Category Archives: Nutrition

Improvement in obesity rate?

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In case you didn’t see it, this article link, OBESITY IN YOUNG IS SEEN AS FALLING IN – THE NEW YORK TIMES, appeared in multiple news outlets (December 10, 2012) and suggests that in some cities there has been a modest reduction in obesity rates of 3-5%.

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Does bone density improve with IBD therapy?

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Long term followup is needed to determine the significance of low bone mineral density (BMD) in children and adolescence with IBD; data with 2 year followup is available (JPGN 2012; 55: 511-18).

In this study from Sweden, 144 patients with IBD were enrolled and 126 were available at 2-year followup (2003-2005).  Among the 144 patients, there were 93 males and 83 with UC. Low BMD was noted in children with both UC and CD for the lumbar spine at baseline and no improvement was noted at 2 years.  Only boys had lower BMD z scores for the lumbar spine (LS) (-1.1); girls had normal LS z scores (0).

While the investigators could not demonstrate catch up in bone mineral density, they note that gains in BMD may accrue beyond late adolescence into early adulthood; this takes place after completion of linear growth.  In the subgroup of subjects in early adulthood, there was improvement in BMD:

  • For boys: from -1.7 at baseline (age 17.9) to -0.5 at followup (age 20.0)
  • For girls: from -0.4 at baseline (age 17.1) to 0.4 at followup (age 19.2)

With greater use of biologic therapy, these data are likely to change.  Among medical treatments, only biologic therapies have been shown to improve bone formation and improve catchup growth.

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Additional references:

  • -JPGN 2011;53: 361. Similar prevalence of low Vitamin D as general population –58% with less than 32.
  • -JPGN 2011; 53: 11. Guidelines for low bone mineral density in IBD.
  • -JPGN 2009; 48: 538. Need to adjust bone density for bone age.
  • -Gastroenterol 2009; 136: 123. Longitudinal bone health study. Steroids did NOT adversely affect bones. n=78.
  • -Clin Gastro & Hep 2008; 6: 1378. IFX improves biomarkers of bone formation.
  • -J Pediatr 2008; 153: 454, 484. Use of biomarkers of bone turnover in Crohn dz; even when controlling for other factors like delayed bone age, delayed puberty, etc, still evidence of decrease bone formation and increased resorption.
  • -JPGN 2007; 45: 538. Ca/Vit D supplements -no change in BMD in IBD patients over 12 months.
  • -Clin Gastro & Hep 2007; 5: 721. DXA may not predict risk well.
  • -IBD 2007; 4: 416. Inflammation, not steroids, is key factor in bone mineral density.
  • -IBD 2006; 13: 42. Natural hx of bone mineral density in IBD; steroid dose did not correlate with BMD. Children did not have “catch up” bone density.
  • -JPGN 2006; 43: 597. Crohn’s patients had similar rate of fractures as siblings w/o IBD.
  • -Clin Gastro & Hep 2006; 4: 152. Osteoporosis in IBD.
  • -IBD 2006; 12: 797. Review of bone mineral density with IBD
  • -Clin Gastro & Hepatol 2005; 3: 113-121, 122-132 & editorial 110. In 1st article, budesonide better for bones than other steroids. In 2nd article, unable to show benefit of addition of etidronate to Ca++/Vit D.
  • -NEJM 2002; 351: 868. Intermittent steroids in nephrotic syndrome did NOT change bone mineral density.
  • -Gastro 2001; 121: 1485-88. Tanning bed Rx of vitamin D deficiency.
  • -Gastro 2000; 119: 639-46. Alendronate increases BMD in pts c Crohn’s
  • -NEJM 1998; 339: 292-9/ J Bone Miner Res 2000; 15: 1006-13. Bisphosphonates effective in steroid-induced bone disease

Congenital Sucrase Isomaltase Deficiency

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Congenital Sucrase Isomaltase Deficiency (CSID) has an extensive review in a recent JPGN supplement (JPGN 2012; supplement 2: S1-47).

A concise update of the clinical aspects is provided by William Treem (S7-S13).   Specific points that he makes includes the following:

  • CSID was first described in 1960 by Weijers and colleagues
  • Sucrase-isomaltase gene (3q25-26) identified in 1992; now more than 55 mutations have been described.  At least one of the four most common mutations are identified in about 80% of affected individuals.
  • Prevalence: estimates range from 1 in 500 to 1 in 2000 in caucasians; the prevalence is lower in other populations.  Some patients suspected of having CSID may be heterozygotes with low enzyme activity (but not truly deficient).
  • Clinical features determined by degree of enzyme deficiency and amount of sugar and starch consumed.  In the U.S. typically 60% of calories consumed are derived from carbohydrates and 30% from sucrose.  A typical U.S. adult consumes 150 lb of sugar per year.
  • Classical presentation: severe watery diarrhea and poor weight gain in a 9- to 18-month old after exposure to juices, baby foods/fruits, and other starches.
  • Other symptoms: gas/bloating, abdominal pain, irritable bowel syndrome
  • Diagnosis: intestinal biopsy analysis.  A potential pitfall includes mishandling of biopsy specimens. An alternative means of diagnosis is the 13-C sucrose breath test.
  • Treatment: 1. dietary avoidance results in improvement in many, though only 10% respond fully to diet. 2. enzymatic treatment. Baker’s yeast (Saccharomyces cerevisiae) contains a sucrase.  Development of sacrosidase (Sucraid) from Baker’s yeast has allowed 81% of patients to consume an unrestricted diet.  Dosing: 1 mL with meals/snacks if <15 kg and 2 mL if >15 kg.
  • Despite sacrosidase treatment, 27% of patients required strict sucrose restriction with either mild or strict starch restriction to maintain acceptable suppression of symptoms.
  • What is not noted in this summary–cost information: sucraid may cost as much as $3700 per month.  A similar product in Europe costs about $400 per month

Multiple other articles in this supplement address related subjects.

On page S31, information is given from parent support group.  This parent support group (CSIDinfo.com) offers dietary advice specific for each phenotype (A,B,C,D and F) which is based on their disaccharidase levels, ability to outgrow symptoms, and tolerance of starch and maltodextrins.

On page S34, the major genetic mutations are discussed.  Use of genetic testing will detect the majority with CSID which could become an alternative means of diagnosing CSID in this population.

Additional Information

Less stress after gastrostomy tube placement

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It has been said that it is easier to feed a child with a gastrostomy tube (GT) than by mouth.  Now a study reports improved maternal stress after GT placement (JPGN 2012; 55: 562-66), perhaps because it is easier to provide nutrition.

34 mothers from Norway took part in questionnaires (before, 6 months after, and 18 months after) as part of a study (2003-2005) to see how gastrostomy placement in a child affects maternal stress levels.  Median maternal age was 32 years.  The study was limited by a suboptimal response rate of 59% (34 of 59) and only 19 mothers answered questionnaires at all 3 timepoints.

While all of the children had some peristomal complications, 85% of the mothers reported that their preoperative expectations were met and that their child had improved quality of life.  Mothers had reduced psychological  distress at 6 and 18 months following placement, including less anxiety.

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Six year outcomes with bariatric surgery

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Recently I read that suicides were increased in a group of individuals who underwent bariatric surgery.  This piqued my interest in finding the reference (JAMA 2012; 308: 1122-31 -21 authors).

This Utah study was a prospective trial between 2000-2011 involving 1156 severely obese participants between 18-72 years of age.  There were 3 groups.  The treatment group of 418 underwent Roux-en-Y gastric bypass (RYGB).  The second group (control group 1 =CG1) sought bariatric surgery but did not have surgery, and the third group (control group 2 =CG2) were a randomly selected population-based sample.

All participants had BMI ≥35.  RYGB group had average BMI of 47.3, CG1 was 46.3 and CG2 43.8.  The respective average age was 42.5, 43, and 49.4 years.  In CG1, 84 had undergone bariatric surgery by six years; in CG2 17 had undergone bariatric surgery by six years.

Results at six years:

  • Weight loss: RYGB (92.6% retained at followup): 27.7% loss of initial body weight; CG1 (92.6% followup) 0.2% weight gain, and 0% in CG2 (98% followup)
  • Diabetes remission rate: RYGB 62%, CG1 8%  and CG2 6%.  In addition, there was a 5- to 9-fold reduction in the risk of new diabetes in surgical patients compared to nonsurgical controls.
  • Mortality: No improvement in mortality was evident at six years.  RYGB 12 deaths, CG1 14 deaths  and CG2 3 deaths. None of the RYGB deaths occurred within 30 days of surgery.
  • Suicide:  all 4 patients who took their own life were in the RYGB group and 2 of 3 poisonings (undetermined intention) were in the RYGB group as well.
  • Mental health: The authors note an absence of improvement in the SF-36 mental component score in the surgical group which is in contrast to the SF-36 physical component score.
  • Glucose/insulin, Lipids & Blood pressure: Marked improvements in all of these parameters were noted at six years (Table 2).

It appears that much longer followup will be needed to show mortality benefits from bariatric surgery* and that preoperative/postoperative psychological assessment is needed.

* Mortality benefit has been evident in some studies (see references below)

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References:

  • -JAMA 2011 [doi: 10.1001/jama.2011.817]). Large study failed to show that roux-en-Y gastric bypass prolonged life. n=850 VA pts to 41,244 controls. Same group showed no cost savings during initial 3 yrs: Med Care 2010; 48: 989-98.
  • -NEJM 2011; 365: 1365. Increased frequency of bariatric surgery in adolescents.

Complications from surgery:
Early: bowel obstruction, DVT, GI bleed, leaks, pul embolism, wound infection
After 30 days: anastomotic stricture, bowel obstruction, gallstones, dehiscence, fistula, Bleeding, Incisional hernia, nutrient deficiencies (iron, B12; calcium, Vit D (w RYGB), folate, B6/riboflavin)
Suggested Nutrient Monitoring–every 3 months x 3, then yearly: Vitamin A, B12, Folate, Ceruloplasmin, Vit D-25OH, Iron studies, Zinc, thiamine, Selenium, Intact PTH, Mg, PT/PTT
Suggested supplements per references: Calcium c vitamin D 1200mg, Iron, MVI with zinc/selenium
Also if duodenal switch, add Vitamin A and Vitamin D3 1200units daily or 50,000 units weeekly

Supplements:
Roux-en-Y: MVI 200%, Calcium 1500-2000mg, Fe at least 18-27mg/day, B complex (optional)
Gastric Band: MVI, Calcium, B complex (optional)
Biliopancreatic/duodenal switch: MVI, ADEK: A 10,000 IU, D 2000 IU, K 300 mcg, Calcium, Fe, B complex

  • –NASPGHAN 2011:

Bariatric surgery:
Complications from gastric band: food impaction, erosion (now banned in Finland!), band slippage, gastric volvulus, band too tight, port infection

Roux-y gastric bypass:
anastomotic leak 1.2%, anastomotic ulcers/stricture

If post-op pain: epigastric –>do EGD & if neg do ‘RUQ w/u’, RUQ –> check U/S, LFTs possibly CT
If post-op vomiting –>do EGD
If post-op nausea –>Rx PPI and EGD if not improving
Anastomotic stricture in stomach –>dilate to 10-12mm in 1 session

  • -NEJM 2009; 361: 445/520. perioperative safety.
  • -NEJM 2007; 357: 741, 753, 818. Bariatric surgery improves mortality rate.
  • -NEJM 2007; 356: 2176. Review
  • -Gastro 2006; 130: 1848, 1564, 1617. Bariatric surgery frequently improves steatosis/NAFLD. Less improvement if ongoing insulin resistance.
  • -J Pediatr 2005; 147: 10-19. Review of bariatric surgery. suggests gastric bypass/gastric banding for adolescents.
  • -Pediatrics 2004; 114: 217-23, & 252, 253, 255. Consensus panel recommendations and commentary.

Note: Medication dosages should be checked in standard references for individual patients.  The blog may have transcription errors with regard to dosages listed with references.

Skipping breakfast –boomerang effect for obesity

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A recent article shows unfavorable biochemical variables associated with skipping breakfast in obese children and adolescents (J Pediatr 2012; 161: 871-4).

After recruiting 174 Brazilian subjects (6-16 years) through advertising, the investigators assessed their body composition with dual-energy-dray adsorptiometry and assessed fasting blood glucose and lipid profiles.  Face-to-face interviews with parents determined the frequency of skipped meals.  The median BMI in the cohort was 27.

Results:

  • Skipping breakfast was commonplace.  Only 46% of subjects consumed breakfast daily.  Skipping lunch or dinner was infrequent, approximately 10% and 22% at times skipped lunch and dinner respectively.
  • Consumption of breakfast was inversely correlated with the odds of obesity (OR 0.73).
  • Skipping breakfast was correlated with increased glucose, triglycerides, and very low density lipoprotein cholesterol.

The authors speculate that a prolonged period of fasting in the morning could affect ghrelin secretion which promotes increased food intake.  In addition, ghrelin could affect pancreatic insulin secretion.

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Dietary supplements — safe and effective?

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Most people consider dietary supplements as likely to be beneficial but at the very least ‘there not going to make you worse.’  That sentiment is wrong.  A review recently published has shown that some dietary supplements may increase the risk of cancer (Journal of the National Cancer Institute 2012; 104: 732-39).

Nearly half of the US adult population uses one or more dietary supplements but there is very little evidence that these supplements reduce cancer risk; in fact, the contrary is true.  Based on numerous studies, the authors make extensive comments regarding the studies of antioxidants, folic acid, and vitamin D/calcium which are summarized below.

Antioxidants

While observational data has suggested benefits from fruit and vegetable consumption, data on antioxidant supplement consumption has not shown a beneficial effect.  The review highlights a number of studies with regard to β-carotene, vitamin A, vitamin C, and vitamin E/α-tocopherol.  Specifically, vitamin C and E do not protect against total cancer incidence. α-tocopherol and β-carotene do not protect against cancer or cancer mortality.

  • The Selenium and Vitamin E Cancer Prevention Trial (SELECT) followed 35,533 men at average risk for prostate cancer for approximately 5.5 years.  This study was halted due to lack of benefit.  In addition, the extended followup reported that α-tocopherol significantly increased the risk of prostate cancer by 17%.
  • The β-carotene and Retinol Efficacy Trial (CARET) had a 39% increase in lung cancer incidence compared to the placebo arm.
  • In two of three large studies of β-carotene, the intervention increased the risk of all-cause mortality.
  • The Nutritional Prevention of Cancer (NPC) extended followup found that selenium supplementation statistically increased the risk of squamous cell skin cancer by 25% and non-melanoma skin cancer by 17%.

Folic Acid

Folic acid which is a synthetic oxidized form of folate is commonly used in fortification and supplements.  Recent meta-analysis of randomized controlled trials (RCTs) has found no effect of folic acid supplementation on the risk of colorectal adenomas over a 3-year treatment period.  In addition, one study demonstrated an increased risk of advanced colorectal adenomas (relative risk = 1.67).  Also, in observational studies, higher intake of folic acid has been linked with increased prostate cancer risk.

Vitamin D and Calcium

The Institute of Medicine published recommendations with regard to Vitamin D and calcium intake in 2011 and found that “there is not enough evidence to state that there is a causal association between low vitamin D intake and increased cancer risk.”  The authors summarize several conflicting results with regard to breast, colorectal, and prostate cancers. In addition, a recent meta-analysis of RCTs indicated that calcium supplementation was associated with a statistically-increased myocardial infarction risk.

Why are supplements so widespread if they are not beneficial and potentially dangerous?

  • The authors also summarize regulatory efforts.  In 1990, due to unsubstantiated health claims by food manufacturers, Congress passed the Nutrition Labeling Education Act (NLEA).
  • To limit FDA authority over supplements, at the behest of nutritional supplement manufacturers, in 1994 Congress passed the Dietary Supplement Health and Education Act.  This classified supplements as food and limited the role for the FDA.
  • In 2006, in reaction to deaths from ephedra, Congress passed the Dietary Supplement and Non-prescription Drug Consumer Protection Act.  This allows the FDA to collect adverse reports on supplements but did not give additional regulatory powers.

Conclusions from this review

  1. In populations with a high background of normal nutrient status, risk is accentuated if there can be harm at higher doses.  For selenium (in the NPC study), apparent benefits have been confined to individuals with the lowest baseline blood selenium levels.
  2. It is not reasonable to assume that consumption of a single nutrient would exert a chemopreventive effect equally in all tissues.  In addition, there are substantial variations in formulations and doses of supplements available.
  3. Efficacy and harm are typically tested over several years.  Given the natural history of cancer, it may take decades to assess supplement impact.
  4. Multiple consensus recommendations have indicated that supplements do not prevent cancer and do not prevent chronic disease (Table 1 in reference).  The most recent was from the American Cancer Society in 2012. “Present knowledge indicates that dietary supplements do not lower cancer risk.”
  5. Despite the evidence, the authors note that believers in supplements are unlikely to accept ‘mainstream’ science.  Some may think that unconventional treatments are ignored by science for monetary reasons. Some may think that these products are regulated and would not be offered if they were not beneficial.

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common to be “d-ficient” | gutsandgrowth

Two new drugs for obesity

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Undoubtedly, a safe, effective medication for obesity would be a pharmaceutical blockbuster.  The record so far on previous medications has been dismal.  Many have been abandoned due to safety concerns, including sibutramine (myocardial infarction and stroke) as well as dexfenfluramine/fenfluramine (valvulopathy).  Two new FDA-approved agents have shown promise but caution in their use will be needed (NEJM 2012; 367: 1577-79).  Neither agent has approval for pediatric usage.

Belviq (lorcaserin) is a selective agonist of the serotonin 5-HT-2C receptor and Qsymia (phentermine with topiramate) is a combination sympathomimetic amine (anorectic agent) with an antiepileptic drug.

In studies with lorcaserin, three studies (1-year placebo-controlled) have shown that the number of patients losing >5% of body weight was increased compared to placebo.  Mean percentage body weight loss with lorcaserin was -5.8% in first two studies and -4.5% in third study.  In contrast, placebo patients who received lifestyle counseling lost  -2.5% and -1.5% respectively.  Overall, up to 47% of patients receiving medication lost more than 5% body weight.

Potential safety concerns with lorcaserin:  initially there were concerns due to increased incidence of tumors in rats and possible valvulopathy (eg. mitral or aortic valve regurgitation).  However, the FDA has concluded that it is unlikely that these are likely to occur in humans.

With phentermine/topiramate, two placebo-controlled studies have shown an increase in patients losing >5% of body weight compared to placebo.  In the first study, the mean percentage change in body weight was -10.9% combination (dosage 15 mg/92 mg) compared with -1.6% for placebo.  In the second study, this dosage led to a -9.8% reduction compared with -1.2% in placebo patients. Overall, up to 70% of patients receiving medication lost more than 5% body weight.

With regard to safety, it is known that topiramate is teratogenic and increases the risk of orofacial cleft.  Due to this, approval for this combination requires a risk evaluation and mitigation strategy (REMS) which permits only specially-certified pharmacies to dispense along with formal training for prescribers. In addition, this combination has been associated with mildly increased heart rate. Due to favorable changes in blood pressure, the FDA concluded that this medication had a good benefit-risk balance.  But, the manufacturer recommends against it use in patients with cardiac issues or cerebrovascular disease.

With both new medications, other safety concerns include the risk of increased psychiatric effects.  In addition, specific recommendations include the following:

  • Only recommended in adults with BMI ≥30 or adults with BMI ≥27 with at least one weight-related comorbidity
  • With both medications, if weight loss not adequate after 12 weeks then discontinue medication.  With lorcaserin, if weight loss is not ≥5%, then discontinue.  With phentermine/topiramate, if weight loss is not ≥3% at 12 weeks (with 7.5 mg/46 mg), consider dosage increase and/or discontinuation.

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Brain and body benefits of chocolate?

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Chocolate has been receiving a lot of good press, including purported benefits in weight loss (Arch Intern Med 2012;172:519-521.) and now for cognitive function (NEJM 2012; 367: 1562-64).

The first article looked at the chocolate consumption of 975 subjects who completed food frequency questionnaires.  The mean age of these participants was 57 years.  “After controlling for multiple potential confounders including sex, physical activity, fruit and vegetable intake, depression, and total caloric intake, frequency of chocolate consumption continued to be associated with lower BMI.”

The second study shows a correlation with a countries’ annual per capita chocolate consumption and the number of Nobel laureates per 10 million population.  The highest per capita rate of Nobel prizes is in Switzerland!  The author notes that cocoa and other flavonols seem to be effective in slowing or reversing reductions in cognitive performance that occurs with aging and have other potential benefits.  One of the limitations in the author’s analysis included reverse causation —that is enhanced cognitive performance could stimulate more countrywide chocolate consumption.  This seems more plausible to me.  Fortunately for readers of this intriguing study, the author did provide a relevant disclosure: “Dr. Meserli reports regular daily chocolate consumption, mostly…Lindt’s dark varieties.”

Six years later-Mediterranean diet comes out on top

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This month a followup letter provides long-term data on the outcomes of individuals assigned to either a low-carb, low-fat, or Mediterranean diet (NEJM 2012; 1373-74).

An initial study posted two-year results.  Now after an additional four years, the following results were noted:

  • Among the 259 participants (80% of original groups and 95% who completed the initial two years), 67% had continued their original assigned diet.
  • For the entire 6-year period, the total weight loss was 3.1 kg in the Mediterranean group, 1.7 kg in the low-carb group and 0.6 kg in the low-fat group.
  • At 6 years the change in the ratio of LDL to HDL were similar in all three groups though the low-carb group had the most favorable results with a reduction of 0.16.
  • At 6 years, the reduction in triglyceride levels from baseline were significant for the Mediterranean group (21.4 mg/dL) and the low-carb group (11.3 mg/dL).
  • All of the groups had regained some of their weight loss from the initial 2-year period.  The most favorable outcomes were noted in the Mediterranean diet and then the low-carb diet in this workplace intervention trial.

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