Gut inflammation and stool tests overview

The gut’s immune system is ultimately responsible for maintaining a healthy gut free of infection or infestation. It must accomplish this task while at the same time being unresponsive to food and helpful bacteria (1).

Gastrointestinal inflammation etiology is largely infection such as via parasite. However, modern lifestyles have increasingly been harassed by new chronic inflammatory diseases such as Crohn’s or ulcerative colitis (1). These are associated mainly with genetic mutations or adaptive immunity affecting immune system recognition as well as by epithelial permeability (1).

Stool tests indicating gastrointestinal inflammation include those for fecal proteins such as eosinophil protein-X (EPX), fecal calprotectin (FC) and fecal myeloperoxidase (MPO):

• FC is a calcium-binding protein found in large amounts in neutrophils and macrophages, which rush into the lumen at onset of inflammation (2-4). FC is considered more sensitive than endoscopy, for example, for evaluating inflammatory bowel disease such as ulcerative colitis and Crohn’s disease. Calprotectin can also be used to determine post-infectious irritable bowel syndrome, NSAID enteropathy or cancer.
  
• MPO is a derivative of neutrophil granulocytes (2). It’s useful diagnostically because it’s found in intestinal mucosa and in feces. Levels of MPO are elevated in active inflammatory bowel disease and mark mucosal inflammation. MPO and FC appear to be better markers in comparison to EPX during the treatment of inflammatory diseases ulcerative colitis or Crohn’s disease (2).
  
• EPX is a glycoprotein that is released when eosinophil granulocytes (white blood cells responsible for battling infectious parasites and bacteria) (2). Its increased levels in feces reflect infection, inflammation and tissue damage relating to food allergies, celiac disease, helminthic infection, inflammatory bowel disease, and cancer (5).

Reference List

1. MacDonald TT, Monteleone G. Immunity, inflammation, and allergy in the gut. Science 2005;307:1920-5.
2. Wagner M, Peterson CG, Ridefelt P, Sangfelt P, Carlson M. Fecal markers of inflammation used as surrogate markers for treatment outcome in relapsing inflammatory bowel disease. World J Gastroenterol 2008;14:5584-9.
3. Savino F, Castagno E, Calabrese R, Viola S, Oggero R, Miniero R. High Faecal Calprotectin Levels in Healthy, Exclusively Breast-Fed Infants. Neonatology 2009;97:299-304.
4. Gaya DR, Mackenzie JF. Faecal calprotectin: a bright future for assessing disease activity in Crohn's disease. QJM 2002;95:557-8.
5. Genova Diagnostics. 2009. "Comprehensive Digestive Stool Analysis 2.0" Gastrointestinal Assessments. Available at: http://blackboard.bridgeport.edu/@@651E45893EFF586CEA74E9CF68D701AA/courses/1/NUTR-560E-DLB-2009NF/content/_22116_1/Comprehensive%20Digestive%20Stool%20Analysis-%20Genova.pdf. Accessed 28 Nov 2009.

Kid Nutrition

Nutritional and energy needs for a child differs profoundly from that of an adult because of a child's continual growth and development. A child is in greater need of nutrient-dense foods--although not to the extent as infants--and requires more energy for basal metabolic rate, physical activity and thermic effect of food. Energy needs are highest during rapid growth and expansion of lean mass.

Each individual child is best understood by first dividing stages of child growth and development into two periods: a preschool period and a school-age period:

• During the pre-school period, from 2-6 years of age, the child grows more slowly in comparison to infancy. A toddler will quadruple birth weight in a full year or so. The brain of the toddler also grows more slowly than as was expected as an infant so head circumference will only increase by a couple of centimeters. A toddler's weight increase can range from 2.5 kg per year for ages 2 and 3 to 2 kg per year for ages 4 and 5. She or he will also grow about 12 cm from age 2 and 3. During that time, body composition will also change as total body water content settles to a comfortable 60-65% and growth of new cells and skeletal muscle causing a decrease in extracellular fluid and increase in intracellular fluid.
  
• The school-age period, or latent growth period, beigns from 6 until puberty of which girls can reach a little earlier at 10 and boys normally at 12. As "baby fat" is lost, the child becomes leaner and mor muscular. The pattern of growth is highly individual. On average, weight increase will be about 3-3.5 kg per year during this period. The child will move beyond the limited vocabulary of three-word-sentences and begin adapting to an environnment of greater language skills, motor skills, as well as personal-social skills. This, of course, will also mean more control over diet through self-feeding.

As both periods represent critical times for growth and development, the focus of recommendations for energy and nutrient intake are based on supporting optimal outcomes. The recommendations are, again, more critical than for adults because of dire long-term consequences. A child, for example, will need special attention to be sure that they receive proteins of high biologic value for growth requirements. Fat and carbohydrate needs will be greater during rapid growth periods as will numerous vitamins and minerals, especially vitamin D and calcium of which are largely deficient in children. Fiber too, which helps normalize bowel movements, is critical for ensuring a child lives free of future risk of disease. All in all the goal is to provide the best support to provide children with bright futures.

Summarized from

Mitchell MK. Nutrition Across the Life Span. "Chapter 9: Nutrition During Growth: Preschool through Preadolescence". Second Edition. Waveland Press: Long Grove, Illinois, 2003, pp. 271-300.

Somatic Protein Status

Protein status is assessed by evaluating both somatic and visceral protein status. Somatic protein status is a measure of the protein in skeletal muscle while visceral protein status is a measure of all other proteins (organs, viscera, serum, blood cells, white blood cells).

Evaluation of somatic protein status can generally be performed using muscle circumference or mid-arm muscle area. However, because no single indicator is completely accurate biochemical measures can help better provide perspective for somatic protein status.

Creatinine serves as a useful measure because creatinine is produced in the skeletal muscle. The more skeletal muscle a person has, the more creatinine will be excreted. A 24-hour urinary creatinine excretion test is easily tested in the laboratory. The measure can then be compared to standards based on stature and body weight. The 24-hour urinary creatinine excretion can also be compared to reference values from the creatinine-height index (CHI). The CHI is a ratio of 24-hour urinary creatinine excretion and an expected amount depending on sex and stature. Creatinine measures have their limits samples have to be collected in exactly 24 hours and diet can compromise creatinine measurements and, thus, measures of excretion and CHI.

The amino acid, 3-methylhistidine, is another useful measure of muscle mass because it is found in the contractile proteins of muscle, actin and myosin. It is releasaed when the contractile proteins are catabolized and excreted in the urine. As long as protein synthesis and degradation is steady, the amount of 3-methylhistidine should paint a picture of muscle mass. However, just as 24-hour urinary creatinine excretion, the measure of 3-methylhistine is limited. The value can be affected by diet, age, sex, maturity, hormonal status, physical shape, any recent intense exercise, injury or disease. A significant pool of 3-mehtylhistidine also lies outside of skeletal muscle that also creates complication as an index of skeletal protein breakdown.

Energy needs of healthy term and high-risk infant

The infant, despite whether healthy term or high-risk, will require energy for BMR, thermic effect of food, physical activity, maintenance, growth and for energy lost in feces and urine. There is also energy needed just to maintain body temperature until the early extrauterine period passes. The newborn requires approximately 108 kcal/kg for about six months followed by 98 kcal/kg for the next six.

The high-risk newborn will have the same energy requirements, but Calorie needs will differ in whether or not the infant is enterally fed or parenterally fed. The enterally fed infant needs a greater amount of Calories, at 120/kg, than the healthy infant due to specific dynamic action and cold stress. The parentally fed will need fewer amount of Calories, at about 80-90 kcal/kg, than the healthy infant because of the infant won't use as many calories for activity, cold stress, specific dynamic action or stool losses. Caloric needs for both enterally and parenterally fed high-risk infants will aslo need to depend on medical problems and growth needs.

Assessment methods by which energy needs are determined include anthropometry, biochemical assessment and dietary assessment. Anthropometry assesses weight, length and head circumference. Because weight is most important for the high-risk infant, it will need to be weighed one or more times daily. Biochemcial lab measurements will need to be performed over several days in the high-risk infant to determine development.

The high-risk infant will also need a clinical assessment and a nutrient intake assessment. The clincal assessment will evaluate condition including state of hydration relative to urine and weight gain as well as feeding tolerance including vomiting records. Nutrient intake will evaluate nutrient sources in a qualitative fashion as well as nutrients in terms of quantity. Nutrient sources will need to depend on the condition of the high-risk infant such as state of digestive abilities. Nutrient amounts depends on absorption capacities, whether parenterally or enterally fed and weight.

Reference

Mitchell MK. Nutrition Across the Life Span. Second Edition. Waveland Press: Long Grove, Illinois, 2003.

Protein-deficient diet and teratogenicity

One interesting detail I came across while researching teratogens is that a protein-deficient diet may enhance the effects of xenobiotics in general.

For example, dietary protein deficiency along with exposure to inorganic arsenic through injection in mice was found to increase risk of birth defects, possibly because of lack of methyl donors for arsenic methylation (1). Also, high-dose caffeine teratogenicity is increased when in combination with protein deficiency (2).

Other xenobiotics such as tobacco carcinogens, anticonvulsants and sedatives appear to be teratogenic depending on the status of the cytochrome P450 system of the fetus (1). The effect may or may not be related to protein deficiency. The toxicity is thought to occur due to lack of anitoxidative enzymes such as GSH peroxidase and GSH reductase, which would increased endogenous oxidative stress and cumulative damage (3).

Reference List

1. Lammon CA, Hood RD. Effects of protein deficient diets on the developmental toxicity of inorganic arsenic in mice. Birth Defects Res B Dev Reprod Toxicol 2004;71:124-34.
2. Nehlig A, Debry G. Potential teratogenic and neurodevelopmental consequences of coffee and caffeine exposure: a review on human and animal data. Neurotoxicol Teratol 1994;16:531-43.
3. Wells PG, Kim PM, Laposa RR, Nicol CJ, Parman T, Winn LM. Oxidative damage in chemical teratogenesis. Mutat Res 1997;396:65-78.

Caffeine and pregnancy

I was shocked to learn that FDA in 1980 had determined that caffeine in amounts exceeding 300 mg could potentially be teratogenic (1). Teratogens are agents that cause fetal malformations or birth defects. Good thing caffeine does not harm the fetus when taken in smaller amounts, despite evidence in rats to the contrary (1-2).

However, after digging deeper, I found that the researchers did find that caffeine potentiated teratogenic effect of smoking and alcohol (2). The mechanism appears to be through inducing materno-fetal vasoconstrictions that lead to ischemia (2).

If caffeine potentiates effects of other teratogens in amounts less than 300 mg, I imagine it's still wise of pregnant women to avoid caffeine altogether during pregnancy just in case they are exposed to teratogens of some kind and are unaware of it.

Reference List

1. Mitchell MK. Nutrition Across The Life Span. Long Grove, IL: Waveland Press, 2003.
2. Nehlig A, Debry G. Potential teratogenic and neurodevelopmental consequences of coffee and caffeine exposure: a review on human and animal data. Neurotoxicol Teratol 1994;16:531-43.

Cannabis Teratogenicity

Cannabis sativa’s psychoactive tetrahydrocannabinol (THC) has not been established as a human teratogen (1), but there is a history of teratogenic effects linked to use by expectant mothers (2). The perinatal exposure is thought to interfere with neurodevelopment and affect neurobehavorial outcomes (1-2).

Although the teratogenicity of marijuana is not as catastrophic as other illicit drugs such as cocaine, it’s harm can still lead to problems such as disturbed sleep and attention deficit disorder (2-3). Worth noting is that when cocaine exposure is accompanied by marijuana, the neurological effects can be pronounced (3).

There is also indication that maternal marijuana use may increase risk of acute myeloid leukemia, however, more recent research has not been able to confirm this relationship (4).

Reference List

1. Kozer E, Koren G. Effects of prenatal exposure to marijuana. Can Fam Physician 2001;47:263-4.
2. Reece AS. Chronic toxicology of cannabis. Clin Toxicol (Phila) 2009;47:517-24.
3. Frank DA, Augustyn M, Knight WG, Pell T, Zuckerman B. Growth, development, and behavior in early childhood following prenatal cocaine exposure: a systematic review. JAMA 2001;285:1613-25.
4. Trivers KF, Mertens AC, Ross JA, Steinbuch M, Olshan AF, Robison LL. Parental marijuana use and risk of childhood acute myeloid leukaemia: a report from the Children's Cancer Group (United States and Canada). Paediatr Perinat Epidemiol 2006;20:110-8.

When you’re eating for twins or more

Nutritional needs soar when you have a multiple pregnancy. According to Barbara Luke from University of Miami, the mother has a “greater nutritional drain” on her body. Because of quicker glycogen depletion that might slow fetal growth rate, Luke suggests a diabetic regimen with caloric ratio of 40% carbs, 20% protein, and 40% fat. In addition, she suggests supplementation with iron, calcium, magnesium and selenium for preventing “complications and improvement of postnatal health”.

Reference List

Luke B. Nutrition and multiple gestation. Semin Perinatol 2005;29:349-54.

Eggs for Pregnancy

Eggs, considered a nutritional powerhouse, is an excellent food to recommend to these women during pregnancy. According to Niva Shapira of Tel-Aviv University in Israel, eggs can provide various nutrients, vitamins and minerals that are also found in human milk and that support peak brain development (1).

If those eggs are also produced in such a way as to contain high levels of DHA, then they become even more supportive to the young one’s brain (2).

Reference List

1. Shapira N. Modified egg as a nutritional supplement during peak brain development: a new target for fortification. Nutr Health 2009;20:107-18.

2. Carlson SE. Docosahexaenoic acid supplementation in pregnancy and lactation. Am J Clin Nutr 2009;89:678S-84S.

Low-fat vs low-carb and Med-diet

On July 17, 2008, a study was published (1) that I believe should change how nutritionists and dietitians would look at the current Dietary Guide for Americans, the Food Guide Pyramid and the whole concept of a “heart-healthy” low-fat diet as recommended by the American Heart Association.

The paradigm-shift study was a 2-year intervention trial in The New England Journal of Medicine in which weight loss was compared among moderately obese subjects who were assigned to either a restricted-calorie Mediterranean diet, a non-restricted calorie low-carbohydrate, or a typical restricted-calorie low-fat diet (1). What did they find? Surprising results.

All the subjects lost weight, but were greater in both the low-carbohydrate group (despite nonrestricted calories) and the Mediterranean-diet group (1). The lipid profiles, more surprisingly, improved in the Mediterranean-diet group and most in the low-carbohydrate group (1). Best LDL cholesterol levels were found among the Mediterranean-diet group (1). The level of high-sensitivity C-reactive protein, most surprisingly, improved only in the Mediterranean-diet and low-carbohydrate groups (1).

The study, going further, took into consideration those with diabetes by measuring their fasting plasma glucose, insulin and glycated hemoglobin levels. There were no significant changes in fasting plasma glucose levels, but drastic decreasaes in insulin levels across the board (1). But the glycated hemoglobin decreased the most in the low-carb group (1).

Given the results of this study, my inclination is to adopt the Harvard School of Public Health’s Healthy Eating Pyramid because it appears to more resemble the Mediterranean-style of eating. And I would add recommendation for lower-carb eating in general along with inclusion of monounsaturated fat from olive oil and higher intake of fish versus red meat, etc.

Reference List

1. Cheskin LJ, Kahan S. Low-carbohydrate and Mediterranean diets led to greater weight loss than a low-fat diet in moderately obese adults. Evid Based Med 2008;13:176.