Decreasing FODMAPs Intake by Switching to Sourdough Bread

The fructans content of sourdough bread was found to be, on average, 72% lower than that of bread made with baker’s yeast. This reduction in fructans content appeared to be due to the degradation of fructans by an enzyme produced by the lactic acid bacteria that are used to make sourdough bread. The fructans concentration in sourdough bread was below the cut-off level (< 0.3 g of oligosaccharides per serving of grains or cereal) that is used to allow the food to be consumed as part of a low-FODMAPs diet.

Comment: “FODMAPs” is an acronym for Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols. Many people with irritable bowel syndrome (IBS) do not tolerate foods that contain large amounts of these compounds, and low-FODMAPs diets have been used successfully to treat IBS. Fructans are fermentable oligosaccharides that consist of polymers of fructose molecules. The two main categories of fructans in foods are fructooligosaccharides and inulin. Wheat contains a relatively high concentration of fructans, and wheat intake is restricted on a low-FODMAPs diet.

Most leavened breads use baker’s yeast to make the dough rise. In contrast, the production of sourdough bread involves fermentation by “wild yeast” and lactic acid bacteria that are naturally present in flour. The results of the present study indicate that sourdough bread has a low concentration of fructans, and may therefore be an acceptable alternative to bread made with baker’s yeast for patients with IBS who are on a low-FODMAPs diet.

Intolerance to fructans is not the only mechanism by which wheat consumption triggers gastrointestinal symptoms. In some cases, the symptoms appear to result from an allergic reaction to one or more of the proteins present in wheat. In those cases, people would likely develop symptoms from sourdough bread.

Menezes LA, et al. Reducing FODMAPs and improving bread quality using type II sourdough with selected starter cultures. Int J Food Sci Nutr. 2021;72::912-922.

Magnesium for Nocturnal Leg Cramps

One hundred eighty-four Ukranian individuals (mean age, 57 years) with nocturnal leg cramps were randomly assigned to receive, in double-blind fashion, 226 mg of magnesium (as magnesium oxide monohydrate) once a day at bedtime or placebo for 60 days. The mean number of nocturnal leg cramps per week decreased by 63% (p < 0.001) in the magnesium group, from 5.4 at baseline to 2.0 at the end of the study. This improvement was significantly greater (p = 0.01) than the 41% decrease in the placebo group. Compared with placebo, magnesium treatment also resulted in a greater decrease in the duration of nocturnal leg cramps (p < 0.007) and greater improvement in sleep quality (p < 0.001).

Comment: Nocturnal leg cramps are a common problem, particularly among elderly people. In most cases, a cause cannot be identified. The results of the present study indicate that magnesium is an effective treatment for nocturnal leg cramps. Magnesium has an antispasmodic effect, which may explain its mechanism of action. The dosage of magnesium used in this study (elemental magnesium versus magnesium oxide monohydrate) was clarified in a personal communication with one of the researchers.

Barna O, et al. A randomized, double-blind, placebo-controlled, multicenter study assessing the efficacy of magnesium oxide monohydrate in the treatment of nocturnal leg cramps. Nutr J. 2021;20:90.

Adverse Reactions to Alpha-Lipoic Acid

Suspected adverse reactions to alpha-lipoic acid (ALA)-containing products were identified from the Italian Phytovigilance System. From March 2002 to February 2020, 116 reports concerning 212 adverse reactions were identified. Skin conditions (44.9%) and gastrointestinal disorders (10.8%) were the most frequent reactions. Causality was considered definite in 15 cases, probable in 35, possible in two, unlikely in five, and unclassifiable in 37. Ten people developed insulin autoimmune syndrome, a potentially serious condition. The likelihood that this condition was caused by ALA was considered definite in one case, probable in eight, and possible in one. Insulin autoimmune syndrome is characterized by transient hypoglycemia, the presence of anti-insulin antibodies in serum, and very high serum concentrations of insulin during hypoglycemic attacks. It has been suggested that ALA might bind to insulin and thereby increase its antigenicity.

Comment: ALA has generally been considered safe with few side effects reported at usual therapeutic doses. Allergic skin reactions and gastrointestinal symptoms have previously been reported but I have not seen previous reports of insulin autoimmune syndrome. While side effects of ALA are uncommon, practitioners should consider adverse reactions to ALA in the differential diagnosis of the conditions described in this report.

Gatti M, et al. Assessment of adverse reactions to alpha-lipoic acid containing dietary supplements through spontaneous reporting systems. Clin Nutr. 2021;40:1176-1185.

Can Increasing Fiber Intake Help You Lose Weight?

Two hundred forty-two overweight or obese men and women (aged 30-70 years; body mass index, 27-35 kg/m²) were randomly assigned to consume high-fiber rye products or refined wheat products for 12 weeks. All participants were prescribed a low-calorie diet and were advised to minimize intake of sugar and fast food, increase intake of vegetables, and decrease portion size. After 12 weeks, mean body weight fell to a greater extent in the group consuming rye than in the group consuming refined wheat (2.86 kg vs. by 1.79 kg; p < 0.004). Mean loss of body fat was also greater in the rye group than in the refined-wheat group (p = 0.03). Daily energy intake decreased from baseline to week 12 by 172 kcal in the rye group and by 92 kcal in the refined-wheat group.

Comment: Among whole grains, rye is the richest source of dietary fiber. Consuming a high-fiber diet may help prevent or reverse obesity by several different mechanisms. First, high-fiber foods tend to have low caloric density. Second, such foods require additional chewing, which slows the rate at which a person eats. Third, fiber holds water and thereby promotes a feeling of fullness and satiety. In this study, compared with a diet containing low-fiber refined wheat, a diet containing high-fiber rye products decreased total energy intake and enhanced weight loss in overweight and obese individuals who were trying to lose weight.

Iversen KN, et al. A hypocaloric diet rich in high fiber rye foods causes greater reduction in body weight and body fat than a diet rich in refined wheat: A parallel randomized controlled trial in adults with overweight and obesity (the RyeWeight study). Clin Nutr ESPEN. 2021;45:155-169.

Beneficial Effect of Mediterranean Diet and Mindfulness-Based Stress Reduction During Pregnancy

Pregnant women (n = 1,221) in Barcelona, Spain, who were between 19 and 23 weeks of gestation and considered at high risk of having a small-for-gestational-age (SGA) baby were randomly assigned to consume a Mediterranean diet, to participate in a mindfulness-based stress-reduction program, or to receive usual care (control group). Participants in the Mediterranean diet group received two hours per month of individual and group educational sessions and free extra-virgin olive oil and walnuts. Women in the stress reduction group underwent an eight-week program consisting of weekly 2.5-hour sessions and one full-day session. SGA (the primary outcome measure) was defined as birth weight below the 10th percentile. SGA occurred in 21.9% of infants in the control group, 14.0% of infants in the Mediterranean diet group (p = 0.004 vs. control group), and 15.6% of infants in the stress reduction group (p = 0.02 vs. control group). The secondary outcome measure was a composite of at least one of the following: preterm birth, preeclampsia, perinatal mortality, severe SGA, neonatal acidosis, low Apgar score, or presence of any major neonatal morbidity. The secondary outcome occurred in 26.2% of participants in the control group, 18.6% in the Mediterranean diet group (p = 0.01 vs. control group) and 19.5% in the stress reduction group (p = 0.02 vs. control group).

Comment: Being born SGA is a leading cause of perinatal morbidity and mortality. Maternal suboptimal nutrition and high stress levels have been associated with poor fetal growth and adverse pregnancy outcomes. In the present study of pregnant women at high risk of having an SGA baby, treatment with a Mediterranean diet or with mindfulness-based stress reduction, compared with usual care, significantly reduced the percentage of newborns with birth weight below the 10th percentile.

Crovetto F, et al. Effects of Mediterranean diet or mindfulness-based stress reduction on prevention of small-for-gestational age birth weights in newborns born to at-risk pregnant individuals: the IMPACT BCN randomized clinical trial. JAMA. 2021;326:2150-2160.

Consumption of Ultraprocessed Foods Is Increasing

Consumption of ultraprocessed foods among US children aged 2-19 years (mean, 10.9 years) was examined over 10 cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999-2000 to 2017-2018. Ultraprocessed food was defined as food produced from a series of industrial processes. Ingredients characteristic of ultraprocessed foods include high-fructose corn syrup, hydrogenated oils, flavor enhancers, colors, and emulsifiers. Examples of ultraprocessed foods include sweet or savory packaged snacks, sugar-sweetened beverages, candy, industrial bread, industrial breakfast cereal, ready-to-heat-and-eat pasta dishes and pizza, and sausages and other reconstituted meat products. From 1999 to 2018, the estimated percentage of total energy consumed from ultraprocessed foods increased from 61.4% to 67.0% (p for trend < 0.001), whereas the percentage of total energy consumed from unprocessed or minimally processed foods decreased from 28.8% to 23.5% (p for trend < 0.001).

Comment: Studies have shown that consumption of ultraprocessed foods is associated with higher total caloric intake and may promote the development of obesity. Observational studies have found that higher intake of ultraprocessed foods is associated with increased risk of cardiovascular disease and cerebrovascular disease, even after adjusting for other dietary factors such as intake of saturated fat, sodium, sugar, and fiber. The trend toward increasing consumption of these types of foods is worrisome, in that it may portend an increasing burden of chronic disease in our society.

Wang L, et al. Trends in consumption of ultraprocessed foods among US youths aged 2-19 years, 1999-2018. JAMA. 2021;326:519-530.

Can Eating Olive Oil Prolong Your Life?

The association between consumption of olive oil and total and cause-specific mortality was examined in prospective cohort studies of 60,582 US women participating in the Nurses’ Health Study (1990-2018) and 31,801 men participating in the Health Professionals Follow-up Study (1990-2018) who were free of cardiovascular disease and cancer at baseline. Diet was assessed by a food-frequency questionnaire every four years. During 28 years of follow-up, 36,856 deaths occurred. After adjustment for potential confounding variables including age; ethnicity; marital status; cigarette and alcohol use; physical activity; family history of diabetes, cancer, and myocardial infarction; history of hypertension and hypercholesterolemia; use of multivitamins; body mass index; total energy intake; and intake of red meat, fruits, vegetables, nuts, whole grains, and soda, the pooled hazard ratio (HR) for all-cause mortality among participants who had the highest consumption of olive oil (more than 0.5 tablespoon per day or more than 7 g per day), as compared with those who never or rarely consumed olive oil, was 0.81 (95% confidence interval [CI], 0.78-0.84). Higher olive oil intake was associated with a 19% lower risk of cardiovascular disease mortality (HR = 0.81; 95% CI, 0.75-0.87), a 17% lower risk of cancer mortality (HR = 0.83; 95% CI, 0.78-0.89), a 29% lower risk of neurodegenerative disease mortality (HR = 0.71; 95% CI, 0.64-0.78), and an 18% lower risk of respiratory disease mortality (HR = 0.82; 95% CI, 0.72-0.93). In substitution analyses, replacing 10 g per day of margarine, butter, mayonnaise, and dairy fat with the equivalent amount of olive oil was associated with an 8%-34% lower risk of total and cause-specific mortality.

Comment: In this prospective cohort study, olive oil consumption was associated with a lower risk of all-cause mortality, as well as a lower risk of death due to cardiovascular disease, cancer, neurodegenerative disease, and respiratory disease. While observational studies cannot prove causation, the possible protective role of olive oil is biologically plausible. As compared with oils such as corn oil, soybean oil, and safflower oil, olive oil has a higher concentration of monounsaturated fatty acids and a lower concentration of polyunsaturated fatty acids. Olive oil is therefore less likely to form potentially toxic lipid peroxides during cooking. Lipid peroxides may play a role in the pathogenesis of most, if not all, of the diseases mentioned above. In addition, unrefined (extra virgin) olive oil contains compounds that have anti-inflammatory activity. Unrefined olive oil might therefore help prevent the development or progression of diseases that have an inflammatory component.

Guasch-Ferre M, et al. Consumption of olive oil and risk of total and cause-specific mortality among U.S. adults. J Am Coll Cardiol. 2022;79:101-112.

Iron Supplementation for Postpartum Depression or More Iranian Research Fraud?

Seventy Iranian women (mean age, 32 years) with postpartum depression on day 7 after delivery and a median serum ferritin level of 24 mg/dl were randomly assigned to receive, in double-blind fashion, 50 mg per day of iron or placebo for six weeks. The median score on the Edinburgh Postnatal Depression Scale improved significantly by 25% (p < 0.001) in the iron group and improved nonsignificantly by 8% in the placebo group (p < 0.05 for the difference in the change between groups). These results indicate that iron supplementation improved postpartum depression in Iranian women, many of whom had low or borderline-low iron status.

Comment: When I first read this paper (published online in 2015), I was not fully aware of what appears to be an epidemic of fraudulent research coming from Iran. I even cited this research in the second edition of my textbook, Nutritional Medicine. I recently took a closer look at this paper and discovered a number of issues that cause me to doubt its credibility.

1.Impossible or implausible timing: The paper stated that at 1 week postpartum the mothers were randomly assigned to receive iron or placebo. However, in the Methods section of the paper, it was stated that at 1 week postpartum the mothers were contacted by phone and invited to participate in the study. Those who agreed to participate were asked to complete the Edinburgh Postnatal Depression Scale. Mothers who had a score of 11 or higher were interviewed by a psychiatrist to confirm the diagnosis of postpartum depression. The procedures described in the Methods section – being home to receive the phone call, filling out the questionnaire, returning the questionnaire, having the questionnaire analyzed, scheduling an appointment with the psychiatrist, and seeing the psychiatrist – all take time. It is therefore virtually impossible that the women could have been started on iron or placebo on the same day they were first contacted by phone and invited to participate.

The paper also stated that the women were reevaluated at 7 weeks postpartum, which was after they had received iron or placebo for 6 weeks. However, this reevaluation could only have occurred at 7 weeks postpartum if the treatment was started at 1 week postpartum (which, as discussed above, was virtually impossible).

2. Discrepancy regarding timing: The Iranian Registry of Clinical Trials (IRCT) document that is connected to this study stated that hemoglobin and hematocrit will be measured during hospitalization, at the time of hospital discharge after delivery, and 1 month later. However, according to the paper, hemoglobin was measured seven days after delivery and six weeks later.

3. Discrepancies regarding inclusion criteria: The IRCT document stated that women had to be 15 to 49 years of age to participate. The paper stated that women had to be 20 to 40 years of age. The IRCT document stated that all postpartum mothers were eligible to participate. The paper stated that mothers were eligible if they had delivered a healthy term infant through an uncomplicated elective cesarean section and did not have any medical illness.

4. Discrepancies regarding exclusion criteria: The IRCT document stated that women were excluded if they had thalassemia or a hemoglobin level below 10.5. The paper listed additional exclusion criteria, such as a history of any psychiatric disorder before or during pregnancy, any medical illness upon enrollment, or a family history of psychiatric disorders.

5. Discrepancy regarding the treatment: The IRCT document stated that women received 30 mg of ferrous sulfate daily for 1 month. It was not stated whether this dose referred to 30 mg of elemental iron or to 30 mg of ferrous sulfate (which would be equivalent to 6.0 mg or 11.1 mg of elemental iron, depending on whether the ferrous sulfate was desiccated or hydrated). The paper stated that the women received 50 mg of elemental iron from ferrous sulfate daily for six weeks.

6. Discrepancy regarding the method of assessment: The IRCT document stated that depression would be assessed by both the Beck and Edinberg’s questionnaires. In the paper, only the Edinburgh Postnatal Depression Scale was used.

7. Improper reporting of units: The paper used mg/dl as the unit for serum ferritin, with a cutoff level of less than 15 for iron deficiency. However, the typical unit for ferritin is µg/L or ng/ml. Using mg/dl as the unit of measurement, the cutoff level for iron deficiency should have been 0.15, not 15. The paper also used a hemoglobin level of less than 10.5 mg/dl as the cutoff level for anemia. However, hemoglobin is typically measured in g/dl. Using mg/dl as the unit of measurement, the cutoff level for anemia should have been 10,500 mg/dl, not 10.5 mg/dl.

Sheikh M, et al. The efficacy of early iron supplementation on postpartum depression, a randomized double-blind placebo-controlled trial. Eur J Nutr. 2017;56:901-908.