Literature review and comment

By Alan R. Gaby, M.D.

Contents:

1. Do saunas prevent dementia?

2. Acupuncture vs. morphine for acute pain

3. Inositol prevents gestational diabetes

4. Another fetus damaged by high-dose maternal iodine supplementation

5. Potassium interaction with medications

6. High-dose intravenous magnesium for severe asthma

7. Adverse effect of a probiotic

8. Dilute apple juice to treat gastroenteritis

Do Saunas Prevent Dementia?

The association between frequency of sauna bathing and incidence of dementia and Alzheimer’s disease was examined in a prospective cohort study of 2,315 apparently healthy Finnish men (aged 40-60 years) participating in the Kuopio Ischaemic Heart Disease study. Twelve men who did not use saunas were excluded from the study. During a median follow-up period of 20.7 years, a total of 204 cases of dementia and 123 cases of Alzheimer’s disease were diagnosed. After adjustment for potential confounding variables including age, alcohol consumption, body mass index, systolic blood pressure, smoking status, type 2 diabetes, and previous myocardial infarction, compared with men engaging in one sauna bathing session per week, the hazard ratio for dementia was 0.78 (95% confidence interval [CI], 0.57-1.06) for two to three sessions per week and 0.34 (95% CI, 0.16-0.71) for four to seven sessions per week. The corresponding hazard ratios for Alzheimer’s disease were 0.80 (95% CI, 0.53-1.20) and 0.35 (95% CI, 0.14-0.90).

Comment: Sauna bathing has long been a tradition in Finland. A traditional Finnish sauna has dry air with a relatively high temperature (average, 176° F). In the present study, more frequent sauna bathing was associated with a lower risk of developing dementia and Alzheimer’s disease. If this association is causal, possible mechanisms include improved cardiovascular and circulatory function and the removal of potentially neurotoxic xenobiotic chemicals through sweating.

Laukkanen T, et al. Sauna bathing is inversely associated with dementia and Alzheimer’s disease in middle-aged Finnish men. Age Ageing. 2016 Dec 7 [Epub ahead of print].

Acupuncture vs. Morphine for Acute Pain

Three hundred patients presenting to an emergency department with acute pain were randomly assigned to treatment with acupuncture or morphine. Common causes of pain included acute musculoskeletal pain with no evidence of fracture or dislocation; ankle and knee sprains; shoulder and elbow tendonitis; low back pain with no evidence of neurological deficit; acute abdominal pain with no need for urgent surgical intervention; dysmenorrhea; and acute headache. Acupuncture was administered by a trained acupuncturist, using standardized protocols that allowed for enough discretion to individualize the treatment. Morphine was administered intravenously at an initial dose of 0.1 mg per kg of body weight, and then repeated at half that dose every five minutes until pain relief was achieved or until a total dose of 15 mg had been given. The proportion of patients who experienced at least a 50% reduction in pain during the first 60 minutes was significantly higher in the acupuncture group than in the morphine group (92% vs. 78%; p < 0.001). Mean time until resolution of pain was significantly shorter in the acupuncture group than in the morphine group (16 vs. 28 minutes; p < 0.005). Minor adverse effects were experienced by 2.6% of patients receiving acupuncture and 56.6% of those receiving morphine (p < 0.001).

Comment: This study demonstrated that acupuncture was more effective and better tolerated than intravenous morphine in the treatment of acute pain due to various causes. Considering the major problem with opioid addiction in the United States, acupuncture should be considered as an alternative to morphine for selected patients presenting to emergency departments with acute pain.

Grissa MH, et al. Acupuncture vs intravenous morphine in the management of acute pain in the ED. Am J Emerg Med. 2016;34:2112-2116.

Inositol Prevents Gestational Diabetes

Two hundred twenty overweight, non-obese pregnant women without gestational diabetes were randomly assigned to receive, in single-blind fashion, 2 g of myo-inositol plus 200 µg of folic acid or placebo (200 µg of folic acid) twice a day from week 12-13 of gestation until delivery. The incidence of gestational diabetes was significantly lower by 58% in the myo-inositol group than in the placebo group (11.6% vs. 27.4%; p = 0.004).

Comment: myo-Inositol (commonly called inositol) is a vitamin-like compound present in some foods, which is also synthesized in the body from glucose. It is a constituent of certain phospholipids that are components of biological membranes and lipoproteins. It is also an intermediate of the phosphatidylinositol cycle, a second-messenger neuronal signaling system used by noradrenergic, serotonergic, and cholinergic receptors. The results of the present study indicate that supplementation with myo-inositol can decrease the incidence of gestational diabetes in overweight pregnant women.

While myo-inositol’s mechanism of action is not clear, it might work in part by being converted to D-chiro-inositol, which is a stereoisomer of myo-inositol. D-chiro-Inositol is a component of an endogenous phosphoglycan that is involved in a post-receptor insulin-mediated signaling pathway. As such, D-chiro-inositol presumably plays a role in enhancing insulin sensitivity.

Santamaria A, et al. Myo-inositol may prevent gestational diabetes onset in overweight women: a randomized, controlled trial. J Matern Fetal Neonatal Med. 2016;29:3234-3237.

Another Fetus Damaged by High-Dose Maternal Iodine Supplementation

A 27-year-old woman had been taking 12.5 mg per day of iodine/iodine in addition to desiccated thyroid during pregnancy, to treat hypothyroidism. The excessive iodine consumption caused suppression of fetal thyroid hormone production, resulting in fetal hypothyroidism and goiter. After the iodine supplement was discontinued, the fetal goiter decreased in size. Postnatally, the infant had reversible hypothyroidism and irreversible bilateral hearing loss. Deafness is a known result of untreated hypothyroidism, but it is not clear whether the hearing loss in this case was caused by hypothyroidism.

Comment: Over the past few years, there have been a number of case reports of neonatal hypothyroidism in the infants of mothers who took large amounts of iodine during pregnancy. In the present case report, high-dose iodine was being used to treat hypothyroidism. While iodine deficiency can cause hypothyroidism, and while supplementation with small amounts of iodine can reverse hypothyroidism that is due to iodine deficiency, there is no justification for using high-dose iodine to treat hypothyroidism. If anything, high-dose iodine makes hypothyroidism worse (Kasagi K, et al. Effect of iodine restriction on thyroid function in patients with primary hypothyroidism. Thyroid. 2003;13:561-567). The Recommended Dietary Allowance (RDA) for iodine during pregnancy is 220 µg per day. While iodine supplementation (typically as a component of a prenatal multivitamin formula) is often needed to achieve the RDA during pregnancy, iodine doses substantially larger than the RDA should be avoided during pregnancy.

Overcash RT, et al. Maternal iodine exposure: a case of fetal goiter and neonatal hearing loss. Pediatrics. 2016;137:e20153722.

Potassium Interaction with Medications

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) decrease urinary potassium excretion, which may increase the risk of hyperkalemia in people who are consuming a high-potassium diet or taking potassium supplements. In the present study, 20 hypertensive subjects with normal renal function who were being treated with an ACE inhibitor or ARB were randomly assigned to consume a usual diet or a high-potassium diet, which was achieved by increasing intake of fruits and vegetables. After four weeks, compared with baseline, the high-potassium group had significant increases in dietary potassium (5,212 vs. 3,775 mg per day; p = 0.02) and urinary potassium excretion (4,260 vs. 3,244 mg per day). In contrast, the mean serum potassium concentration increased only nonsignificantly, from 4.1 mmol/L to 4.2 mmol/L.

Comment: High potassium intake is beneficial for hypertensive individuals because it decreases blood pressure. In addition, most high-potassium foods also contain other cardioprotective nutrients. However, in patients taking ACE inhibitors or ARBs for hypertension, increasing potassium intake must be approached with caution because of the potential for these drugs to cause hyperkalemia. In the present study, increasing dietary potassium intake for four weeks did not adversely affect serum potassium levels in hypertensive patients with normal renal function who were being treated with an ACE inhibitor or ARB. Additional research is needed to determine whether high potassium intake for more than four weeks is safe for patients taking these medications. In addition, the findings from this study may not apply to patients with impaired renal function.

Malta D, et al. Adequate intake of potassium does not cause hyperkalemia in hypertensive individuals taking medications that antagonize the renin angiotensin aldosterone system. Am J Clin Nutr. 2016;104:990-994.

High-Dose Intravenous Magnesium for Severe Asthma

Thirty-eight children (aged 6-16 years) with a severe asthma attack that was not associated with an infection and that had failed to improve after two hours of standard therapy were randomly assigned to receive, in open-label fashion, a bolus of magnesium sulfate (50 mg per kg of body weight over 1 hour) or a high-dose prolonged magnesium sulfate infusion of (50 mg per kg per hour for 4 hours; maximum, 8 g over 4 hours). Patients were monitored for cardiorespiratory complications. The proportion of children who were discharged from the hospital at 24 hours was significantly higher in the prolonged-treatment group than in the bolus group (47% vs. 10%; p = 0.032). The number need to treat was 2.7, which means that one hospitalization was prevented for every 2.7 children treated. Among the children who were hospitalized, mean length of hospital stay was significantly shorter (34.1 vs. 48.1 hours; p = 0.013) and mean cost per patient was one-third lower (p < 0.016) in the prolonged-treatment group than in the bolus group. No patient required discontinuation of treatment because of adverse events, and there were no reports of hypotension.

Comment: Several studies have found that intravenous administration of magnesium sulfate can improve symptoms and decrease the need for hospitalization in children with acute asthma attacks. In most of these studies, the dosage was 25-50 mg per kg (maximum dose, 2 g), administered over a period of 20 minutes. In the present study, a four-hour continuous magnesium infusion with a higher total dose was more effective than the dosage used in previous clinical trials. While high-dose magnesium was well tolerated in this study, it can cause hypotension, bradycardia, and other potentially serious side effects. High-dose intravenous magnesium should therefore be given with caution, and the patients should be monitored closely.

Irazuzta JE, et al. High-dose magnesium sulfate infusion for severe asthma in the emergency department: efficacy study. Pediatr Crit Care Med. 2016;17:e29-e33.

Adverse Effect of a Probiotic

A 78-year-old man with severe bicuspid aortic valve stenosis complicated by diffuse left ventricular mid-layer fibrosis, who had been consuming probiotics regularly, developed Lactobacillus paracasei endocarditis. He had had a tooth extraction six months previously.

Comment: While probiotics are generally considered safe, they have on rare occasions caused severe infections (septicemia: bacteremia from Lactobacillus strains or fungemia from Saccharomyces strains). Known predisposing factors to probiotic-induced septicemia include compromised immune function, a damaged gastrointestinal barrier, the presence of an indwelling central venous catheter, severe underlying disease, prior surgical interventions, prior prolonged hospitalization, administration of multiple antibiotics, and prolonged treatment with probiotics or use of excessive dosages. The present case report suggests that probiotics should not be given before dental procedures to patients with valvular heart disease.

Kato K, et al. Lactobacillus paracasei endocarditis in a consumer of probiotics with advanced and severe bicuspid aortic valve stenosis complicated with diffuse left ventricular mid-layer fibrosis. Int J Cardiol. 2016;224:157-161.

Dilute Apple Juice to Treat Gastroenteritis

Six hundred forty-seven children (aged 6-60 months; mean age, 28 months) in Toronto, Canada, presenting to an emergency department with gastroenteritis and minimal dehydration were randomly assigned to receive, in single-blind fashion, 1) rehydration with an electrolyte replacement solution or 2) half-strength apple juice followed by the child’s preferred fluids. After discharge, the apple juice/preferred fluids group was given fluids as desired, whereas the electrolyte replacement group continued to receive the electrolyte replacement solution as needed. The primary outcome measure was treatment failure, defined by any of the following occurring within seven days of enrollment: intravenous rehydration, hospitalization, unscheduled physician encounter, protracted symptoms, physician request to cross over to the other treatment, and 3% or more weight loss or significant dehydration at follow-up. The frequency of treatment failure was significantly lower with apple juice/preferred fluids than with electrolyte solution (17% vs. 25%; p = 0.006). ). In addition, fewer children administered apple juice/preferred fluids received intravenous rehydration (2.5% vs. 9.0%; p < 0.001).

Comment: In this study of children with mild gastroenteritis and minimal dehydration, initial oral hydration with dilute apple juice followed by their preferred fluids, as compared with an electrolyte replacement solution, resulted in fewer treatment failures. This treatment approach should therefore be considered as an alternative to commercially available electrolyte replacement solution in children with gastroenteritis.

Freedman SB, et al. Effect of dilute apple juice and preferred fluids vs electrolyte maintenance solution on treatment failure among children with mild gastroenteritis: a randomized clinical trial. JAMA. 2016;315:1966-1974.