Literature Review & Commentary

by Alan R. Gaby, MD

Vitamin B12 for Diabetic Retinopathy

Vitamin B12 (100 mcg per day) was given subcutaneously along with insulin for two years to 15 patients with type 1 diabetes. Mean duration of diabetes prior to vitamin B12 treatment was 11.8 years, and all patients had retinopathy at the time of the study. After one year of treatment, signs of retinopathy had disappeared in 7 of 15 patients. After two years, 8 of 15 patients were free of retinopathy. Aside from an increased feeling of well-being, there were no other observable effects of vitamin B12. The beneficial effect of vitamin B12 was evident only in young diabetics whose disease started before age 10 and who had incipient hemorrhagic retinopathy. Of 22 adult diabetics, none benefited from vitamin B12.

Comment

: Last year marked the 50th anniversary of the publication of this study. Although it was not a controlled trial, it would seem that adding some vitamin B12 to one of the daily insulin injections carries little risk and is of great potential benefit. Vitamin B12 is considered safe, even when given in large doses. However, there have been rare reports of anaphylactic reactions and rare cases of acneiform eruptions from the use of parenteral vitamin B12.

Kornerup T, Strom L. Vitamin B12 and retinopathy in juvenile diabetics. Acta Paediatr. 1958;47:646–651.

Do B Vitamins Enhance Bone Quality?

Femoral heads of 94 men and women (mean age, 70 years) who underwent elective hip arthroplasty were subjected to histomorphometric analysis and were tested for bone mineral density (BMD). Serum levels of folate, vitamin B6, and vitamin B12 were also measured. Vitamin levels were classified as high or low, depending on whether they were above or below the median. There was no significant difference in BMD between individuals with high or low levels of any of these vitamins. In contrast, histomorphometric analysis showed significantly lower trabecular thickness and trabecular area in patients with low serum folate levels than in those with high levels, and a significantly lower trabecular number (defined as the number of trabeculae per unit of length) in patients with low serum vitamin B6 levels than in those with high levels. These parameters were not influenced by vitamin B12 status.

Comment

: The results of this study suggest that assuring optimal folate and vitamin B6 status may improve bone quality. BMD is known to be associated with fracture risk, but many people with low BMD do not suffer fractures and many with high BMD do. The quality of the trabecular structure, as well as other aspects of bone quality, may be as important as BMD for determining fracture risk. Assuring optimal folate and vitamin B6 status may therefore reduce fracture risk, even though these vitamins may not influence BMD. In a previous double-blind trial, supplementation with folic acid (5 mg per day) and vitamin B12 (1.5 mg per day) decreased the incidence of hip fractures by 78% in elderly patients with hyperhomocysteinemia and a history of a stroke. These nutrients did not affect BMD, which suggests that the beneficial effect was due to an improvement in bone quality (JAMA. 2005;293:1082–1088).

Holstein JH, et al. Low serum folate and vitamin B-6 are associated with an altered cancellous bone structure in humans. Am J Clin Nutr. 2009;90:1440–1445.

Telling It Like It Ain’t

In this editorial, the writer points out that some “natural” weight loss products have been found to be contaminated with amphetamines. In addition, “dietary supplements” marketed for patients with diabetes, high cholesterol, or insomnia, as well as supplements designed to enhance sexual performance, have been found to be contaminated with prescription medications, anabolic steroids, experimental compounds, or drugs rejected by the FDA because of safety concerns. None of these substances were listed on the label. Some of the undeclared compounds present in these products have been linked to serious adverse events, including hypokalemia, dehydration, liver failure, addiction, and suicide.

Comment

: The addition of dangerous drugs to dietary supplements poses serious risks to unsuspecting consumers, and this type of criminal behavior should be prosecuted to the full extent of the law. My objection to this article is that it repeatedly used the word contaminated, when it would have been more appropriate to use adulterated. The difference between these terms is that the former usually implies inadvertent inclusion of unwanted materials, whereas the latter implies that the toxic substances were deliberately added. The title of this editorial, “American Roulette – Contaminated Dietary Supplements,” makes it sound like anyone who buys a bottle of vitamin C or St. John’s wort has a one in six chance of firing a bullet into his head. Some manufacturers in the natural foods industry need to do a better job with quality control, but that fact should not be lumped in with the fact that dangerous chemicals are deliberately being sneaked into dietary supplements by unscrupulous people who sell their products mainly over the Internet.

Cohen PA. American roulette – contaminated dietary supplements. N Engl J Med. 2009;361:1523–1525.

Mild Iodine Deficiency Impairs Cognitive Function

One hundred eighty-four children (aged 10–13 years) in New Zealand were randomly assigned to receive, in double-blind fashion, 150 mcg per day of iodine or placebo for 28 weeks. At baseline, the children were mildly iodine-deficient (median urinary iodine concentration, 63 mcg/L). Iodine supplementation significantly improved scores on two of four tests of cognitive function, and the overall cognitive score was significantly greater in the iodine group than in the placebo group (p = 0.01). Iodine supplementation had no significant effect on the serum total thyroxine level.

Comment

: It is well known that severe iodine deficiency during critical periods of brain development can lead to physical abnormalities and mental retardation. Less is known about the effects of mild iodine deficiency on neurological development and on cognitive function later in life. Mild iodine deficiency has become more common in recent years in some countries. Factors that may be responsible for the increasing prevalence of iodine deficiency include discontinuation of the use of iodine-containing sanitizers in the dairy industry, declining use of iodized salt, and increasing consumption of processed foods made with non-iodized salt (animal studies suggest that high intake of salt may interfere with iodine absorption).

The results of the present study indicate that iodine supplementation can improve cognitive function in children and adolescents with mild iodine deficiency. Iodine may work by reversing subtle hypothyroidism. Although no significant change in serum thyroxine levels were seen in this study, it is possible that iodine influences the metabolism of thyroid hormone or the binding of the hormone to its receptor. Only a small amount of iodine is needed to prevent iodine deficiency, and taking more of this trace mineral more is not necessarily better. Megadose iodine has been reported to cause thyroid dysfunction (hypothyroidism and, to a lesser extent, hyperthyroidism) as well as other side effects in some individuals.

Gordon RC, et al. Iodine supplementation improves cognition in mildly iodine-deficient children. Am J Clin Nutr. 2009;90:1264-1271.

Does drinking coffee prevent endometrial cancer?

The association between coffee drinking and endometrial cancer was examined in a prospective cohort study of 60,634 women participating in the Swedish Mammography Cohort. During 17.6 years of follow-up, 677 women were diagnosed with endometrial cancer. As compared with women consuming one cup or less of coffee per day, women drinking four or more cups per day had a 25% lower risk of developing endometrial cancer. The association persisted after adjustment for cigarette smoking, dietary factors, and other potential confounding variables. The reduction in risk associated with coffee consumption was restricted to overweight and obese women; coffee consumption was not associated with endometrial cancer risk in normal-weight women.

Comment

: Observational studies cannot prove cause-and-effect; it is possible that unidentified confounding factors (rather than coffee consumption per se) were responsible for the observed association between coffee intake and endometrial cancer. However, the possibility that drinking coffee prevents endometrial cancer is biologically plausible. Coffee consumption has been associated with an improvement in insulin resistance, and insulin resistance is believed to play a role in the pathogenesis of endometrial cancer. In addition, drinking coffee may stimulate bile flow, potentially enhancing the capacity of the liver to excrete xenobiotic and endogenously produced carcinogens. The possible protective effect of coffee against endometrial cancer must be weighed against the adverse effects of caffeine consumption in susceptible people, including fibrocystic breast changes, anxiety, insomnia, and palpitations. Additional research should investigate whether the risk reduction associated with drinking coffee extends to decaffeinated coffee.

Friberg E, Orsini N, Mantzoros CS, Wolk A. Coffee drinking and risk of endometrial cancer – a population-based cohort study. Int J Cancer. 2009;125:2413-2417.

Vitamin C deficiency is common

Serum vitamin C concentrations were measured in 7,277 individuals (aged 6 years or older) participating in the National Health and Nutrition Examination Survey 2003-2004. The overall prevalence of vitamin C deficiency was 7.1%. Smokers and low-income individuals had the highest prevalence of vitamin C deficiency.

Comment

: Vitamin C deficiency can lead to impaired immune function, increased risk of bleeding, gingival disease, arthralgias, increased susceptibility to cardiovascular disease, and various mental disorders including depression. The results of this study indicate that about one of every fourteen people living in the United States is deficient in vitamin C. Healthcare practitioners should be alert to the possibility that their patients may be deficient in vitamin C, particularly those who smoke cigarettes or do not consume many fruits and vegetables.

Schleicher RL, et al. Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003-2004 National Health and Nutrition Examination Survey (NHANES). Am J Clin Nutr. 2009;90:1252-1263.

Could eating eggs prevent macular degeneration?

Fifty-two individuals (mean age, 69 years) who were taking a cholesterol-lowering statin drug consumed two egg yolks per day for five weeks, followed by no egg yolks for four weeks, then four egg yolks per day for five weeks. In the group as a whole, there was a nonsignificant trend toward an increase in macular pigment optical density (MPOD) by the end of the trial. Among individuals with initially low MPOD, MPOD increased significantly (p < 0.05) after consumption of four egg yolks per day and increased nonsignificantly after consumption of two egg yolks per day (p = 0.06).

Comment

: Egg yolks are a rich source of bioavailable lutein, a carotenoid that has been found in high concentrations in the macular pigment of the retina. There is evidence that the lutein filters the toxic blue-light portion of the sun’s rays, and thereby protects the macula from sunlight-induced damage. Higher MPOD implies a greater content of lutein (or a greater content of zeaxanthin, a related carotenoid) in the macula, and has been associated with a decreased risk of developing age-related macular degeneration. A similar protective effect could presumably be achieved by eating other foods that are high in lutein or zeaxanthin, such as spinach, kale, and corn.

Vishwanathan R, et al. Consumption of 2 and 4 egg yolks/d for 5 wk increases macular pigment concentrations in older adults with low macular pigment taking cholesterol-lowering statins. Am J Clin Nutr. 2009;90:1272-1279.

Fish oil does not interact with aspirin and clopidogrel (Plavix)

The authors of this report retrospectively reviewed the medical records of 364 patients (mean age, 61 years), most of whom had coronary artery disease. All patients were taking aspirin (mean dose, 161 mg per day) and clopidogrel (mean dose, 75 mg per day), and half of the patients were also taking high-dose fish oil (mean dose, 3 g per day). During a mean follow-up period of 33 months, one major bleeding episode occurred in the group taking fish oil and no major bleeding episodes occurred in the group not taking fish oil (p = 1.0). Four minor bleeding episodes occurred in the fish oil group and seven minor bleeding episodes occurred in the group not taking fish oil (p = 0.5).

Comment

: Aspirin, clopidogrel, and fish oil each inhibit platelet aggregation. It is therefore possible that taking all of these substances together would increase the risk of bleeding complications. However, the results of this study suggest that fish oil does not increase the risk of bleeding in patients taking aspirin and clopidogrel, and that people taking these medications can safely benefit from the cardioprotective effects of fish oil.

Watson PD, et al. Comparison of bleeding complications with omega-3 fatty acids + aspirin + clopidogrel versus aspirin + clopidogrel in patients with cardiovascular disease. Am J Cardiol. 2009;104:1052-1054.