December 1999 Blog with Durk and Sandy

LOW-DOSE L-ARGININE IMPROVES INSULIN SENSITIVITY

A recent study¹ tested the proposition that low-dose intravenous L-arginine supplements might improve insulin-mediated vasodilation and insulin sensitivity in patients with Type 2 diabetes (NIDDM, non-insulin-dependent diabetes mellitus). (Perhaps the study used intravenous L-arginine to assure control of the dose. However, L-arginine is also well absorbed orally.)

Adequate intracellular supplies of L-arginine are believed to be the rate-limiting step for adequate formation of nitric oxide (NO), which causes vasodilation when released by vascular endothelial cells. Though there appears to be plenty of L-arginine available, supplementation nevertheless has been shown to increase endothelium-dependent (NO) vasodilation in hypercholesterolemia. The 25 subjects were 9 with Type 2 diabetes, 9 obese, and 7 healthy controls. During the study, serum concentration of L-arginine was determined in six subjects (two in each group). The researchers found that impaired insulin-mediated vasodilation in obese or obese with Type 2 diabetes was restored by intravenous infusion of low-dose L-arginine. (93.6 mg/kg of L-arginine was administered over a three-hour period. This would be 6.55 grams for a 70-kg individual.) The authors report that this effect was observed at serum L-arginine concentrations far below the 4-7 mmol per liter that have been shown to be necessary for a direct vasodilatory action of L-arginine. Moreover, they found that insulin sensitivity was improved in the obese, those with Type 2 diabetes, and the healthy controls. The authors note that the improvement in insulin sensitivity observed in this study (-20%) is in agreement with the opposite effects observed after blockade of NO synthesis reported in another study. At the dose used, there was no effect on IGF-1 levels in the three groups.

The authors suggest that L-arginine's superoxide-scavenging properties (nitric oxide reacts with superoxide radicals to form peroxynitrite) may be the biochemical mechanism for the improvement of insulin sensitivity, because "every antioxidant investigated . . . improves insulin sensitivity in healthy subjects as well as in NIDDM subjects."

1. Wascher et al, "Effects of Low Dose L-Arginine on Insulin-Mediated Vasodilatation and Insulin Sensitivity," Eur. J. Clin. Invest. 27:690-695 (1997). 

WARM FEET PROMOTE RAPID ONSET OF SLEEP
In a new study of how long it takes to fall asleep, the authors find that the degree of dilation of blood vessels in the skin of the hands and feet is the best physiological predictor for the rapid onset of sleep.

Eight healthy young men were given melatonin or bright light, or both, in the evening, while another ten healthy young men were given a large, carbohydrate-rich meal in either the morning or evening, to test the effects on latency to sleep onset. The researchers found that the greater the distal vasodilation (i.e., the warmer the feet) in the late evening, the shorter was the time to fall asleep. The authors note that this vasodilation can be affected by a number of factors. For example, vasodilation can occur as a result of turning out the light, lying down (which redistributes heat from the core to the periphery), and endogenous increase of melatonin.

They suggest that "[s]ome sleep disorders (particularly those associated with aging and somatic illness) may be secondary to an inability to vasodilate and prepare the body for sleep."

Other possible ways to warm your feet and perhaps fall asleep faster include hot water bottles or an electric blanket at the foot of your bed, L-arginine plus choline supplementation, and niacin supplementation.

Krauchi et al, "Warm Feet Promote the Rapid Onset of Sleep," Nature 401:36-37 (1999).

OMEGA-3 FATTY ACIDS IN MANIC DEPRESSION
Omega-3 fatty acids (long-chain polyunsaturated fatty acids found in cold-water fish oils and in certain plants) are associated with a general dampening of signal-transduction pathways associated with the arachidonic acid cascade and other systems. The authors of a new study¹ hypothesized that omega-3 fatty acids would exhibit inhibitory effects on signal-transduction mechanisms in human neuronal membranes and that high-dose supplementation of omega-3 fatty acids might be an effective mood stabilizer in bipolar disorder (manic depression).

In a four-month, double-blind, placebo-controlled study, omega-3 fatty acids (9.6 g/d) were compared with placebo (olive oil) in 30 patients with bipolar disorder. (Subjects received a total daily omega-3 fatty acid dosage of 6.2 g of eicosapentaenoic acid and 3.4 g of docosahexaenoic acid.) Note: This is a pharmacological dose, much greater than the usual 1-2 grams per day taken by healthy individuals as a dietary supplement. One reason the authors mention for using this much is that there is a lack of data regarding the effective dosage of omega-3 fatty acids in mood disorders, and they didn't want to risk choosing a potentially ineffective low dose. They also note that similar doses have been used safely and effectively in other disease states (no particular disease states were mentioned).

The omega-3 fatty acid-treated group had a significantly longer period of remission from their symptoms as compared to the placebo group.

One problem was that, because of the fishy aftertaste (or fishy burps), 86% of the omega-3 fatty acids-treated group guessed that they were receiving active treatment, while 63% of the placebo group guessed correctly.

1. Stoll et al, "Omega-3 Fatty Acids in Bipolar Disorder, a Preliminary Double-blind, Placebo Controlled Trial," Arch. Gen. Psychiatry 56:407-412 (1999). 

WARM FEET PROMOTE RAPID ONSET OF SLEEP

In a new study of how long it takes to fall asleep, the authors find that the degree of dilation of blood vessels in the skin of the hands and feet is the best physiological predictor for the rapid onset of sleep.

Eight healthy young men were given melatonin or bright light, or both, in the evening, while another ten healthy young men were given a large, carbohydrate-rich meal in either the morning or evening, to test the effects on latency to sleep onset. The researchers found that the greater the distal vasodilation (i.e., the warmer the feet) in the late evening, the shorter was the time to fall asleep. The authors note that this vasodilation can be affected by a number of factors. For example, vasodilation can occur as a result of turning out the light, lying down (which redistributes heat from the core to the periphery), and endogenous increase of melatonin.

They suggest that "[s]ome sleep disorders (particularly those associated with aging and somatic illness) may be secondary to an inability to vasodilate and prepare the body for sleep."

Other possible ways to warm your feet and perhaps fall asleep faster include hot water bottles or an electric blanket at the foot of your bed, L-arginine plus choline supplementation, and niacin supplementation.

Krauchi et al, "Warm Feet Promote the Rapid Onset of Sleep," Nature 401:36-37 (1999).

OMEGA-3 FATTY ACIDS IN MANIC DEPRESSION

Omega-3 fatty acids (long-chain polyunsaturated fatty acids found in cold-water fish oils and in certain plants) are associated with a general dampening of signal-transduction pathways associated with the arachidonic acid cascade and other systems. The authors of a new study¹ hypothesized that omega-3 fatty acids would exhibit inhibitory effects on signal-transduction mechanisms in human neuronal membranes and that high-dose supplementation of omega-3 fatty acids might be an effective mood stabilizer in bipolar disorder (manic depression).

In a four-month, double-blind, placebo-controlled study, omega-3 fatty acids (9.6 g/d) were compared with placebo (olive oil) in 30 patients with bipolar disorder. (Subjects received a total daily omega-3 fatty acid dosage of 6.2 g of eicosapentaenoic acid and 3.4 g of docosahexaenoic acid.) Note: This is a pharmacological dose, much greater than the usual 1-2 grams per day taken by healthy individuals as a dietary supplement. One reason the authors mention for using this much is that there is a lack of data regarding the effective dosage of omega-3 fatty acids in mood disorders, and they didn't want to risk choosing a potentially ineffective low dose. They also note that similar doses have been used safely and effectively in other disease states (no particular disease states were mentioned).

The omega-3 fatty acid-treated group had a significantly longer period of remission from their symptoms as compared to the placebo group.

One problem was that, because of the fishy aftertaste (or fishy burps), 86% of the omega-3 fatty acids-treated group guessed that they were receiving active treatment, while 63% of the placebo group guessed correctly.

1. Stoll et al, "Omega-3 Fatty Acids in Bipolar Disorder, a Preliminary Double-blind, Placebo Controlled Trial," Arch. Gen. Psychiatry 56:407-412 (1999).