When spontaneously hypertensive rats were maintained on 40% of an otherwise typical diet, their mean life span increased from 18 months to over 30 months. The mean life span of normotensive rats that were similarly food restricted increased from 24 months to over 32 months. Food restriction also prevented the development of end-organ damage associated with high blood pressure.

Comment: The capacity of food restriction to increase the life span of experimental animals has been known for more than 50 years. Currently, restriction of energy intake is the only intervention that has clearly been shown to extend life span in animal models. Energy restriction prevents the early loss of T cell-mediated immune function and delays the loss of various endocrine functions. Energy restriction also modulates oxidative stress and inhibits the development of autoimmune renal diseases and various age-related diseases (including cancers) in animals. The beneficial effect of energy restriction appears to be above and beyond that which would be expected from preventing obesity.

While restricting food intake is certainly not an easy undertaking for many people, emphasizing low-calorie foods such as fruits and vegetables will usually result in lower total energy intake. Eating small, frequent meals also helps some people avoid going on high-calorie binges.

Lloyd T. Food restriction increases life span of hypertensive animals. Life Sci 1984;34:401-407.

Twenty healthy women (mean age, 55.3 years) with photoaged skin (damage due to chronic sun exposure) were randomly assigned to apply, in double-blind fashion, a 5% vitamin C cream on one side of their lower neck and arms and a placebo cream on the other side, once a day for six months. Outcome was assessed by a "global score" (a composite score that consisted of the sum of six items: hydration, roughness, laxity, suppleness, fine wrinkles, and coarse wrinkles). Clinical examination by a dermatologist, as well as self-assessment by the volunteers, revealed a significant improvement in global score on the vitamin C-treated side compared with the control side. Application of vitamin C resulted in a significant improvement in both fine and coarse wrinkles. Ultrastructural evidence of elastic-tissue repair confirmed the clinical improvement in the vitamin C group. The treatment was well tolerated.

Comment: This study demonstrates that that topical application of a 5% vitamin C cream is an effective and well-tolerated treatment for photoaged skin. Vitamin C has been shown to reduce oxidative stress in the skin, and also stimulates dermal fibroblasts to synthesize collagen, which may be of value in reversing photoaging. Topical application of vitamin C achieves higher skin concentrations than are obtainable with oral administration. A number of different vitamin C preparations for topical administration are commercially available.

Humbert PG, et al. Topical ascorbic acid on photoaged skin. Clinical, topographical and ultrastructural evaluation: double-blind study vs. placebo. Exp Dermatol 2003;12:237-244.

Two hundred seventy-eight Iranian girls (aged 15-17 years) with primary dysmenorrhea were randomly assigned to receive, in double-blind fashion, 200 IU of vitamin E (type not specified) twice a day or placebo, beginning 2 days before the expected start of menstruation and continuing through the first 3 days of bleeding. Treatment was continued for a total of 4 consecutive menstrual periods. The median pain score (on a scale of 0-10, with 10 being the worst) at 2 months was 3 in the vitamin E group and 5 in the placebo group (p < 0.001). At 4 months, the respective values were 0.5 and 6 (p < 0.001). The median duration of pain at 2 months was 4.2 hours in the vitamin E group and 15.4 hours in the placebo group (p < 0.001). At 4 months, the respective values were 1.6 and 16.7 hours (p < 0.001). The mean amount of blood loss was significantly less at 2 months (-23%; p < 0.001) and 4 months (-34%; p < 0.0001) in the vitamin E group than in the placebo group.

Comment: Women with dysmenorrhea have relatively high concentrations of prostaglandin F2alpha in menstrual fluid, and suppression of prostaglandin synthesis is an established treatment for dysmenorrhea. Vitamin E inhibits the release of arachidonic acid and the conversion of arachidonic acid to prostaglandins via actions on phospholipase A2 and cyclooxygenase, respectively. The results of this study suggest that vitamin E supplementation can reduce both the pain of primary dysmenorrhea and the amount of menstrual blood loss. Whether or not the results of this study from Iran would apply to those consuming a western diet was not addressed in this study. However, an earlier study showed that vitamin E reduced the symptoms of dysmenorrhea in British college students (Lancet 1955;1:844-847).

Ziaei S, et al. A randomised controlled trial of vitamin E in the treatment of primary dysmenorrhoea. BJOG 2005;112:466-469.

Twenty-eight patients (mean age, 56 years) with moderately severe acute pancreatitis were randomly assigned to receive a standard enteral formula (controls) or a special formula supplemented with 3.3 g/day of omega-3 fatty acids from fish oil for 5-7 days. Compared with controls, patients receiving fish oil had a significantly shorter mean length of hospital stay (13.1 vs. 19.3 days; p < 0.05) and of jejunal feeding (10.6 vs. 17.6 days; p < 0.05). Complications developed in 42% of treated patients and 64% of control patients (difference not significant).

Comment: These results indicate that the use of an enteral formula enriched with fish oil significantly reduced the length of hospital stay and the time required for jejunal feeding in patients with acute pancreatitis. Omega-3 fatty acids presumably work by modulating eicosanoid synthesis, thereby reducing the inflammatory response.

Lasztity N, et al. Effect of enterally administered n-3 polyunsaturated fatty acids in acute pancreatitis - a prospective randomized clinical trial. Clin Nutr 2005;24:198-205.

Fifty patients (mean age, 60 years) with carotid intima-media thickness (IMT)  1 mm, which is associated with an increased risk of cerebral ischemia, were randomly assigned to receive daily, in double-blind fashion, either 1) 2.5 mg of folic acid, 25 mg of vitamin B6, and 0.5 mg of vitamin B12, or 2) placebo for 1 year. In the active-treatment group, the mean plasma homocysteine concentration decreased from 10.50 to 6.56 micromol/L (p < 0.0001), but remained unchanged in the placebo group (10.76 vs. 10.45 micromol/L). Mean IMT in the active-treatment group decreased from 1.50 to 1.42 mm (p = 0.034), a change suggestive of a regression of atherosclerosis. In contrast, mean IMT increased from 1.47 to 1.54 mm in the placebo group (< 0.02 for the difference in the change between groups).

Comment: In this study, supplementation with folic acid, vitamin B6, and vitamin B12 significantly reduced carotid intima-media thickness in patients at risk of cerebral ischemia. While some of this improvement may have been due to a reduction in homocysteine levels, the effect appeared to be at least partly independent of both baseline plasma homocysteine concentrations and the change in homocysteine levels during treatment. Vitamin B6, in particular, has actions unrelated to homocysteine metabolism that might be expected to improve vascular health, such as enhancement of endothelial-tissue integrity and inhibition of platelet aggregation.

Till U, et al. Decrease of carotid intima-media thickness in patients at risk to cerebral ischemia after supplementation with folic acid, vitamins B6 and B12. Atherosclerosis 2005;181:131-135.

Twenty-three men and 23 women (aged 45-65 years) with midlife-onset major or minor depression who were not receiving antidepressant medications were randomly assigned to receive, in double-blind fashion, DHEA or placebo for 6 weeks. After a washout period of 1-2 weeks, each person received the alternate treatment for an additional 6 weeks. The dose of DHEA was 30 mg 3 times a day for 3 weeks, followed by 150 mg 3 times a day for 3 weeks. The mean score on the 17-Item Hamilton Depression Rating Scale (lower scores indicate less depression) was 13.5 at baseline, 7.5 after DHEA treatment, and 11.5 after placebo (p < 0.01 for the comparison of DHEA with both baseline and placebo). Similar results were seen using the Center for Epidemiologic Studies Depression Scale ratings. DHEA treatment also was associated with significant improvements in Derogatis Interview for Sexual Functioning scores relative to baseline and placebo. Thirteen patients who responded to DHEA elected to continue with an open-label trial of over-the-counter DHEA at a dose of 25-50 mg/day for 6-12 months. Of these 13 patients, 10 remained free of depression. No adverse effects were seen, with the exception of 1 woman who experienced a moderate increase in oily skin.

Comment: These results indicate that DHEA is an effective treatment for some patients with midlife-onset major or minor depression. The doses used in this study were extremely large relative to the presumed physiological requirement of approximately 5-15 mg/day for women and 10-30 mg/day for men. The long-term safety of such large doses has not been demonstrated, and there is the theoretical possibility that high-dose DHEA could promote the development of hormone-dependent cancers, such as breast and prostate cancer. Fortunately, doses closer to the physiological range were effective in the open-label portion of this trial, and also in some previous clinical trials, so it is probably not necessary to initiate treatment with supraphysiological doses.

DHEA does not appear to function as an antidepressant per se. However, if clinical depression is associated with DHEA deficiency, then supplementation with DHEA may be relieve the depression. As DHEA levels decline with age, it is reasonable to expect that some cases of midlife-onset depression are due to DHEA deficiency.

Schmidt PJ, et al. Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression. Arch Gen Psychiatry 2005;62:154-162.

Two hundred-eighty-three patients (mean age, 55 years) with subarachnoid hemorrhage due to an aneurysm were randomly assigned, within 4 days (mean, 35 hours) of the event, to receive, in double-blind fashion, intravenous magnesium sulfate (Mg) or placebo (normal saline). Mg was given as a continuous infusion at a dose of 64 mmol/day, and was continued until 14 days after occlusion of the aneurysm. The primary outcome measure was the incidence of delayed cerebral ischemia (defined as the occurrence of a new hypodense lesion on computed tomography compatible with clinical features of delayed cerebral ischemia). Compared with placebo, Mg treatment reduced the risk of delayed cerebral ischemia by 34% (relative risk = 0.66; 95% CI, 0.38-1.14). The number-needed-to-treat was 14, meaning that for every 14 patients treated, 1 episode of delayed cerebral ischemia would be prevented. After 3 months, Mg supplementation reduced the risk for poor outcome by 23%, a reduction that was of borderline statistical significance. Eighteen patients in the Mg group had an excellent outcome, as compared with 6 in the placebo group (p < 0.05).

Comment: Subarachnoid hemorrhage occurs at a young age and often has a poor outcome. Death or dependence occurs in approximately 70% of patients, and is attributed to delayed cerebral ischemia in approximately one-third of patients with a poor outcome. Hypomagnesemia occurs in more then 50% of patients with subarachnoid hemorrhage, and is related to the occurrence of delayed cerebral ischemia and poor outcome after 3 months. Magnesium reverses cerebral vasospasm and reduces infarct volume after experimental subarachnoid hemorrhage in rats. The results of the present study demonstrate that intravenous magnesium can reduce the incidence of delayed cerebral ischemia and subsequent poor outcome in patients with subarachnoid hemorrhage due to an aneurysm.

van den Bergh WM, et al. Magnesium sulfate in aneurysmal subarachnoid hemorrhage: a randomized controlled trial. Stroke 2005;36:1011-1015.

Some 1,257 patients with diabetic neuropathy were randomly assigned to receive, in double-blind fashion, placebo or acetyl-L-carnitine (ALC) at a dose of 500 or 1,000 mg 3 times a day for 1 year. Compared with placebo, the lower dose of ALC resulted in a significant improvement in the O'Brien rank score, a measure of sural nerve fiber numbers and regenerating nerve fiber clusters. The higher dose of ALC was non-significantly more effective than placebo. Compared with placebo, significant improvements were seen in both treatment groups in vibration perception. Compared with placebo, the mean pain score improved significantly more with high-dose ALC; the improvement with low-dose ALC was similar to that in the placebo group. Patients with type 2 diabetes were more likely to experience a reduction in pain from high-dose ALC than were patients with type 1 diabetes.

Comment: These results suggest that ALC can relieve pain and improve nerve fiber regeneration and vibration perception in patients with diabetic neuropathy. By some measures, a dose of 1,500 mg/day was more effective than 3,000 mg/day, but by other measures the higher dose was more effective. Therefore, if ALC is used to treat diabetic neuropathy, the dosage should be individualized according to the patient's response. Other treatments that have been reported to be beneficial for diabetic neuropathy include evening primrose oil, vitamin B12 injections, and vitamin B6.

Sima AAF, et al. Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: an analysis of two randomized placebo-controlled trials. Diabetes Care 2005;28:89-94.