012 Oct; 167:815
A Link Between Vitamin D and Vitiligo
These findings may explain why treatments are effective in some, but not all, vitiligo patients.
Vitiligo is an acquired depigmenting disorder of uncertain etiology. Anecdotal reports imply that the disease responds to topical vitamin D analogs, suggesting that vitamin D may be involved in its pathogenesis. To investigate the relationship between vitamin D and vitiligo, investigators in China looked at polymorphisms in vitamin D receptor genes in 749 vitiligo patients and 763 control subjects.
Polymorphisms in the BsmI, ApaI, and TaqI alleles were significantly less frequent in vitiligo patients than in controls. A fourth allele, FokI, was not associated with predisposition to vitiligo. In addition, serum 25(OH) vitamin D levels were measured in 171 vitiligo patients and 150 controls. There was a dose–response relationship between higher 25(OH) vitamin D levels and protection from vitiligo.
Comment: One of dermatologists' great needs is a reliable treatment for vitiligo. Study results on the role of vitamin D analogs in vitiligo have conflicted. These results indicate that the variability may result from genetic polymorphisms in the vitamin D receptor, which would allow some patients, but not others, to respond to vitamin D analogs. Future studies evaluating the efficacy of vitamin D analogs are warranted, but with consideration of these polymorphisms in the efficacy analysis. The findings may also explain why phototherapy, which is known to increase vitamin D levels in the skin, is effective in some, but not all, vitiligo patients. The results also suggest that it may be possible to reduce the incidence or progression of vitiligo by ensuring that at-risk patients do not become vitamin D deficient.
— Craig A. Elmets, MD Published in Journal Watch Dermatology October 5, 2012
Citation(a): Li K et al. The association of vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D levels with generalized vitiligo. Br J Dermatol 2012 Oct; 167:815.
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MM: This study confounds me. I have placed hundreds of patients on vitamin D3 DAILY supplementation and have received consistent feedback that their coughs and colds, allergy related events and other maladies have either disappeared completely, ameliorated substantially or have not shown up at all since starting the supplements compared to other years when they didn’t supplement. I would not rely on this one study of failure to disregard the hundreds/thousands of successful studies and articles that have appeared in the past few years.
JAMA 2012 Oct 3; 308:1333
Vitamin D Does Not Prevent Upper Respiratory Tract Infections
No benefit of supplementation was noted, either in incidence or severity of URTIs.
Low vitamin D levels are associated with excess risk for upper respiratory tract infections (URTIs), but clinical trials of supplementation have been small and inconclusive. In a New Zealand–based study, researchers randomized 322 healthy adults (mean baseline 25-hydroxyvitamin D level, 29 ng/mL) to monthly oral vitamin D3 supplementation (200,000 IU for 2 months, followed by 100,000 IU for 16 months) or placebo. Participants reported no substantial previous vitamin D use.
Ninety-one percent of participants were followed for 18 months. Mean 25-hydroxyvitamin D levels increased to 50 ng/mL in the intervention group and remained unchanged in the placebo group. The incidence of URTIs during the study was similar in each group (mean, 3.7 episodes per person), as was URTI severity.
Comment: An editorialist notes the long list of agents and approaches that have failed to prevent URTIs, includingEchinacea, zinc, steam inhalation, vitamin C, and garlic. Vitamin D has just joined that list — at least for people whose baseline vitamin D status seems to be adequate.
— Thomas L. Schwenk, MD Published in Journal Watch General Medicine October 4, 2012
Citation(s): Murdoch DR et al. Effect of vitamin D3 supplementation on upper respiratory tract infections in healthy adults: The VIDARIS randomized controlled trial.
JAMA 2012 Oct 3; 308:1333.
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MM: Endometriosis will frequently respond to transdermal (topical) Bio-identical Progesterone (P4). Combining P4 with Vitamin D-3 at an early stage of diagnosis may stabilize the body, enhance the immune system, improve the patient’s Quality of Life (QOL) and decrease the likelihood of developing these other immuno-deficiency conditions. The use of Low Dose Naltrexone (LDN) may be a prescription alternative that has been shown to be both safe and effective for other immuno-deficiency conditions such as rheumatoid arthritis, Crohn’s disease, Fibromyalgia (FMS) andMultiple Sclerosis (MS), among others.
Gut 2012 Sep; 61:1279
Endometriosis Associated with Inflammatory Bowel Disease
Women with endometriosis had elevated risk for ulcerative colitis and Crohn disease, even more than 20 years after their diagnoses.
Endometriosis is the result of implantation of menstrual products from the endometrium that are not cleared by the immune system. To determine whether endometriosis is associated with inflammatory bowel disease (IBD) — also an autoimmune-related disorder — investigators in Denmark conducted a nationwide cohort study involving 37,661 women (mean age, 38.6 years) hospitalized with endometriosis during a 40-year period.
During >492,000 person-years of follow-up, the standardized incidence ratio was 1.5 for ulcerative colitis and 1.6 for Crohn disease. The risk for ulcerative colitis was highest among women diagnosed with endometriosis between the ages of 25 and 34. The risk for Crohn disease was highest among women diagnosed before age 25. The mean interval between endometriosis diagnosis and diagnosis of IBD was 10.8 years for ulcerative colitis and 9.8 years for Crohn disease. Risks for IBD remained elevated after >20 years of observation and were even higher when the analysis was confined to women with surgically verified endometriosis.
Comment: These data suggest a shared immunologic basis for endometriosis and IBD. Patients with endometriosis and clinical features associated with IBD should undergo gastrointestinal evaluation.
— Douglas K. Rex, MD Published in Journal Watch Gastroenterology October 5, 2012
Citation(s): Jess T et al. Increased risk of inflammatory bowel disease in women with endometriosis: A nationwide Danish cohort study. Gut 2012 Sep; 61:1279.
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Aliment Pharmacol Ther 2012 Sep 11
Proton-Pump Inhibitors Increase Serious Infection Rates in Decompensated Cirrhosis
However, H2 receptor antagonists did not increase risk for infections and offer a reasonable alternative.
Acid-suppressive therapy predisposes users to bacterial overgrowth and bacterial translocation. A previous study suggests that proton-pump inhibitor (PPI) use is associated with serious infections in cirrhotic patients (JW Gastroenterol Apr 20 2012) but was limited in size and did not investigate other acid-suppressive agents.
In a retrospective, propensity-matched cohort study, investigators examined U.S. Veterans Health Administration data to compare rates of serious infection associated with use of PPIs, H2 receptor antagonists (H2RAs), or no gastric acid suppressant in patients who began use after development of decompensated cirrhosis. Serious infections were defined as any infection requiring hospitalization, and a subset of these infections was classified as related to acid suppression (pneumonia, bacteremia, Clostridium difficile, and spontaneous bacterial peritonitis).
A total of 4181 patients were included in the analysis (1905 PPI users, 248 H2RA users, and 2028 nonusers of gastric acid suppressants). Compared with nonusers, PPI users had a higher incidence of serious infections (adjusted hazard ratio, 1.66; 95% confidence interval, 1.31–2.12) as well as acid-suppression–related infections (AHR, 1.75; 95% CI, 1.32–2.34). However, no significant difference was observed in rates of either all serious infections or acid-suppression–related infections between H2RA users and nonusers.
Comment: Although this study was retrospective, its sample size was large, its design minimized prevalent bias and confounding, and it included a comparison of PPIs and H2RAs. These results confirm previous findings that PPI use increases risk for serious infections in patients with decompensated cirrhosis but show no such increased risk with H2RAs. One possible explanation is that the two drug classes have different degrees of acid-suppressing potency. From a clinical standpoint, these results suggest that switching from a PPI to an H2RA in patients with decompensated cirrhosis who need acid suppression would be a reasonable approach.
— Atif Zaman, MD, MPH Published in Journal Watch Gastroenterology October 5, 2012
Citation(s): Bajaj JS et al. Proton pump inhibitors are associated with a high rate of serious infections in veterans with decompensated cirrhosis. Aliment Pharmacol Ther 2012 Sep 11; [e-pub ahead of print].
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Ultraviolet Device Kills Superbugs
Microorganisms lurking on bed rails, tables, doorknobs, and other surfaces in hospitals are causing a more than $30-billion problem for the U.S. healthcare system. Now, a new device has been introduced that is a portable disinfection system using pulses/bursts of the inert gas xenon at a rapid speed and high intensity in an ultraviolet flash lamp, producing UVC radiation. At certain wavelengths, this UV light penetrates the outer coatings of bacteria, viruses, mold, and spores. Xenex's CEO says "The light acts like a needle—it pierces the cell walls and prevents them from replicating."
This method is used in addition to traditional surface cleaning. The device is turned on with a remote control after the room is free of occupants. The entire process takes about 10 minutes and leaves no residue or gas in the room.
Xenon UV light is advantageous to hospitals because it's less expensive, quicker, and less harmful than traditional ways of automated sterilization, like using hydrogen peroxide gas or mercury lamps. It is used in sterilizing water and is approved by the FDA for the disinfection of food. 
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Drug Companies Discount Coupons
A magazine ad for AndroGel shows a discount card that allows consumers to pay "as little as $10 per month." GSK announces in another magazine that it offers discount coupons for the popular inhaler Advair, and a TV commercial for Nexium notes that if consumers can't afford the heartburn drug, its manufacturer, AstraZeneca, "may be able to help."
Drug companies say the coupons help Americans get the medicine they need, however, the insurance industry is concerned that they drive patients toward more expensive brand-name drugs, leaving insurers to cover the full cost, which then gets passed on to consumers in the form of higher premiums. 
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Botulinum Toxin and Anticholinergic Therapy Yield Similar Outcomes
in Urinary Incontinence

Oral anticholinergic therapy and injectable onabotulinumtoxinA are similarly efficacious in treating urgency urinary incontinence, according to a New England Journal of Medicine study.
Some 250 women without neurological disease who had moderate-to-severe urgency incontinence were randomized either to a single injection of onabotulinumtoxinA into the detrusor muscle plus a daily oral placebo for 6 months, or to a single injection of saline plus dose-escalation with a daily oral anticholinergic for 6 months.
The primary outcome — the mean number of urgency incontinence episodes — was similarly reduced in the two groups (roughly 3 fewer episodes/day). OnabotulinumtoxinA recipients were twice as likely as anticholinergic recipients to report complete resolution of urgency incontinence (27% vs. 13%). Dry mouth was significantly more common with anticholinergic therapy, whereas urinary tract infections and incomplete bladder emptying requiring catheterization were significantly more common with onabotulinumtoxinA.
The researchers conclude that "the choice between these therapies should take into account the differing regimens and routes of administration and the side-effect profiles."
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Hormone Therapy Soon After Menopause: New Findings Get Attention
Patients may want to discuss widely reported findings about hormone therapy for early menopausal symptoms presented Wednesday evening at a North American Menopause Society meeting.
The Kronos Early Estrogen Prevention Study (KEEPS) randomized some 700 women within 3 years after menopause to 4 years' treatment with micronized progesterone (Prometrium) plus either oral conjugated equine estrogens (Premarin, 0.45 mg/day), transdermal estradiol (Climara patch, 50 μg/day), or placebo.
"The data showed improvements in cognition, mood, menopausal symptoms, and sexual function in younger women," Kronos Longevity Research Institute director S. Mitchell Harman said in a news release. "In addition, some measures showed slight evidence that hormone therapy might be cardio-protective in this age group, although results were not definitive and would require additional study."
The trials results have not yet been published.
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J Womens Health (Larchmt) 2012 Aug; 21:830
Bringing Depression in Reproductive-Aged Women out of the Shadows
Among the 10% of pregnant and nonpregnant women who reported symptoms of a past-year major depressive episode, the disorder was undiagnosed in almost 60%.
Depression, a leading cause of disability in the U.S., often goes undiagnosed. Do prevalence, diagnosis, and treatment of depression differ in pregnant and nonpregnant women? Researchers analyzed data from the National Surveys on Drug Use and Health. Of more than 77,000 women of reproductive age (range, 18–44) who participated, 9000 reported pregnancy status and whether they had experienced a major depressive episode (MDE) during the year preceding the survey (past-year MDE). Respondents also indicated whether they received diagnoses and treatment including prescription medications, counseling, or hospitalization.
Overall, 10.9% of respondents experienced past-year MDE (1.2 million women per year in 2005–2009). Prevalence was 7.7% in pregnant women and 11.1% in nonpregnant women (P<0.001). Among women with past-year MDE, 58.8% did not receive clinical diagnoses. Rates of undiagnosed depression were higher in pregnant woman than in nonpregnant women (65.9% and 58.6%, respectively), but the difference was not statistically significant. Black and Latina women were most likely to have undiagnosed depression (73.1% and 68.0%, respectively). In all, 49.6% of pregnant women and 53.7% of nonpregnant women received mental health treatment within the past year; however, 38.9% of all women reported unmet treatment needs. Treatment barriers included cost (54.8%), opposition to treatment (41.7%), perceived stigma (26.3%), and time or transportation limitations (18.1%).
Comment: The authors concluded that pregnant and nonpregnant women with depression had similar likelihood of diagnosis and treatment. An editorialist notes that if 10% of U.S. women developed a fatal form of cancer that went undiagnosed 60% of the time, public outrage would result; by contrast, most individuals with mental health disorders continue to be disenfranchised by the medical system. Women's health care clinicians who are vigilant in identifying signs of depression in their patients can pave the way for referral, diagnosis, and appropriate treatment.
— Anne A. Moore, APN, WHNP/ANP-BC, FAANP Published in Journal Watch Women's Health September 6, 2012
Citation(s): Ko JY et al. Depression and treatment among U.S. pregnant and nonpregnant women of reproductive age, 2005–2009. J Womens Health (Larchmt) 2012 Aug; 21:830.
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MM: If lowering homocysteine levels is truly effective for treating depression, then there is possibly another viable use for our Synergy B, Vitamin B Complex. We have found this product useful for thinning hair, Adrenal Fatigue and general stress. Depression would be a logical use but this study does not dewmonstrate that added benefit. Perhaps we will se another study that supportd thid function in the near future.
Transl Psychiatry 2012 Aug 14; 2:e151
Can Aspirin Reduce the Risk of Depression?
In older men, the combination of high plasma homocysteine levels and aspirin use is associated with a lower risk for depression.
High total plasma homocysteine levels (tHcy), associated with platelet activation and endothelial dysfunction, have been linked to increased risks for cardiovascular disease, stroke, and depression. Epidemiologists have speculated that if tHcy did directly contribute to depression, reducing levels might prevent as many as 15% of cases of late-life depression. Using records from 3687 cognitively unimpaired men (age range, 69–87) participating in the Australian Health In Men Study, investigators examined cross-sectional associations among depression, tHcy levels, and self-reported use of aspirin (the most common antiplatelet agent) and B vitamins (which reduce tHcy levels).
Overall, 513 men had current or past depression (14%; 165 men had current depression), and 934 (25%) had high tHcy levels. Results were adjusted for demographics, smoking, antidepressant use, and scores on an index of 17 common medical conditions predicting 1-year mortality. Risk for depression was increased with high tHcy (odds ratio, 1.60) but was lower in men with high tHcy who took aspirin (OR, 0.57). Consumption of B vitamins was not associated with reduced risk.
Comment: These investigators previously hypothesized that aspirin might increase depression risk in elderly men due to bleeding or other medical complications and that aspirin use per se is elevated among older depressed males presumably because these patients have more medical comorbidities. However, these findings suggest that aspirin might actually help patients with high tHcy to avoid depression. Studies are indicated to ascertain the benefit of routine tHcy assessment in depressed elderly patients. Other studies looking more broadly at relationships between nonsteroidal antiinflammatory drugs and depression have yielded contradictory findings (JW Psychiatry May 2 2011 and May 21 2012). In the absence of medical contraindications, aspirin for older patients with high tHcy and those prone to depression might prove to be a low-risk, high-yield intervention.
— Joel Yager, MD Published in Journal Watch Psychiatry September 24, 2012
Citation(s): Almeida OP et al. Aspirin decreases the risk of depression in older men with high plasma homocysteine. Transl Psychiatry2012 Aug 14; 2:e151.
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JAMA 2012 Sep 19; 308:1122
Long-Term Health Benefits of Gastric Bypass Surgery
Diabetes remission rate was 62% at 6 years, almost 10-fold higher than in severely obese patients who did not have bariatric surgery.
JW Gen Med Sep 6 2012). In this Utah-based prospective cohort study, researchers evaluated weight, diabetes, and other cardiovascular risk factors at baseline, 2 years, and 6 years in 418 severely obese patients (mean body-mass index, 47 kg/m2; mean age, 42; 84% women) who underwent Roux-en-Y gastric bypass surgery, a control group of 417 patients with similar clinical and demographic features who sought but did not undergo surgery, and a similarly obese population-based control group of 321 patients.
Mean weight loss in the surgical group was 35% at 2 years and 28% at 6 years; weight remained essentially unchanged in both control groups. Diabetes remission rates at 6 years were 62% in the surgery group versus 6% to 8% in the control groups; hypertension remission rates were 42% versus 9% to 18%. A total of 29 deaths had occurred within 6 years (12 in the surgical group and 17 in the combined control groups). Incidence of suicide was significantly higher in the surgery group than the control groups (4 vs. 0).
Comment: These bariatric surgery patients experienced significant improvement in several cardiovascular risk factors, but we still do not have a complete picture of long-term mortality or healthcare resource use. The apparent higher risk for suicide in the surgical group could be related to the substantial emotional and behavioral changes that can occur after surgery in severely obese patients.
— Thomas L. Schwenk, MD Published in Journal Watch General Medicine September 25, 2012
Citation(s): Adams TD et al. Health benefits of gastric bypass surgery after 6 years. JAMA 2012 Sep 19; 308:1122.
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J Clin Oncol 2012 Sep 10; 30:3234
The Next Big Thing for Metastatic Breast Cancer
The drug-antibody conjugate trastuzumab emtansine demonstrated single-agent activity in patients with previously treated HER2-positive disease.
Even with the recent approval of pertuzumab as a component (along with trastuzumab and docetaxel) of a first-line regimen for patients with human epidermal growth factor receptor 2 (HER2)–positive, metastatic breast cancer, the anticipated approval of trastuzumab emtansine (T-DM1) is eagerly awaited by oncologists as a treatment for patients with progressive HER2-positive breast cancer followin g treatment with trastuzumab. Indeed, clinical experience with T-DM1 — a fusion molecule combining trastuzumab with a cytotoxic (maytansine) utilizing a stable linker (see illustration) — has shown robust clinical activity following prior anti-HER2 therapy with relatively modest toxicity (J Clin Oncol 2011 Feb; 29:398).
Now, investigators have conducted an industry-supported, single-arm, phase II clinical trial to evaluate the effectiveness of T-DM1 (3.6 mg/kg intravenously, every 3 weeks) in 110 patients with metastatic HER-2-positive breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. Patients had previously received a median of seven prior nonendocrine agents.
At median follow-up of 17.4 months, the objective response rate (the primary objective) was 34.5%, the clinical benefit rate (inclusive of stable disease) was 48.2%, and median progression-free survival (PFS) was 6.9 months. T-DM1 was well tolerated. Most adverse events were grade 1 or 2. The most common events of any grade were fatigue, nausea, and thrombocytopenia. Grade 3 or 4 thrombocytopenia occurred in 9.1% of patients, and grade 3 fatigue occurred in 4.5%.
Comment: T-DM1 was recently shown to be superior to combination capecitabine and lapatinib in metastatic breast cancer patients who were not as heavily pretreated as those in the current study (JW Oncol Hematol Jul 3 2012). T-DM1 will be rapidly embraced by clinical oncologists once it is approved, and the future development of this agent will likely move to earlier-stage breast cancer and be used in combination with other HER2-targeted agents such as pertuzumab.
— William J. Gradishar, MD Published in Journal Watch Oncology and Hematology October 2, 2012
Citation(s): Krop IE et al. A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2–positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. J Clin Oncol 2012 Sep 10; 30:3234.
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Does Fructose Fuel Cancer?
Excessive intake from processed foods and drinks raises concerns; fructose from whole foods appears safe
By Craig Weatherby
According to the U.S. Department of Agriculture, the average American downs more than 65 pounds of high fructose corn syrup (HFCS) per year. And the most recent official U.S. diet-health survey found that more than 10 percent of the average American’s daily calories come from fructose … with sweetened drinks being the single biggest source. Some critiques of HFCS – versus the fructose found in plant foods and cane sugar – appear scientifically sound.

For example, see “Corn-Sweetened Sodas High in Pro-Aging Agent”.

But most attacks on HFCS cite evils that apply equally to cane sugar … which contains even more fructose: see “Fructose Called Most Dangerous Sugar”, “Fructose May Promote Obesity & Inflammation”, “Corn Syrup vs. Sugar in Weight Control”, and “High-Fructose Corn Syrup Declared Unnatural”. Earlier this month, scientists from the University of Maryland, Baltimore and Boston University Medical Center published a review of the evidence, which affirmed prior evidence that fructose promotes cancer.

As they wrote, “Fructose intake is associated with increased risk of pancreatic and small intestinal cancers, and possibly others … [it] is associated with more aggressive cancer behavior and may promote metastasis.” (Port AM et al. 2012) And as they noted, this fact has worrying public health implications: “Fructose has become ubiquitous in our food supply, with the highest consumers being teens and young adults … understanding the potential health consequences of fructose and its role in chronic disease development is of critical importance.”

Fructose may fuel cancer
It’s well known that excessive intake of sugar – and refined starches like white flour, which the body converts into glucose almost instantly – promotes cancer growth. But “sugar” is an inexact term that covers diverse chemical compounds. Sugars include single molecules like glucose and fructose, and combinations like sucrose and high-fructose corn syrup (HFCS). Cane sugar consists entirely of sucrose, which is also the dominant sugar in fruits and vegetables. Sucrose is a 50/50 combination of glucose and fructose, which the body splits apart almost instantly.

HFCS actually contains a bit less fructose than sucrose does, featuring ratios of fructose to glucose that range narrowly from 42/55 (soft drinks) or 42/53 (processed foods, cereals, and baked goods). Some claim that HFCS is worse because its glucose and fructose are not chemically bound to each other, while they are bound together in cane sugar. But the body immediately cleaves apart the glucose and fructose in cane sugar, making this a distinction without a metabolic difference.

Dig deeper, however, and we find that excessive intake of fructose – regardless of the source – promotes cancer.

What makes fructose cancer-friendly?
Why would fructose be worse than glucose in this regard?

As the Baltimore-Boston team wrote, “Whereas glucose favors overall growth kinetics, fructose enhances protein synthesis and appears to promote a more aggressive cancer phenotype.” (Port AM et al. 2012) The body prefers fructose over glucose as a raw material from which to make nucleic acids … compounds essential to growth of tissues … especially tumors. Fructose also promotes cancer growth in other ways, including altered cellular metabolism, increased generation of free radicals, DNA damage, and inflammation. Worse, epidemiological studies have linked high intake of fructose (and other sugars) to pancreatic cancer, and to type 2 diabetes and obesity … which are risk factors for pancreatic cancer.

However, the problem is not fructose per se, but excessive intake of this single-molecule sugar. Despite the fact that the fructose in plant foods is identical to the fructose in HFCS, people who report high intakes of fruits and vegetables show a reduced risk of pancreatic cancer. How can we explain this difference? Compared with fruits and vegetables, processed foods and drinks sweetened with HFCS contain large amounts of fructose. And fruits and vegetables abound in compounds (fiber, flavonoids, and carotenoids) linked to reduced risk of pancreatic cancer and other cancers.

Sources: Aune D, Chan DS, Lau R, Vieira R, Greenwood DC, Kampman E, Norat T. Carbohydrates, glycemic index, glycemic load, and colorectal cancer risk: a systematic review and meta-analysis of cohort studies. Cancer Causes Control. 2012 Apr;23(4):521-35. Epub 2012 Mar. Aune D, Chan DS, Vieira AR, Navarro Rosenblatt DA, Vieira R, Greenwood DC, Cade JE, Burley VJ, Norat T. Dietary fructose, carbohydrates, glycemic indices and pancreatic cancer risk: a systematic review and meta-analysis of cohort studies. Ann Oncol. 2012 Oct;23(10):2536-46. Epub 2012 Apr 26. Aune D, Greenwood DC, Chan DS, et al. Body mass index, abdominal fatness and pancreatic cancer risk: a systematic review and non-linear dose-response meta- analysis of prospective studies. Ann Oncol. 2012;23:843-852. Benson A, Myerson R, Sasson A. Pancreatic, Neuroendocrine GI, and Adrenal Cancers Cancer Management: 14th Edition ebook. Huxley R, Ansary-Moghaddam A, Berrington de Gonzalez A, Barzi F, Woodward M. Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer. 2005;92:2076-2083. Iodice S, Gandini S, Maisonneuve P, et al. Animal fat consumption and pancreatic cancer incidence: evidence of interaction with cigarette smoking. Ann Epidemiol. 2005;15:500-508. Jansen RJ, Robinson DP, Stolzenberg-Solomon RZ, et al. Fruit and vegetable consumption is inversely associated with having pancreatic cancer. Cancer Causes Control. 2011;22(12):1613-1625. Larsson SC, Bergkvist L, Wolk A. Consumption of sugar and sugar sweetened foods and the risk of pancreatic cancer in a prospective study. Am J Clin Nutr. 2006;84(5):1171-1176. Liu H, Huang D, McArthur DL, et al. Fructose induces transketolase flux to promote pancreatic cancer growth. Cancer Res. 2010;70:6368-6376. Meyer KA, Kushi LH, Jacobs DR, et al. Carbohydrates, dietary fiber, and incident type 2 diabetes in older women. Am J Clin Nutr. 2000;71:921-930. Michaud DS, Liu S, Giovannucci E, Willett WC, Colditz GA, Fuchs CS. Dietary sugar, glycemic load, and pancreatic cancer risk in a prospective study. J Natl Cancer Inst. 2002 Sep 4;94(17):1293-300. Montonen J, Jarvinen R, Heliovaara M, et al. Food consumption and the incidence of type II diabetes mellitus. Eur J Clin Nutr. 2005;59:441-448. Mueller NT, Odegaared A, Anderson K, et al. Soft drink and juice consumption and risk of pancreatic cancer: the Singapore Chinese health study. Cancer Epidemiol Biomarkers Prev. 2010;19(2):447-455. National Cancer Institute. Accessed at http://www.cancer.gov/cancertopics/types/pancreatic. Perez-Pozo SE, Schold J, Nakagawa T, et al. Excessive fructose intake induces the features of metabolic syndrome in healthy adult men: role of uric acid in the hypertensive response. Int J Obes (Lond). 2010;34:454-461. Port AM, Ruth MR, Istfan NW. Fructose consumption and cancer: is there a connection? Curr Opin Endocrinol Diabetes Obes. 2012 Oct;19(5):367-74. Stanhope KL, Schwarz JM, Keim NL, et al. Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J Clin Invest. 2009;119:1322-1334. United States Department of Agriculture. Accessed at http://www.usda.gov/factbook/chapter2.pdf. Vos MB, Kimmons JE, Gillespie C, et al. Dietary fructose consumption among US children and adults: the third national health and nutrition examination survey. Medscape J Med. 2008;10(7):160.

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