Hypophosphatemia with an Elemental Formula

A recent retrospective study (LF Gonzalez Ballesteros et al Bone 2017; 97: 287-92) of 17 centers in North America and Ireland (2014-2016) identified a frequent association between an elemental formula and idiopathic hypophosphatemia in infants and children.

Key findings:

  • “Fifty-one children were identified at 17 institutions with unexplaned hypophosphatemia.  Most children had complex illnesses and been solely fed Neocate® formula products for variable periods of time.”
  • “Hypophosphatemia was detected during evaluation of fractures or rickets.  Increased alkaline phosphatase activity”  was noted in nearly all cases.
  • “Most all improved with addition of supplemental phosphate or change to a different formula product.”
  • Median age was 3.0 years (range 0.2 years to 15.5 years).  Median duration of Neocate® was 1.3 years

Since the composition of the formula had adequate phosphate, the authors speculate that the “bioavailability of formula phosphorus may be impaired in certain clinical settings.” Interestingly, this report singles out Neocate® products, “although the possibility of hypophosphatemia may occur with other amino-acid based formulas cannot be excluded.” Neocate® infant has similar amounts of phosphorus as Elecare®: 82.2 mg of phosphorus per 100 kcal compared with 84.2 mg.

My take: In patients receiving exclusive amino-acid based formulas (especially Neocate®), it is probably worthwhile to periodically monitor phosphate, calcium, alkaline phosphatase and possibly other micronutrients.

College of Charleston

Vitamin D3 vs Vitamin D2

Vitamin D3 appears to be more effective at increasing vitamin D levels than vitamin D2 according to a recent study: From MedicalNewsToday: Vtiamin D Guidelines May Be Changing Following New Study

An excerpt:

The researchers measured vitamin D levels in 335 South Asian and white European women over two winter periods. They chose winter because, due to a reduction in sunlight exposure, vitamin D levels tend to be lower at this time.

The women were split into five groups: those consuming vitamin D-2 in a biscuit; those consuming vitamin D-3 in a biscuit; those consuming vitamin D-2 in a juice drink; those consuming vitamin D-3 in a juice drink; and those receiving a placebo.

The study found that vitamin D-3 was twice as effective at raising vitamin D levels in the body as vitamin D-2.

Participants who received the D-3 in a biscuit raised their levels of vitamin D by 74 percent, while those receiving the vitamin in juice saw a 75 percent increase. Those receiving D-2 had a 33 and 34 percent increase, respectively. The placebo group experienced a drop of 25 percent across the same period.

Related blog posts:

Better Diet, Lower Mortality

Nutrition science is hampered by the inability to randomize people into various treatment approaches.  Thus, when we see that some individuals who, for example, eat more fish, we are unable to conclude that the difference in their outcome is related to their diet or related to other factors that we cannot control.  It could be that individuals who eat fish may exercise more, have more money, smoke less or have less stress.

That being said, we can find associations that may be meaningful.  Into this mix, another study (M Sotos-Prieto et al. NEJM 2017; 377: 143-53) find that a better diet quality is associated with lower total and cause-specific mortality.

This study analyzed two large cohorts:

  • The Nurses’ Health Study -a prospective study with 121,700 RNs –enrollment initiated in 1976
  • The Health Professionals Follow-up Study with 51,529 health professionals enrollment initiated in 1986

Diet quality was evaluated with three scoring systems:

  • The Alternate Healthy Eating Index with 11 food components
  • The Alternate Mediterranean Diet Score with 9 food components
  • The Dietary Approaches to Stop Hypertension (DASH) with 8 food components

Key findings:

  • “A 20-percentile increase in diet-quality scores was associated with an 8 to 17% reduction in mortality”
  • “Worsening diet quality over 12 years was associated with an increase in mortality of 6 to 12%.”
  • “Taken together, our findings provide support for the recommendations of the 2015 Dietary Guidelines Advisory Committee that it is not necessary to conform to a single diet plan to achieve healthy eating patterns.”
  • “Common food groups in each score that contributed most to improvements were whole grains, vegetables, fruits, and fish or n-3 fatty acids.”

Like most nutrition studies, this one has limitations.  Strengths of this particular study include the prospective design, large sample sizes, repeated assessments of diet/lifestyle, multiple diet assessments, and high rates of followup.

My take: There is no doubt that diet quality is associated with improved longevity. Better diets are highly likely to be the reason why many people live longer.

Dupont Forrest, NC

Afraid to Eat -Could be “Avoidant Restrictive Food Intake Disorder”

A recent case report (JJ Thomas et al. NEJM 2017; 376: 2377-86) provides insight into something I’ve seen a lot but did not have a good label for previously: Avoidant Restrictive Food Intake Disorder (ARFID).

This report highlights an 11 year old who after a having a piece of meat briefly lodged into an orthodontic palate expander, stopped eating solid foods because she was “afraid I can’t chew it up enough to swallow it so I don’t choke.”  Even before this event, she had been a highly selective eater since infancy.  “Similar to many patients with ARFID, this patient had a long-term failure to gain weight appropriately and now had more acute weight loss.”  She did desired to gain weight and did not have any body distortion typical for anorexia nervosa.

This report provides a good list of etiologies which could trigger acute food refusal as well as conditions that could cause chronic poor weight gain.

  • For acute food refusal, etiologies included acute oromotor dysfunction, foreign body ingestion, gastrointestinal ulceration, anorexia nervosa/other psychiatric reasons (including globus hystericus).
  • For chronic failure to gain weight: chronic oromotor dysfunction (numerous neurologic causes), achalasia, inflammatory bowel disease, celiac disease, endocrine etiologies (eg. Addison’s, hyperthyroidism, type 1 diabetes mellitus), infections (eg. tuberculosis, HIV), insufficient food/abuse & neglect, stimulant use, cancers, and other chronic diseases (pulmonary, cardiac, or renal)

Definition of ARFID:

  • “The presence of avoidant or restrictive eating that results in persistent failure to meet nutritional needs; evidence of ARFID includes low weight or failure to have expected gains or growth, nutritional deficiencies, reliance on nutritional supplements or enteral feeding, psychosocial impairment, or a combination of these features. Restrictive eating may be motivated by low appetite or lack of interest in eating, sensitivities to certain sensory aspects of foods, or fear of adverse consequences of eating, such as choking or vomiting.”
  • It is noted that coexisting psychiatric conditions “appear to be common among patients with ARFID. Concurrent anxiety disorders are the most prevalent; they occur in more than 70% of patients in some clinical samples.”

Treatment of ARFID:

There is little data to guide treatment.  Treatment of coexisting psychiatric conditions is recommended and behavioral interventions to improve eating.  In this patient with a choking phobia, the treatment included a gradual stepwise progression in food textures:

  • Liquids–>Purees (eg yogurt, applesauce)–>Textured purees (eg. oatmeal, mashed potatoes) –>Soft solids (eg. rice, mac & cheese, pasta, bread, potatoes, pizza) –>Crunchy solids (eg. chips, pretzels, crackers) –>Hard-to-chew solids (eg. meats)

My take: I think being able to use this relatively new term of Avoidant Restrictive Food Intake Disorder will improve disease classification and ultimately help promote better treatments.

I thought this candy store icon was funny due to the missing tooth

8 Cups of Water: Weight Loss or Worthless?

A recent study: JMW Wong et al. JAMA Pediatr 2017; 17 e170012 (Thanks to Ben Gold for this reference)

Full Text Link: Effects of Advice to Drink 8 Cups of Water per Day in Adolesents with Overweight or Obesity: A Randomized Clinical Trial

Among 38 adolescents with overweight or obesity, participants were divided into a water group and a control group.  The water group received “well-defined messages about water through counseling and daily text messages, a water bottle, and a water pitcher with filters.”

Key findings:

  • The water group consumed 2.8 cups of water per day compared to 1.2 cups per day for the control group
  • The 6-month chnage in BMI z score was identical z= -0.1.

My take: Advice and behavioral supports to consume 8 cups of water per day are likely to fall short and do not seem to enhance weight loss.

Related blog posts:

Normandy American Cementary

Little Evidence to Support Dietary Intervention in Autism Spectrum Disorders

Thanks to Kipp Ellsworth Twitter feed for reference:  Nutritional and Dietary Interventions for Autism Spectrum Disorder: A Systematic Review N Sathe Pediatrics 2017; vol 139.


CONTEXT: Children with autism spectrum disorder (ASD) frequently use special diets or receive nutritional supplements to treat ASD symptoms.

OBJECTIVES: Our objective was to evaluate the effectiveness and safety of dietary interventions or nutritional supplements in ASD.

DATA SOURCES: Databases, including Medline and PsycINFO.

STUDY SELECTION: Two investigators independently screened studies against predetermined criteria.

DATA EXTRACTION: One investigator extracted data with review by a second investigator. Investigators independently assessed the risk of bias and strength of evidence (SOE) (ie, confidence in the estimate of effects).

RESULTS: Nineteen randomized controlled trials (RCTs), 4 with a low risk of bias, evaluated supplements or variations of the gluten/casein-free diet and other dietary approaches. Populations, interventions, and outcomes varied. Ω-3 supplementation did not affect challenging behaviors and was associated with minimal harms (low SOE). Two RCTs of different digestive enzymes reported mixed effects on symptom severity (insufficient SOE). Studies of other supplements (methyl B12, levocarnitine) reported some improvements in symptom severity (insufficient SOE). Studies evaluating gluten/casein-free diets reported some parent-rated improvements in communication and challenging behaviors; however, data were inadequate to make conclusions about the body of evidence (insufficient SOE). Studies of gluten- or casein-containing challenge foods reported no effects on behavior or gastrointestinal symptoms with challenge foods (insufficient SOE); 1 RCT reported no effects of camel’s milk on ASD severity (insufficient SOE). Harms were disparate.

LIMITATIONS: Studies were small and short-term, and there were few fully categorized populations or concomitant interventions.

CONCLUSIONS: There is little evidence to support the use of nutritional supplements or dietary therapies for children with ASD.

Related blog post: Gluten-free, Casein-free -No improvement in Autism

Bayeux, France