One hundred forty-nine patients with longstanding recurrent idiopathic calcium oxalate and mixed calcium oxalate/calcium phosphate renal stones received 100 mg of magnesium oxide 3 times a day and 10 mg of pyridoxine once a day for 4.5 to 6 years. The mean rate of stone formation fell by 92.3%, from 1.3 stones per patient per year prior to the study to 0.10 stones per patient per year during the study. No significant side effects occurred.

Comment: Although there was no control group in this study, the results strongly suggest that supplementing with modest doses of magnesium and vitamin B6 can greatly reduce the recurrence rate of calcium oxalate kidney stones. The 300 mg/day of magnesium oxide used in this study is equivalent to 180 mg/day of elemental magnesium. Another uncontrolled study demonstrated that supplementing with 500 mg/day of magnesium (without vitamin B6) also reduced stone formation by about 90% (J Am Coll Nutr 1982;1:179-85).

Unfortunately, many doctors remain unaware of this simple, safe, effective, and inexpensive treatment for recurrent kidney stones. About 20 years ago, I was invited to speak on nutritional medicine at the annual meeting of the Baltimore County Medical Society. Because my presentation was expected to be controversial, the conference planner invited an "expert" in nutrition from a well-respected medical institution to provide comments after my talk. The "expert" refused the invitation, citing concerns that his appearance on the podium with me might give me a credibility that I did not deserve. He was particularly irked by an article I had written in Prevention magazine about how vitamin B6 and magnesium can help prevent kidney stones. After I sent the conference planner copies of the published research on vitamin B6, magnesium, and kidney stones, the "expert" apologized to the conference planner for his hostile reaction to my invitation. He still refused, however, to appear on the stage with me.

Prien EL Sr, Gershoff SN. Magnesium oxide-pyridoxine therapy for recurrent calcium oxalate calculi. J Urol 1974;112:509-512.

Ninety-seven patients (mean age, 48 years) with chronic renal failure (serum creatinine > 5 mg/dl), with a history of declining renal function for at least 12 weeks, were randomly assigned to receive, in double-blind fashion, water-soluble coenzyme Q10 (CoQ10; 60 mg, 3 times per day orally) or placebo for 12 weeks. The 45 patients who were receiving hemodialysis at the start of the study were encouraged to decrease the frequency or stop dialysis if there was an increase in urine output and a decrease in serum creatinine of more than 2 mg/dl. In the patients receiving hemodialysis and CoQ10, the mean serum creatinine concentration decreased from 9.5 to 6.7 mg/dl; mean BUN decreased from 88.2 to 79.8 mg/dl; mean creatinine clearance increased from 40 to 54.9 ml/min; and 24-hour urine output increased from 1,300 to 1,920 ml. Renal function tended to worsen in hemodialysis patients receiving placebo, and the differences in the changes between groups were significant (p < 0.01 to p < 0.001). Significant improvements in each of these parameters relative to the placebo group were also seen in the non-dialysis patients treated with CoQ10. The number of patients receiving dialysis decreased from 21 to 12 in the CoQ10 group, and remained unchanged at 24 in the placebo group (p < 0.02). Eighty-onepercent of the patients receiving CoQ10 had a positive response to treatment.

Comment: These results suggest that CoQ10 can improve renal function and reduce the need for dialysis in patients with chronic renal failure. The public-health implications of this study are enormous, considering that chronic renal failure is a serious and debilitating disease and that the annual cost of dialysis in the United States is more than $22 billion.

According Dr. Singh, to the lead author of this study (Interview with Kirk Hamilton; Clinical Pearls News, August, 2001, pp. 128-9), CoQ10 is usually effective if pre-treatment urine output, with or without furosemide, is at least 1,000 ml/day. However, if urine output is less than 500 ml/day, then CoQ10 usually does not work, presumably because the kidney has been irreversibly damaged. Dr. Singh recommends that that all patients with renal failure take 180 mg/day of water-soluble CoQ10 if their urine output is greater than 500 ml/day on dialysis. If urine output increases to 1,000 ml/day within 12 weeks, then CoQ10 is likely to be effective. Patients should be able to stop dialysis within 12-48 weeks if the urine output goes above 1,500 ml/day. If urine output does not increase in 12 weeks, then CoQ10 is unlikely to be effective.

While the mechanism by which CoQ10 improves renal function is not clear, it may work by improving cellular bioenergetics. Large controlled trials are urgently needed.

Singh RB, et al. Randomized, double-blind, placebo-controlled trial of coenzyme CoQ10 in patients with end-stage renal failure. J Nutr Environ Med 2003;13:13-22

Six children (aged 10-13 years) with steroid-responsive idiopathic nephrotic syndrome were studied. Prednisone was discontinued and a hypoallergenic elemental diet was given. After proteinuria had decreased to 500 mg per 24 hours or less on consecutive days (usually within 3-10 days), patients were challenged with cow's milk. Cow's milk challenge resulted in the return of significant proteinuria, edema, and decreased urine volume, together with a decrease in serum IgG concentrations in four patients. An acute alteration of plasma C3 complement component accompanied milk challenge in all six patients. Intradermal skin testing with cow's milk extract was positive in all six patients.

Comment: These results suggest that food allergy, particularly allergy to cow's milk, plays a role in the pathogenesis of idiopathic steroid-responsive nephrotic syndrome. Although the sample size was small, other studies have confirmed that food allergy is a factor in at least some cases of nephrotic syndrome. An elimination diet, followed by individual food challenges, can often be used to identify foods to which a person is sensitive. In patients with nephrotic syndrome, serial urinary protein measurements can help determine whether the diet is effective and what the offending foods are. Patients who are able to control their nephrotic syndrome with dietary modification alone will be spared the adverse effects of long-term prednisone use.

Sandberg DH, et al. Severe steroid-responsive nephrosis associated with hypersensitivity. Lancet 1977;1:388-391.

Twenty healthy male volunteers were randomly assigned to receive a single 50,000-IU dose of either vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol). Similar increases were seen in the serum concentration of the administered vitamins, indicating equivalent absorption. Both treatments also produced similar initial increases in serum 25-hydroxyvitamin D (25OHD) concentrations (the assay measured both 25OHD2 and 25OHD3) over the first 3 days. However, 25OHD levels continued to rise in the vitamin D3 group, peaking at 14 days, whereas 25OHD levels fell rapidly in the vitamin D2 group and were not different from baseline at 14 days. The area under the serum concentration-time curve (AUC) from day 0 to 28 for vitamin D2 was only 29.4% that for vitamin D3. Calculated AUC (from day 0 to infinity) indicated an even greater differential, with the potency of vitamin D2 being only 10.6% that of vitamin D3.

Comment: Vitamin D3 is the form of vitamin D that occurs naturally in the human body, whereas vitamin D2 is produced by irradiating yeast with ultraviolet light. Since the 1930s, it has been generally assumed that vitamin D3 and vitamin D2 are equally effective in humans. This assumption is based mainly on anti-rachitic bioassays. However, physicians frequently find that oral administration of vitamin D2 in doses of 50,000 IU taken with frequencies ranging from 3 times a week to once every 2 months produces little or no change in serum 25-hydroxyvitamin D (25OHD) concentrations. The results of the present study indicate that the potency of vitamin D2 may be as low as 10% that of vitamin D3, and clinical observations suggest that there is considerable individual variation in the response to vitamin D2. Considering that vitamin D3 is the form of vitamin D that occurs naturally in humans, vitamin D3 should be used for routine vitamin D supplementation. On the other hand, patients with hypoparathyroidism or other vitamin D-responsive conditions that are well controlled on high-dose vitamin D2 should probably not have their regimens changed. When changing from vitamin D2 to vitamin D3, it is important to remember the differences in potency, and to monitor serum concentrations of 25-OHD until the optimal dose is achieved.

Armas LAG, et al. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab 2004;89:5387-5391.

Alkylresorcinols (ARs) are a class of phenolic lipids present in high amounts in wheat bran and rye bran. The concentrations of ARs in whole wheat and whole rye are 320-1,430 mcg/g and 360-3,200 mcg/g, respectively, but these compounds are not present in refined flour. Because ARs are amphiphilic, they can form monolayers and be incorporated into phospholipid membranes. ARs have structural similarities to tocopherols and tocotrienols.

In the present study, rats were fed one of four different levels of ARs for 4 weeks: 0 (control), 1, 2, and 4 g/kg of diet. Compared with the control diet, each of the AR diets significantly increased the concentration of gamma-tocopherol in liver and lungs (p < 0.05). In vitro studies using HepG2 cells suggested that ARs increase the concentration of gamma-tocopherol by inhibiting its metabolism.

Comment: A growing body of evidence suggests that gamma-tocopherol (one of the naturally occurring forms of vitamin E), can help prevent heart disease and cancer. The capacity of a constituent of whole grains to increase tissue levels of gamma-tocopherol might explain in part the cardioprotective and anticancer effects of whole grains. Of course, the higher concentrations of magnesium, folic acid, vitamin B6, choline, betaine, zinc, copper, vitamin E, and fiber in whole grains than in refined flour presumably also play a role in the health benefits of whole grains. The more new biologically active components we discover in whole foods, the more it becomes apparent that we will never be able to duplicate nature with synthetic nutrient supplements.

Ross AB, et al. Cereal alkylresorcinols elevate gamma-tocopherol levels in rats and inhibit gamma-tocopherol metabolism in vitro. J Nutr 2004;134:506-510.

One hundred-nine pregnant women living in Mexico City who were not taking vitamin supplements were randomly assigned to receive, in double-blind fashion, 100 mg/day of vitamin C or placebo. Treatment was begun in the 20th week of gestation. The mean dietary vitamin C intakes were 63 and 68 mg/day in the placebo and vitamin C groups, respectively. The incidence of premature rupture of the chorioamniotic membranes (PROM) was 24.6% in the placebo group and 7.7% in the vitamin C group (relative risk = 0.26; 95% confidence interval, 0.078-0.837).

Comment: PROM affects 10-20% of all pregnancies. It is the main known cause of preterm delivery and is associated with increased rates of neonatal and maternal morbidity and mortality. Vitamin C plays a role in the synthesis of collagen, which is involved in maintaining the mechanical strength of the chorioamniotic membranes.

The results of the present study indicate that supplementing with 100 mg/day of vitamin C beginning in the 20th week of gestation decreased the incidence of PROM by 74% in Mexican women with borderline-low dietary vitamin C intake. Whether vitamin C supplementation would reduce the incidence of PROM in women whose dietary intake of vitamin C is higher should be the topic of future investigation.

Casanueva E, et al. Vitamin C supplementation to prevent premature rupture of the chorioamniotic membranes: a randomized trial. Am J Clin Nutr 2005;81:859-863.

Forty graduate students attending a Super Bowl party were escorted in alternating order to one of two identical buffet tables on opposite sides of an adjoining room and were offered snacks before the game. The tables contained identical amounts of high-energy snacks, but the size of the bowls in which the snacks were offered differed between the tables: two large (4-L capacity) bowls versus four small (2-L capacity) bowls. Compared with participants serving themselves from small bowls, those serving from large bowls took 53% (146 calories) more and consumed 56% (142 calories) more calories (p = 0.02 and 0.01, respectively).

Comment: The results of this study demonstrate that small environmental cues, such as the size of a serving bowl, can influence the amount of food a person consumes. Previous studies have shown that children tend to overeat when they are served a large amount of food on a plate, whereas they consume less when the plate contains less food. Other research has found that the size of a salt shaker hole has a significant influence on the amount of salt a person puts on his or her food. According to the results of the present study, people might become healthier if the potato chips were served in a thimble and the fruits and vegetables in a boxcar.

Wansink B, Cheney MM. Super Bowls: serving bowl size and food consumption. JAMA 2005;293:1727-1728.

Eighty patients (mean age, 63 years) with chronic obstructive pulmonary disease (COPD) were randomly assigned to receive, in double-blind fashion, 9 g/day of polyunsaturated fatty acids (PUFAs) (providing daily 760 mg of gamma-linolenic acid, 1,200 mg of alpha-linolenic acid, 700 mg of eicosapentaenoic acid, and 340 mg of docosahexaenoic acid) or placebo (80% palm oil and 20% sunflower oil) during an 8-week rehabilitation program. All capsules contained 3.5 mg/g of vitamin E. Both groups had similar increases in body weight, fat-free mass (FFM), and muscle strength. The peak load of the incremental exercise test increased more in the PUFA group than in the placebo group (p = 0.009), even after adjustment for FFM. The duration of the constant work rate test also increased more in patients receiving PUFA (p = 0.023). The positive effects of PUFA could not be attributed to a decrease in systemic levels of CRP, IL-6 and TNF-alpha.

Comment: These results suggest that supplementation with a mixture of fatty acids improved exercise capacity in patients with COPD. Although some of these fatty acids have been shown to have anti-inflammatory effects, the clinical improvement in this study did not seem to be due to a reduction in inflammation.

Patients with COPD are frequently malnourished, or become malnourished as a result of increased metabolic demands related to the disease. Malnutrition in patients with COPD can decrease respiratory-muscle and lung function, and reduce defense mechanisms in the lungs. A comprehensive nutritional program that includes protein, calories, vitamins, and minerals may improve the clinical status of patients with COPD. The results of the present study indicate that essential fatty acids are also important for people with chronic lung disease.

Broekhuizen R, et al. Polyunsaturated fatty acids improve exercise capacity in chronic obstructive pulmonary disease. Thorax 2005;60:376-382.