naturopathydigest.com -- Critical Research

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Critical Research

Critical Research is a regular feature in Naturopathy Digest. Each month, we provide abstracts from studies published in the top peer-reviewed journals; each abstract includes the complete citation and an online link to the journal. Whenever possible, this link directs you to a page where you can order the full text of the study, if desired.

This Month's Featured Abstract

High-dose zinc to terminate angina pectoris: a review and hypothesis for action by ICAM inhibition.

George A. Eby, William W. Halcomb

We reviewed the literature related to the effects of high-dose zinc in arteriosclerosis-induced angina pectoris. Lipid peroxidation and LDL oxidation are believed to be critical for arteriosclerosis, and consequently angina pectoris. Administration of biologically available zinc was a beneficial treatment in a significant percentage of patients with severely symptomatic, inoperable atherosclerotic disease. In these patients, there was no difference in zinc concentration between patients with and without atherosclerosis in whole blood, erythocytes or hair, but there was a major difference between normal aorta and diseased aortas (40.6 ppm zinc in normal aorta vs. 23.2 ppm zinc in atherosclerotic aorta, 40.6 ppm zinc in normal aorta vs. 19.4 ppm zinc in atherosclerotic aneurysm aorta, and no difference between normal and aneurysm aorta), although copper was low in aneurysm aorta. Medication with high-dose zinc sulfate to raise zinc serum concentrations from 95 to 177 lg/dl resulted in objective improvement in 12 of 16 of these patients, including a patient who also had Reynard's disease.
Long-term environmental exposure to zinc resulted in a 40% reduction in the incidence of angina of effort compared to people not exposed to environmental zinc (P < 0.01) and a 40% reduction in the incidence of probable ischemia in exercise (P < 0.001). Lead had no effect while cadmium exposure resulted in more than tripling the incidence of angina of effort (P < 0.001). The antioxidative action of zinc prevents oxidation of LDL cholesterol and consequently stops the main mechanism of atherogenesis. Zinc blocks calcium and its several actions on atherogenesis. Increased amounts of cytotoxic cytokines such as TNF-a, IL-b and IL-8, often produced in the elderly, are blocked by high-dose zinc.
We hypothesize that higher serum concentrations of LDL cholesterol resulting from administration of 300 mg of zinc per day is caused by a release of low-density cholesterol from cardiovascular tissues, beneficially flushing it into the serum where it is readily observed, thus decreasing arteriosclerosis, increasing circulation, terminating angina pectoris and restoring more youthful cardiac function. Although prevention of cholesterol-induced arteriosclerosis by zinc is predicted from findings related to oxidative stress and lipid peroxidation, removal of LDL might be attributable to action of ionic zinc on ICAM inhibition. In stark contrast to current practice, high-dose zinc should be considered as basic in the strategy of prophylaxis and therapy of the atherosclerosis process to terminate angina pectoris and restore youthful cardiac function.
Source: Medical Hypotheses 2006;66:169-72.

Magnesium deficiency in critical illness.

Garrison M. Tong, MD, and Robert K. Rude, MD, from the University of Southern California, School of Medicine.

Magnesium (Mg) deficiency commonly occurs in critical illness and correlates with a higher mortality and worse clinical outcome in the intensive care unit (ICU). Magnesium has been directly implicated in hypokalemia, hypocalcemia, tetany, and dysrhythmia. Moreover, Mg may play a role in acute coronary syndromes, acute cerebral ischemia, and asthma. Magnesium regulates hundreds of enzyme systems. By regulating enzymes controlling intracellular calcium, Mg affects smooth muscle vasoconstriction, important to the underlying pathophysiology of several critical illnesses. The principle causes of Mg deficiency are gastrointestinal and renal losses; however, the diagnosis is difficult to make because of the limitations of serum Mg levels, the most common assessment of Mg status. Magnesium tolerance testing and ionized Mg2+ are alternative laboratory assessments; however, each has its own difficulties in the ICU setting. The use of Mg therapy is supported by clinical trials in the treatment of symptomatic hypomagnesemia and preeclampsia, and is recommended for torsade de pointes. Magnesium therapy is not supported in the treatment of acute myocardial infarction and is presently undergoing evaluation for the treatment of severe asthma exacerbation, for the prevention of postcoronary bypass grafting dysrhythmias, and as a neuroprotective agent in acute cerebral ischemia.
Source: Journal of Intensive Care Medicine 2005;20(1):3-17.

Neutralization of Western diet inhibits bone resorption independently of K intake and reduces cortisol secretion in humans.

Marc Maurer, Walter Riesen, Juergen Muser, Henry N. Hulter, and Reto Krapf

A Western-type diet is associated with osteoporosis and calcium nephrolithiasis. On the basis of observations that calcium retention and inhibition of bone resorption result from alkali administration, it is assumed that the acid load inherent in this diet is responsible for increased bone resorption and calcium loss from bone. However, it is not known whether the dietary acid load acts directly or indirectly (i.e., via endocrine changes) on bone metabolism. It is also unclear whether alkali administration affects bone resorption/calcium balance directly or whether alkali-induced calcium retention is dependent on the cation (i.e., potassium) supplied with administered base. The effects of neutralization of dietary acid load (equimolar amounts of NaHCO₃ and KHCO₃ substituted for NaCl and KCl) in nine healthy subjects (six men, three women) under metabolic balance conditions on calcium balance, bone markers, and endocrine systems relevant to bone [glucocorticoid secretion, IGF-1, parathyroid hormone (PTH)/1,25(OH)₂ vitamin D and thyroid hormones] were studied.
Neutralization for seven days induced a significant cumulative calcium retention (10.7 0.4 mmol) and significantly reduced the urinary excretion of deoxypyridinoline, pyridinoline, and n-telopeptide. Mean daily plasma cortisol decreased from 264 45 to 232 43 nmol/l (P = 0.032), and urinary excretion of tetrahydrocortisol (THF) decreased from 2,410 210 to 2,098 190 µg/24 h (P = 0.027). No significant effect was found on free IGF-1, PTH/1,25(OH)₂ vitamin D, or thyroid hormones. An acidogenic Western diet results in mild metabolic acidosis in association with a state of cortisol excess, altered divalent ion metabolism, and increased bone resorptive indices. Acidosis-induced increases in cortisol secretion and plasma concentration may play a role in mild acidosis-induced alterations in bone metabolism and possibly in osteoporosis associated with an acidogenic Western diet.
Source: Am J Physiol Renal Physiol 2003;284:F32-F40.

Association of H2-blocker therapy and higher incidence of necrotizing enterocolitis in very low birth weight infants.

Ronnie Guillet, MD, PhD; Barbara J. Stoll, MD; C. Michael Cotten, MD; Marie Gantz, PhD; Scott McDonald, BS; W. Kenneth Poole, PhD; and Dale L. Phelps, MD

Objective: We sought to determine if an association exists between the use of histamine-2 receptor (H2) blockers and the incidence of necrotizing enterocolitis (NEC) in infants of 401g to 1500 g in birth weight.
Study design: Data from the National Institute of Child Health and Human Development Neonatal Research Network very low birth weight (401-1500 g) registry from September 1998 to December 2001 were analyzed. The relation between the diagnosis of NEC (Bell stage II or greater) and antecedent H2-blocker treatment was determined by using case-control methodology. Conditional logistic regression was implemented, controlling for gender, site of birth (outborn versus inborn), Apgar score of <7 at 5 minutes, and postnatal steroids.
Results: Of 11,072 infants who survived for at least 12 hours, 787 (7.1%) developed NEC (11.5% of infants 401-750 g, 9.1% of infants 751-1,000 g, 6.0% of infants 1,001-1,250 g, and 3.9% of infants 1,251-1,500 g). Antecedent H2-blocker use was associated with an increased incidence of NEC (P < .0001).
Conclusions: H2-blocker therapy was associated with higher rates of NEC, which is in agreement with a previous randomized trial of acidification of infant feeds that resulted in a decreased incidence of NEC. In combination, these data support the hypothesis that gastric pH level may be a factor in the pathogenesis of NEC.
Source: Pediatrics, February 2006;117(2):e137-e142..

Low dietary potassium intakes and high dietary estimates of net endogenous acid production are associated with low bone mineral density in premenopausal women and increased markers of bone resorption in postmenopausal women.

Helen M. Macdonald, Susan A. New, William D. Fraser, Marion K. Campbell and David M Reid

Background: The Western diet may be a risk factor for osteoporosis. Excess acid generated from high protein intakes increases calcium excretion and bone resorption. Fruit and vegetable intake could balance this excess acidity by providing alkaline salts of potassium. Algorithms based on dietary intakes of key nutrients can be used to approximate net endogenous acid production (NEAP) and to explore the association between dietary acidity and bone health.
Objective: We investigated the relation between dietary potassium and protein, NEAP (with an algorithm including the ratio of protein to potassium intake), and potential renal acid load (with an algorithm including dietary protein, phosphorous, potassium, magnesium, and calcium) and markers of bone health.
Design: Measurements of bone mineral density (BMD) (n = 3,226) and urinary bone resorption markers (n = 2,929) at the lumbar spine and femoral neck were performed in perimenopausal and early postmenopausal women ages 54.9 2.2 y ( SD) in 1997-1999. BMD (g/cm²), free pyridinoline (fPYD), and free deoxypyridinoline (fDPD) were expressed relative to creatinine. Dietary intake was assessed with a food-frequency questionnaire.
Results: Comparison of the highest with the lowest quartile of potassium intake or the lowest with the highest NEAP showed a 6% to 8% increase in fPYD/creatinine and fDPD/creatinine. A difference of 8% in BMD was observed between the highest and lowest quartiles of potassium intake in the premenopausal group (n = 337).
Conclusions: Dietary potassium, an indicator of NEAP and fruit and vegetable intake, may exert a modest influence on markers of bone health, which over a lifetime may contribute to a decreased risk of osteoporosis.
Source: American Journal of Clinical Nutrition, April 2005;81(4):923-33.

Dried fruits: excellent in vitro and in vivo antioxidants.

Joe A. Vinson, PhD, Ligia Zubik, PhD, Pratima Bose, PhD, Najwa Samman, MS, and John Proch, BS. Chemistry Department, University of Scranton, Scranton, Pa.

Objective: The goal of this work is to determine the amount and quality of phenol antioxidants in dried fruits and compare them with the corresponding fresh fruits; to compare the nutrients in fresh and dried fruits; and to determine if figs are a source of in vivo antioxidants when eaten.
Methods: Commercial samples of dried fruits and fresh fruits were compared in the in vitro studies using a colorimetric method to measure phenolic antioxidants. The quality of the antioxidants was measured by inhibition of lower density lipoprotein oxidation. Ten normal free-living subjects were tested in the human study. Fasting subjects were given 40 g of figs with or without a carbonated beverage and the plasma antioxidant capacity was measured for six hours using the trolox equivalent antioxidant capacity assay.
Results: Dates have the highest concentration of polyphenols among the dried fruits. Figs and dried plums have the best nutrient score among the dried fruits, and dates among the fresh fruits. Processing to produce the dried fruit significantly decreases the phenols in the fruits on a dry weight basis. Compared with vitamins C and E, dried fruits have superior quality antioxidants with figs and dried plums being the best. Fig antioxidants can enrich lipoproteins in plasma and protect them from subsequent oxidation. Figs produced a significant increase in plasma antioxidant capacity for four hours after consumption, and overcame the oxidative stress of consuming high-fructose corn syrup in a carbonated soft drink.
Conclusion: Dried fruits and especially figs are a convenient and superior source of some nutrients, but in the American diet they amount to less than 1% of total fruit consumed. Figs are in vivo antioxidants after human consumption. The findings suggest that dried fruits should be a greater part of the diet, as they are dense in phenol antioxidants and nutrients, most notably fiber.
Source: J Am Col Nutrition 2005;24(1):44-50.