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Head Injury Study: Melatonin Is Neuroprotective

May 2004

LE Magazine May 2004
Head Injury Study: Melatonin Is Neuroprotective

Researchers at Israel’s Hebrew University in Jerusalem report that melatonin, a hormone with antioxidant activity that is produced in the brain’s pineal gland, is neuroprotective.*

Traumatic brain injury leads to massive production of reactive oxygen species, which in turn increases brain damage. Melatonin enhances brain antioxidants, including vitamin C, and blocks nuclear factor-kappa beta (NF-kB), a gene that regulates pro-inflammatory substances.

In the study, mice subjected to closed head injury were tested one hour later for neurological damage, using the Neurological Severity Score. They were then injected with melatonin or a substance in which melatonin is administered but which lacks melatonin. The Neurological Severity Score was reevaluated 24 hours later. The response to melatonin showed a bell-shaped curve—that is, neuroprotection was achieved in animals given 5 mg/kg but not in those given 1 mg/kg or 10 mg/kg.

Melatonin facilitated recovery and caused a twofold decrease in brain lesion size.

Treatment with 5 mg/kg produced a sustained (four-day) increase in total antioxidants (yet to be identified) and a higher content of vitamin C in the brain cortex. Antioxidant levels were unaffected by the neuroprotective endocanabinoid 2AG given after injury, underscoring the specificity of melatonin-induced neuroprotection.

Melatonin blocks the AP-1 and NF-kB genes that are activated in closed head injury. NF-kB regulates numerous genes, including production of pro-inflammatory cytokines that interact with free radicals and exacerbate brain injury.

The authors suggest that the use of melatonin as a therapeutic strategy may stimulate beneficial antioxidants and inhibit destructive responses such as inflammation.

—Carmia Borek, PhD


* Beni SM, Kohen R, Reiter RJ, Tan DX, Shohami E. Melatonin-induced neuroprotec- tion after closed head injury is associated with increased brain antioxidants and attenuated late-phase activation of NF-kappaB and AP-1. FASEB J. 2004 Jan;18(1):149-51. Epub 2003 Nov 03.

Study Links Depression to Omega-3 Deficiency

In recent years, scientists have discovered that chemical balances in the brain influence depression. Some antidepressant drugs, for example, modify the reuptake of the neurotransmitter serotonin, helping to improve mood. New research has shown that the composition of fatty acids in the diet can have an effect on brain-receptor function and signal transmission, suggesting that the amount and types of fat eaten can affect vitality and happiness.

A team of researchers at the Erasmus University Medical Centre in Rotterdam, Netherlands, looked at the association between depression and the fatty-acid composition of blood plasma in 264 subjects with depressive symptoms and 461 randomly selected reference subjects who screened negative for depression.* After an overnight fast, all of the participants had their blood drawn, which was then analyzed for omega-3 and omega-6 fatty acids and for C-reactive protein (an indicator of immune response).

The Dutch scientists found a correlation between the intake of fatty acids and depressive disorders in the elderly after adjustment for demographic and biological factors. As the amount of omega-3 fatty acids (such as EPA and DHA) increased in the participants’ diets relative to omega-6 acids (like linoleic acid and arachidonic acid), the incidence of depression declined.

Moreover, the strength of this association grew as C-reactive protein levels dropped. The researchers believe that this is because people with impaired immune systems are sicker and more likely to be depressed, so diet is not as big a factor in determining their mood. The healthier you are, the more your dietary choices influence your frame of mind. While it has been known for some time that eating cold-water fish and taking fish-oil capsules are good for the heart, it now appears that consuming more omega-3s can make one happier as well.


* Tiemeier H, van Tuijl HR, Hofman A, Kiliaan AJ, Breteler MM. Plasma fatty acid composition and depression are associated in the elderly: the Rotterdam study. Am J Clin Nutr. 2003 Jul;78(1):40-6.

Testosterone Supplementation Found Safe in New Report

Last November, the Institute of Medicine issued a report on testosterone and aging (see “Testosterone Attacked by the Media,” February 2004) that was cautious, and in some instances critical, of the use of testosterone supplementation in aging men. A new study challenges issues raised in that report concerning the safety of testosterone supplementation with regard to prostate cancer and heart disease.*

The Institute of Medicine report voiced concern that testosterone supplementation may cause prostate cancer, though to date no scientific study has demonstrated such a link. Likewise, because heart disease is more common in men than women, some have surmised that testosterone could be a risk factor for heart disease.

According to researchers at Boston’s Beth Israel-Deaconess Medical Center who conducted an exhaustive review of more than 70 studies on the safety of testosterone replacement therapy, testosterone supplementation is not associated with an increased risk of prostate cancer or heart disease. In their report published in the New England Journal of Medicine, the authors conclude: “We reviewed decades of research and found no compelling evidence that testosterone replacement therapy increases the incidence of prostate cancer or cardiovascular disease.”

—Edward R. Rosick, DO, MPH, MS


* Synder PJ. Hypogonadism in elderly men— what to do until the evidence comes. N Engl J Med. 2004 Jan 29;350(5):440-2.