Alan R. Gaby, MD
Is Food Allergy Testing Reliable?
Fifty-six patients with eosinophilic esophagitis underwent a six-food elimination diet. A response to the diet was defined as less than 15 eosinophils per high-power field (HPF) in esophageal biopsy samples, and a positive reaction on individual food challenges was defined as greater than 15 eosinophils per HPF. Twenty-nine patients responded to the diet and 23 completed the individual food challenges. Food triggers were identified in 20 patients, the most common being wheat (n = 10), milk (n = 9), and egg (n = 8). Five different allergy tests: skin-prick and skin-patch tests, serum allergen-specific IgE, basophil activation test, and serum food-specific IgG were performed prior to the commencement of the diet. None of these tests accurately predicted food triggers. Patch testing was always negative for foods. Serum IgG levels to food antigens were positive to two or more foods in all cases, but there was no correlation with actual food triggers. Serum IgG levels accurately predicted an individual food trigger in 13 of 20 patients, missed a food trigger in 11 of 20, and led to an over-restrictive diet in 19 of 20 patients.
Comment: The results of this study indicate that various commonly used allergy tests cannot accurately predict food triggers in patients with eosinophilic esophagitis. Food elimination and rechallenge in association with esophageal histological assessment is currently the only diagnostic method that has been demonstrated to be reliable for patients with eosinophilic esophagitis. The findings from this study do not necessarily apply to other conditions that have a food allergy component, such as migraines, rheumatoid arthritis, attention deficit-hyperactivity disorder, or inflammatory bowel disease, because the immunological mechanisms underlying those diseases may differ from those in eosinophilic esophagitis. However, I am not aware of any convincing evidence that the tests examined in this study are useful for identifying “hidden” (non-IgE-mediated) allergies. In my experience, an elimination diet followed by individual food challenges is the most reliable diagnostic method.
Philpott H, et al. Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis. A comprehensive prospective study using five modalities. Aliment Pharmacol Ther. 2016;44:223-233.
Preoperative Intravenous Iron for Iron-Deficient Surgical Patients
Seventy-two patients with iron-deficiency anemia who were scheduled to undergo major abdominal surgery were randomly assigned to receive preoperative intravenous iron or usual care (control group). Anemia was defined as a hemoglobin level below 12.0 g/dl for women and below 13.0 g/dl for men. Iron deficiency was defined as a serum ferritin level less than 300 µg/L and transferrin saturation less than 25%. Patients in the iron group received intravenous ferric carboxymaltose as a single dose (15 mg/kg of body weight, to a maximum of 1,000 mg) over 15 minutes. They also received postoperatively, within two days of surgery, 0.5 mg of ferric carboxymaltose per recorded 1 ml of blood loss, if blood loss was at least 100 ml. The proportion of patients who required a blood transfusion before or after surgery was 60% lower in the iron group than the control group (12.5% vs. 31.3%; p < 0.08). Median length of hospital stay was 33% lower in the iron group than in the control group (6 vs. 9 days; p < 0.05).
Comment: This study suggests that intravenous administration of iron in the perioperative period can decrease the length of hospital stay and possibly decrease the need for blood transfusions in patients with iron-deficiency anemia who are scheduled to undergo major abdominal surgery. Iron supplementation presumably works by enhancing the capacity of the body to produce new red blood cells. The cut-off point for serum ferritin that was used to diagnose iron deficiency was much higher than the usual reference range. The higher value was presumably used because serum ferritin levels rise in response to inflammation, and many conditions for which major abdominal surgery are indicated are associated with chronic inflammation.
Froessler B, et al. The important role for intravenous iron in perioperative patient blood management in major abdominal surgery: a randomized controlled trial. Ann Surg. 2016;264:41-46.
Probiotic Prevents Infectious Mastitis in Nursing Mothers
One hundred eight pregnant women who had experienced infectious mastitis after previous pregnancies were randomly assigned to receive, in double-blind fashion, a probiotic preparation (Lactobacillus salivarius PS2; 9 log10 colony-forming units once a day) or placebo, from about 30 weeks of gestation until delivery. The proportion of women who developed infectious mastitis during the first three months after delivery was significantly lower in the probiotic group than in the placebo group (25% vs. 57%; p = 0.001). When mastitis occurred, the milk bacterial counts were significantly lower in the probiotic group than in the placebo group.
Comment: Mastitis is a common problem in breastfeeding women. It is frequently caused by an infection with Staphylococcus aureus or other bacteria. Conventional treatment includes antibiotics, pain medication, hot packs before feeding, and cold packs after feeding. The results of the present study indicate that administration of L. salivarius PS2 during late pregnancy can decrease the incidence and severity of infectious mastitis in women who have suffered from this problem in a previous pregnancy. Further research is needed to determine whether other probiotic strains would have a similar effect.
Fernandez L, et al. Prevention of infectious mastitis by oral administration of Lactobacillus salivarius PS2 during late pregnancy. Clin Infect Dis. 2016;62:568-573.
Riboflavin for Cyclic Vomiting Syndrome
Three children with cyclic vomiting syndrome experienced marked improvement or complete resolution of symptoms after starting riboflavin supplements. One patient had a complete response to 10 mg per day of riboflavin. In the other two patients, 400 mg per day appeared to be more effective than 20-30 mg twice a day.
Comment: Cyclic vomiting syndrome is a condition that occurs mainly in children and is characterized by repeated rapid-fire episodes of vomiting separated by symptom-free intervals. It is associated with mitochondrial dysfunction and migraines (some consider it to be a migraine variant). Mitochondrial energy production appears to be impaired in people with cyclic vomiting syndrome. In addition to riboflavin, L-carnitine and coenzyme Q10 (alone or in combination) have been reported to be beneficial for children with this condition. Of note, each of these three nutrients plays a role in mitochondrial energy production. That observation raises the possibility that other nutrients involved in mitochondrial energy production, such as iron (if deficient) and magnesium, might also be effective.
Martinez-Esteve Melnikova A, et al. Riboflavin in cyclic vomiting syndrome: efficacy in three children. Eur J Pediatr. 2016;175:131-135.
Gluten-Free Diet for Nephrotic Syndrome
Eight children with difficult-to-manage nephrotic syndrome (i.e., glucocorticoid sensitive with a glucocorticoid-dependent or frequently relapsing pattern, or glucocorticoid resistant) were treated with a gluten-free diet, beginning at 2-14 years of age and continuing for a mean duration of 3.4 years (range, 0.6-14 years). All patients had clinical improvement, enabling reduction or discontinuation of glucocorticoids.
Comment: Nephrotic syndrome is a kidney disease characterized by proteinuria, hypoalbuminemia, edema, and hypercholesterolemia. Glucocorticoids are the mainstay of conventional therapy in most cases. While glucocorticoids have significantly reduced the mortality rate in patients with nephrotic syndrome, these drugs have numerous adverse effects. In previous studies, food allergy was found to be a frequent cause or exacerbating factor in children, and to a lesser extent in adults, with nephrotic syndrome. Cow’s milk was the most commonly implicated food, but other allergens such as wheat, gluten, egg, pork, fish, beef, and chicken were involved in some cases. The results of the present study confirm the importance of food sensitivity in some children with nephrotic syndrome.
Lemley KV, et al. The effect of a gluten-free diet in children with difficult-to-manage nephrotic syndrome. Pediatrics. 2016;138:e20154528.
FODMAPs and Irritable Bowel Syndrome
Eighty-seven individuals (mean age, 43 years) with irritable bowel syndrome (IBS) were randomly assigned to consume, in double-blind fashion, regular sourdough rye bread or sourdough rye bread low in FODMAPs for four weeks. After a washout period of at least four weeks, each person consumed the alternate bread for an additional four weeks. During the first week of each treatment period, subjects consumed 3.5 to 4 slices of bread per day; and during weeks two to four, they consumed 7 to 8 slices per day. The low FODMAPs bread was produced using a Lactobacillus strain that efficiently consumed fructans and prevented mannitol accumulation during proofing. The fiber content of the breads was similar. The mean weekly total IBS symptom score (on a scale of 0-100, with 100 indicating the worst symptoms) was significantly lower with the low-FODMAPs bread than with the regular bread (30 vs. 33; p = 0.02). Specific symptoms that were significantly lower with low-FODMAPs bread than with control bread were flatulence, abdominal pain, intestinal cramps, and stomach rumbling. The breath hydrogen concentration was significantly lower (indicating less carbohydrate malabsorption) with low-FODMAPs bread than with control bread.
Comment: “FODMAPs” is an acronym for fermentable oligosaccharides, disaccharides, monosaccharides, and polyols. FODMAPs include fructose, lactose, sorbitol, mannitol, fructans (fructooligosaccharides, inulin), and galactans (also called galactooligosaccharides; e.g., raffinose). Foods restricted on a low-FODMAPs diet include lactose-containing foods, foods with added fructose, foods which naturally contain fructose in excess of glucose (e.g., apples, pears), fructan-containing foods (e.g., wheat, rye, artichokes, onions, garlic, leeks), sorbitol-containing foods (e.g., stone fruits), and raffinose-containing foods (e.g., legumes, lentils, cabbage, and Brussels sprouts). In several clinical trials, consumption of a low-FODMAPs diet improved symptoms in patients with IBS. It was not always possible in these studies to determine whether the benefit was due to a reduction in FODMAPs consumption or to the avoidance of a common allergen such as wheat. The results of the present study appear to confirm that at least some of the benefit of a low-FODMAPs diet is due to a decrease in FODMAPs intake per se. The beneficial effect in this study was only modest, but no attempt was made to make comprehensive dietary changes that would have decreased FODMAPs intake to a greater extent.
Laatikainen R, et al. Randomised clinical trial: low-FODMAP rye bread vs. regular rye bread to relieve the symptoms of irritable bowel syndrome. Aliment Pharmacol Ther. 2016;44:460-470.
Vitamin D and Falls: Dosage Regimen Matters
Two hundred men and women (mean age, 78 years) with a prior fall and a mean serum 25-hydroxyvitamin D (25[OH]D) level of 19.3 ng/ml were randomly assigned to receive, in double-blind fashion, 24,000 IU of vitamin D3 once a month, 60,000 IU of vitamin D3 once a month, or 24,000 IU of vitamin D3 plus 300 µg of calcifediol (25-hydroxyvitamin D) once a month for 1 year. At baseline, 58% of the participants had a 25(OH)D level below 20 ng/ml. The proportion of participants who fell at least once during the study was significantly higher with high-dose vitamin D and with low-dose vitamin D plus calcifediol than with low-dose vitamin D.
Comment: Vitamin D plays a role in neuromuscular function. In some, but not, all studies supplementation of elderly individuals with vitamin D decreased the incidence of falls, presumably by improving muscle strength and balance. However, in one study, administration of a very large dose of vitamin D (500,000 IU) once a year to elderly people for 3 to 5 years resulted in a significant increase in the number of falls compared with placebo. This excess number of falls was clustered mainly in the first three months after each vitamin D dose, which suggests that subtle vitamin D toxicity occurred transiently after each dose, possibly resulting in transient impairments of strength or balance. In the present study, the incidence of falls was greater with a monthly bolus of 60,000 IU of vitamin D (equivalent to about 2,000 IU per day) than with 24,000 IU (equivalent to about 800 IU per day). This adverse effect may have been due to the higher vitamin D dose per se (as opposed to the use of intermittent bolus doses). That possibility is supported by the results of a previous trial, in which there was a nonsignificant 30% increase in falls in elderly individuals who received 2,000 IU per day of vitamin D for 1 year than in those who received 800 IU per day (Bischoff-Ferrari HA, et al. Effect of high-dosage cholecalciferol and extended physiotherapy on complications after hip fracture: a randomized controlled trial. Arch Intern Med. 2010;170:813-820.)
Bischoff-Ferrari HA, et al. Monthly high-dose vitamin D treatment for the prevention of functional decline: a randomized clinical trial. JAMA Intern Med. 2016;176:175-183.
Melatonin Prevents Bone Loss
Eighty-one postmenopausal women (mean age, 63 years) with osteopenia were randomly assigned to receive, in double-blind fashion, melatonin (1 mg per day or 3 mg per day) or placebo at night for one year. Compared with placebo, 3 mg per day of melatonin increased mean bone mineral density (BMD) at the femoral neck by 2.3% (p < 0.01) and mean BMD at the lumbar spine by 3.6% (p = 0.04). The lower dose of melatonin produced only a small improvement in BMD compared with placebo that was not statistically significant.
Comment: These results suggest that supplementation with 3 mg per day of melatonin can help preserve BMD in postmenopausal women with osteopenia. The mechanism of action of melatonin is not known. Further research is needed to determine whether melatonin can prevent fractures.
Amstrup AK, et al. Melatonin improves bone mineral density at the femoral neck in postmenopausal women with osteopenia: a randomized controlled trial. J Pineal Res. 2015;59:221-229.
This column was originally published in Townsend Letter, January 2017.
Published January 27, 2024
About the Author
Alan R. Gaby, MD, is the author of the textbook, Nutritional Medicine, which is now in its third edition (doctorgaby.com). He received his undergraduate degree from Yale University, his M.S. in biochemistry from Emory University, and his M.D. from the University of Maryland. He was in private practice for 19 years, specializing in nutritional medicine. Over the past 43 years, Dr. Gaby has developed a computerized database of more than 29,000 individually chosen medical journal articles related to the field of natural medicine. He was professor of nutrition and a member of the clinical faculty at Bastyr University in Kenmore, Washington, from 1995 to 2002.
He is past president of the American Holistic Medical Association and gave expert testimony to the White House Commission on Complementary and Alternative Medicine on the cost-effectiveness of nutritional supplements. He is the author of Preventing and Reversing Osteoporosis (Prima, 1994), The Doctor’s Guide to Vitamin B6 (Rodale Press, 1984), and co-author of The Patient’s Book of Natural Healing (Prima, 1999). He was Chief Science Editor for Aisle 7 (formerly Healthnotes, Inc.) and has appeared on the CBS Evening News and the Donahue Show.