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From the Townsend Letter
May 2007


Literature Review & Commentary
by Alan R. Gaby, MD

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Quercetin for hypertension?
Rats were fed a standard diet or a diet high in fat and sucrose (HFS) containing varying amounts of quercetin (0, 0.02, 0.07, 0.2, or 0.5%). In rats fed no quercetin, the mean systolic blood pressure was significantly higher with the HFS than with the standard diet. The increase in blood pressure induced by the HFS diet was significantly blunted by all doses of quercetin, but 0.5% quercetin was significantly more effective than the other doses. Quercetin appeared to work by increasing the synthesis of nitric oxide, which functions as a vasodilator.

Comment: Quercetin is a flavonoid that is present in many different plant foods. The concentration of quercetin is particularly high in onions (284-486 mg/kg) and is moderately high in kale, broccoli, tea, and apples (21-110 mg/kg). Quercetin inhibits the enzyme aldose reductase in vitro at concentrations similar to those achievable in vivo with oral administration. Compounds that inhibit aldose reductase prevent the accumulation of sorbitol in cells and would therefore be expected to slow the development of complications of diabetes such as retinopathy and neuropathy. The present study suggests that quercetin also has an antihypertensive effect. In a previous study, ingestion of an onion extract lowered blood pressure in hypertensive patients. While the active ingredient was thought to be a prostaglandin present in onions, the new study suggests that quercetin may also contribute to the blood pressure-lowering effect of onions. Quercetin may also contribute, along with potassium, magnesium, and essential fatty acids, to the antihypertensive effect of a diet high in fruits and vegetables.

Yamamoto Y, Oue E. Antihypertensive effect of quercetin in rats fed with a high-fat, high-sucrose diet. Biosci Biotechnol Biochem. 2006;70:933-939.

Chromium improves insulin sensitivity in polycystic ovary syndrome
In a study of five obese women with polycystic ovary syndrome (PCOS), supplementation with 1,000 mcg/day of chromium (as chromium picolinate) for two months, with no change in diet or activity level, resulted in a 38% increase in the mean glucose disposal rate (as determined by the euglycemic hyperinsulinemic clamp method). The increase in the glucose disposal rate suggests an improvement in insulin sensitivity.

Comment: PCOS is a common endocrine disorder characterized by infertility, anovulation, amenorrhea, hirsutism, acne, male pattern baldness, obesity, sleep apnea, and enlarged ovaries with multiple cysts. Biochemical and endocrine abnormalities in women with this condition include elevated levels of androgens and hyperinsulinemia (which results from insulin resistance). Hyperandrogenism is responsible for many symptoms of PCOS, including reproductive and menstrual abnormalities, hirsutism, and acne. Elevated androgen levels, in turn, appear to be due in part to hyperinsulinemia, which triggers an increase in androgen production. Interventions that improve insulin resistance may reverse some of the manifestations of PCOS. The results of the present study indicate that chromium supplementation may be beneficial for women with PCOS.

Lydic ML, et al. Chromium picolinate improves insulin sensitivity in obese subjects with polycystic ovary syndrome. Fertil Steril. 2006;86:243-246.

Whole flaxseed lowers glucose and triglyceride levels
Nine overweight, hypertensive volunteers (mean age, 55 years) with glucose intolerance were randomly assigned to consume 40 g per day of flaxseed or wheat bran in the form of ground grain or bread for 12 weeks. After a four-week washout period, each person consumed the alternate supplement for an additional 12 weeks. During flaxseed supplementation, the mean fasting serum glucose concentration decreased by 16% (p = 0.02 compared with baseline, p = 0.04 compared with wheat bran), and the mean fasting serum triglyceride concentration decreased from 202 mg/dl to 150 mg/dl (25% decrease; p = 0.02 compared with wheat bran). Total serum cholesterol levels did not change.

Comment: This study indicates that consumption of flaxseeds lowers glucose and triglyceride levels in people with impaired glucose tolerance. These changes would be expected to reduce the risk of cardiovascular disease, which is elevated in glucose-intolerant patients. While the active ingredient was not identified in this study, it would be a mistake to assume that flaxseed oil (a popular supplement) would necessarily provide the same benefits as those observed with whole ground flaxseed.

Flaxseed meal contains a vitamin B6 antagonist, and consumption of large amounts of flaxseed meal resulted in vitamin B6 deficiency in animal studies. To be on the safe side, people who regularly consume flaxseed should supplement with a multivitamin or a B-complex vitamin.

Rhee Y, Brunt A. Pilot study: Flaxseed supplementation was effective in lowering serum glucose and triacylglycerol in glucose intolerant people
. J Am Neutraceutical Assoc. 2006;9(1):28-34.

Vitamin B12 for diabetic retinopathy
Fifteen patients with type 1 diabetes injected 100 mcg of vitamin B12 subcutaneously, along with insulin, each day for two years. The mean duration of diabetes prior to vitamin B12 treatment was 11.8 years. All patients had retinopathy at the time of the study. After one year of treatment, signs of retinopathy had disappeared in seven of 15 patients. After two years, eight of 15 were free of retinopathy. Some patients reported an increased feeling of well-being during the study. No adverse effects were seen.

Vitamin B12 was effective only in young diabetics with incipient hemorrhagic retinopathy whose disease started before age ten. In a group of 22 adult patients with diabetes, vitamin B12 was not beneficial.

Comment: Although the lack of a control group makes it difficult to draw firm conclusions, vitamin B12 injections are safe and should therefore be considered for young patients with type 1 diabetes. This study, which was performed nearly fifty years ago, is largely unknown to the medical profession. Because it is simple, safe, and inexpensive, administration of vitamin B12 to prevent and treat diabetic neuropathy clearly warrants further research. Vitamin B12 injections have also been reported to be beneficial in the treatment of diabetic neuropathy in adults.

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

Evening primrose oil for diabetic neuropathy
Twenty-two patients with type 1 (n = 10) or type 2 (n = 12) diabetes and distal diabetic polyneuropathy confirmed both clinically and by objective nerve function studies were randomly assigned to receive, in double-blind fashion, evening primrose oil (EPO; 2 g twice a day, providing 360 mg per day of gamma-linolenic acid) or placebo for six months. Compared with placebo, the EPO group showed significant improvement in neuropathy symptom scores (p < 0.001) and in various measures of motor and sensory nerve function (including median nerve and peroneal nerve motor conduction velocity and median and sural sensory nerve action potential amplitude).

Comment: These results indicate that evening primrose oil is beneficial in the treatment of distal diabetic polyneuropathy. The main active ingredient is probably gamma-linolenic acid (GLA), since pure esterified GLA has been shown to reduce the severity of experimentally induced diabetic neuropathy in rats. Alpha-lipoic acid has also been found in both human and animal studies to be effective against diabetic neuropathy. In a study in rats, the combination of alpha-lipoic acid and GLA ester was more effective than either treatment alone.

Jamal GA, Carmichael H. The effect of gamma-linolenic acid on human diabetic peripheral neuropathy: A double-blind placebo-controlled trial. Diabet Med. 1990;7:319-323.

Eggs are good for the eyes
Thirty-three elderly men and women (mean age, 80 years) consumed a diet low in lutein and zeaxanthin, with no eggs, for four weeks. They were then randomly assigned to consume one egg per day or no eggs for five weeks. After a four-week washout period, they consumed the alternate diet for an additional five weeks. Compared with baseline, egg consumption resulted in significant increases in the mean serum concentrations of lutein (+26%; p < 0.001) and zeaxanthin (+38%; < 0.001). Egg consumption had no significant effect on serum concentrations of total and LDL cholesterol.

Comment: A growing body of evidence indicates that lutein and zeaxanthin may help prevent age-related macular degeneration. Major food sources of these carotenoids include spinach and other dark green vegetables, corn, and egg yolk. While the concentration of lutein and zeaxanthin in egg yolk is not especially high, the lutein and zeaxanthin it contains appears to be particularly well-absorbed. Thus, eating moderate amounts of eggs may be an efficient way to obtain these important carotenoids.

Goodrow EF, et al. Consumption of one egg per day increases serum lutein and zeaxanthin concentrations in older adults without altering serum lipid and lipoprotein cholesterol concentrations. J Nutr. 2006;136:2519-2524.

Cinnamon for type 2 diabetes
Sixty patients (mean age, 52.2 years) with type 2 diabetes who were not on insulin therapy were randomly assigned to receive (blinding not specified) cinnamon at a dose of 1, 3, or 6 g per day or placebo for 40 days. Compared with baseline, all three doses of cinnamon reduced the mean fasting serum glucose (18-29%), triglyceride (23-30%), LDL-cholesterol (7-27%), and total-cholesterol (12-26%) levels; the responses to the three doses were similar. The reductions in fasting glucose and triglyceride levels were all significant (p < 0.05) compared with placebo, and some but not all the reductions in total- and LDL-cholesterol levels were significant compared with placebo.

Comment: Extracts of cinnamon have been shown to increase in vitro glucose uptake. In addition, cinnamon extracts are believed to aid in triggering the insulin cascade. The results of the present study demonstrate that daily supplementation with 1 g of cinnamon can improve glucose and lipid levels in patients with type 2 diabetes.

Two other studies have investigated the effect of cinnamon in patients with type 2 diabetes. In one of these studies, cinnamon was somewhat less effective than in the present study (Eur J Clin Invest. 2006;36:340-344); in the other study, cinnamon was not beneficial compared with placebo (J Nutr. 2006;136:977-980). It is not clear why the results of these studies differed.

Other than occasionally causing oral mucosal reactions, cinnamon appears to be safe. Therefore, a therapeutic trial would seem reasonable for patients with type 2 diabetes.

Khan A, et al. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care. 2003;26:3215-3218.

Adverse effect of red yeast rice
A 61-year-old woman with a history of myopathy due to simvastatin developed severe myalgia in association with markedly elevated serum creatine kinase concentrations while taking unspecified doses of red yeast rice (rice that has been fermented by the red yeast Monascus purpureus) for hyperlipidemia. After red yeast rice was discontinued, symptoms resolved, and the creatine kinase level became normal.

Comment: Red yeast rice contains a wide array of chemicals that are structurally similar to, and have the same mechanism of action as, prescription HMG CoA-reductase inhibitors (statin drugs) used to treat hypercholesterolemia. Myopathy and myalgia are common side effects of prescription statin drugs. While red yeast rice seems to be well-tolerated in most cases, it has the potential to cause the same adverse effects in susceptible people as statins do. People taking red yeast rice should therefore watch for the development of muscle symptoms and should discontinue treatment if this side effect occurs.

Myalgias associated with the use of HMG CoA-reductase inhibitors may be due in part to a deficiency of coenzyme Q10, the synthesis of which is inhibited by these compounds. However, other factors must be involved as well, because supplementation with coenzyme Q10 is not universally successful in preventing this side effect.

Mueller PS. Symptomatic myopathy due to red yeast rice. Ann Intern Med. 2006;145:474-475.

Alan R. Gaby, MD

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