Hormone precursors, vitamins and minerals can also help keep the brain healthy by staving off mood problems and memory loss.

Seeds from Griffonia simplicifolia, an African shrub, contain a high level of 5-hydroxytryptophan (5-HTP), which helps the brain build serotonin, so the herb has been formulated in brain health products. Serotonin is an important hormone that affects sleep, appetite and mood. A 1998 review noted therapeutic administration of 5-HTP has been shown to be effective in treating brain ailments such as depression, binge eating and insomnia.¹ And a 1997 review noted 5-HTP possesses anti-depressive properties.²

Another hormone, melatonin also plays a role in sleep and general brain health. A University of South Alabama, Mobile, study from 2001 found melatonin inhibited the process of forming amyloid-beta peptides in animal and human cell cultures.³ A University of California, San Diego, study showed 6 mg of melatonin, administered two hours before bedtime, enhanced sleep, memory and mood in the elderly.⁴

And melatonin also improved sleep efficiency in patients with schizophrenia in a 2000 study from Tel Aviv University, Israel.⁵ In the randomized, double blind, crossover trial, patients with schizophrenia who added 2 g/d of melatonin to their normal treatment significantly improved rest-derived sleep efficiency compared with placebo.

Vitamin intellect

Vitamin E includes eight natural compounds (four tocopherols and four tocotrienols) that possess neuroprotective activity; however, alpha-tocotrienol has the most cognitive research of all the vitamin E components. Professor Chandan Sen of the Ohio State University Medical Center and his research team found a low concentration of alpha-tocotrienol, but not alpha-tocopherol, prevented glutamate-induced brain cell death, a physiological phenomenon that occurs in the brain during a stroke.⁶

Several follow up Ohio State University studies found alpha-tocotrienol acts on key molecular checkpoints to protect against glutamate- and stroke-induced neurodegeneration in rats.^7,8 The researchers then moved on to dog studies, finding oral supplementation with tocotrienols (as Tocomin SupraBio® from Carotech) reduced overall brain tissue damage, prevented loss of neural connections and helped sustain blood flow in the brains of dogs that had strokes.⁹ The researches found 24 hours after a stroke, lesions indicating brain tissue damage were about 80% smaller in dogs that received tocotrienol supplementation than were the lesions in dogs that received no intervention. Furthermore, tocotrienols prevented loss of white matter fiber tract connectivity after stroke. Imaging tests showed the treated animals brains had better blood flow at the stroke site as compared to untreated dogs brains, a difference attributed to tiny collateral blood vessels ability to improve circulation in the brain when blood flow stopped in more substantial vessels.

Turning to human patients, researchers noted elderly subjects (aged 80 years or older) with the highest plasma levels of total tocopherols, total tocotrienols or total vitamin E had a reduced risk of developing Alzheimer's disease in comparison to subjects who had the least.¹⁰ The same group of researchers also conducted another study that found low plasma tocopherol and tocotrienol levels were associated with increased odds of mild cognitive impairment and Alzheimer's disease.¹¹

A recently completed, but not published, randomized, double blind, placebo-controlled clinical trial found humans with white matter lesions who took the supplement Tocovid SupraBio from Hovid Ltd. (which contains Tocomin SupraBio) had smaller lesions after two years. White matter lesions are subclinical brain damage associated with an increased risk of stroke. And the Ohio State University researchers are at it once again, currently working on another human clinical trial on neuroprotection. The NUTRITION" Trial (Natural Tocotrienol Against Ischemic Stroke Event) aims to study the potential of Tocomin SupraBio in reducing the risk for stroke.

Vitamin D has been recognized by the Institute of Medicine (IOM) as having bone health benefits, but the sunshine vitamin has received recent praise for its positive effects on brains. A May 2012 study found vitamin D deficiency is prevalent in adolescents with severe mental illness.¹² Vitamin D deficiency (25-hydroxy-vitamin D [25-OH-D] levels less than 20 ng/ml) was present in 34% of the 104 adolescents with acute mental health issues, and vitamin D insufficiency (25-OH D levels from 20 to 30 ng/ml) was present in 38%. A remaining 28% were in the normal range. Adolescents with psychotic features had lower vitamin D levels (20.4 ng/ml vs. 24.7 ng/ml). The association for vitamin D deficiency and psychotic features was substantial.

A January 2012 study found low vitamin D levels were associated with depressive symptoms, especially in people with a history of depression.¹³ And correcting a vitamin D deficiency can reduce depression, according to a study presented in June 2012 at The Endocrine Societys 94th Annual Meeting. Vitamin D supplementation reduced depression symptoms in women with moderate to severe depression. The women were deficient in vitamin D before treatment, and they did not change their antidepressant medications or other environmental factors related to depression.

A September 2012 study reported pregnant women who are deficient in vitamin D are more likely to give birth to children with slower brain development, and decreased mental and motor skills.¹⁴ A positive linear relationship was found between circulating concentrations of maternal 25(OH)D3 concentrations during pregnancy, and mental and psychomotor scores in the offspring. After adjustment for potential confounders, infants of mothers with 25(OH)D3 concentrations during pregnancy more than 30 ng/mL showed higher mental score and higher psychomotor score compared with those of mothers with 25(OH)D3 concentrations less than 20 ng/mL.

Better known for their energy prowess, B vitamins can also improve brain power because they are vital for the synthesis of neurotransmitters, such as serotonin. A January 2012 study found daily supplementation with folic acid and vitamin B12 improved cognitive functioning, particularly in immediate and delayed memory performance.¹⁵ Researchers found 400 mcg/d of folic acid plus 100 mcg/d vitamin B12 for two years helped prevent cognitive decline in older adults with elevated psychological distress.

A September 2012 cross-sectional analysis of the West Australian Pregnancy Cohort (Raine) Study found adolescents with a lower intake of vitamins B1, B2, B3, B5, B6 and folate had higher aggressive and delinquent behavior.¹⁶ Reduced intake of vitamin B6 and folate was also associated with higher withdrawn and depressed behavior.

Mindful minerals

Magnesium can factor in Alzheimer's disease. A November 2011 University of Palermo, Italy, study found serum ionized magnesium levels are altered in patients with mild to moderate Alzheimers disease, and these levels directly relate to cognitive function in these patients. Blood tests revealed magnesium was significantly lower in the Alzheimer's disease group as compared to a group of age-matched control adults without the disease.¹⁷

Data from a 2011 study from Tsinghua University, Beijing, suggested increasing magnesium levels with supplementation of Magtein (from AIDP) in the brain increased synaptic plasticity, meaning brain cells are better able to respond to signals.¹⁸ Plus, the researchers noted enhancement of plasticity in certain brain regions may enhance the efficacy of cognitive therapy for anxiety disorders. Researchers from Massachusetts Institute of Technology (MIT), Cambridge, released data in 2010 that suggested increasing brain magnesium levels with Magtein supplementation led to enhanced learning abilities, working memory and short- and long-term memory in rats. Pattern completion ability was also improved in aged rats.¹⁹

The mineral zinc can also predict depression. A February 2012 study from the New England Research Institutes noted low dietary or supplemental zinc intake was linked to depressive symptoms in women.²⁰ Researchers used cross-sectional data from the population-based Boston Area Community Health survey (2002 to 2005), which included dietary and supplement use data from food frequency questionnaires. Zinc was associated with depressive symptoms in women (n=2,163), but not men (n=1,545), and women with low dietary or supplemental zinc intake were more likely to have depressive symptoms. Associations were stronger among women using antidepressant medications.

Providing supplemental chromium picolinate to elderly adults with early memory decline improved cognitive performance and brain function, according to a 2010 study.²¹ Researchers from the University of Cincinnati College of Medicine randomized 26 older adults with indications of early memory decline in the double blind, placebo-controlled study to receive 1,000 mcg chromium picolinate (as Chromax®, from Nutrition 21) or placebo capsules for 12 weeks. Chromium supplementation improved learning, recall and recognition memory tasks.

From EFAs to botanicals, vitamin, hormone precursors and minerals, natural ingredients can be included in foods, beverages and supplements that help brain health at every stage in life.

Find more information on brain health in the Natural Products Insider Cognitive health library.

References

1. Birdsall TC." 5-Hydroxytryptophan: a clinically-effective serotonin precursor." Altern Med Rev. 1998 Aug;3(4):271-80.

2. Byerley WF et al. "5-Hydroxytryptophan: a review of its antidepressant efficacy and adverse effects." J Clin Psychopharmacol. 1987 Jun;7(3):127-37.

3. Poeggeler B et al. "Melatonin reverses the profibrillogenic activity of apolipoprotein E4 on the Alzheimer amyloid Abeta peptide." Biochemistry. 2001 Dec 11;40(49):14995-5001.

4. Jean-Louis G, von Gizycki H, Zizi F. " Melatonin effects on sleep, mood, and cognition in elderly with mild cognitive impairment." J Pineal Res. 1998 Oct;25(3):177-83.

5. Shamir E et al. "Melatonin improves sleep quality of patients with chronic schizophrenia." J Clin Psychiatry. 2000 May;61(5):373-7.

6. Sen CK et al. " Molecular basis of vitamin E action. Tocotrienol potently inhibits glutamate-induced pp60(c-Src) kinase activation and death of HT4 neuronal cells." J Biol Chem. 2000 Apr 28;275(17):13049-55.

7. Khanna S et al. "Neuroprotective properties of the natural vitamin E alpha-tocotrienol." Stroke. 2005 Oct;36(10):2258-64.

8. Khanna S, et al. "Nanomolar vitamin E alpha-tocotrienol inhibits glutamate-induced activation of phospholipase A2 and causes neuroprotection." Journal of Neurochemicstry 112 (2010): 1248-1260.

9. Rink C et al, "Tocotrienol vitamin E protects against preclinical canine ischemic stroke by inducing arteriogenesis." J Cereb Blood Flow Metab. 2011 Nov;31(11):2218-30. doi: 10.1038/jcbfm.2011.85.

10. Mangialasche F et al. " High plasma levels of vitamin E forms and reduced Alzheimer's disease risk in advanced age." J Alzheimers Dis. 2010;20(4):1029-37.

11. Mangialasche F et al. " Tocopherols and tocotrienols plasma levels are associated with cognitive impairment." Neurobiol Aging. 2012 Oct;33(10):2282-90.

12. Gracious BL et al. "Vitamin D deficiency and psychotic features in mentally ill adolescents: A cross-sectional study." BMC Psychiatry. 2012 May 9;12:38.

13. Hoang MT et al. " Association between low serum 25-hydroxyvitamin D and depression in a large sample of healthy adults: the Cooper Center longitudinal study." Mayo Clin Proc. 2011 Nov;86(11):1050-5.

14. Morales, E. " Circulating 25-Hydroxyvitamin D3 in Pregnancy and Infant Neuropsychological Development." DOI: 10.1542/peds.2011-3289

15. Walker JG et al. " Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms--the Beyond Ageing Project: a randomized controlled trial." Am J Clin Nutr. 2012 Jan;95(1):194-203.

16. Herbison, C et al "Low intake of B-vitamins is associated with poor adolescent mental health and behavior." Preventive Medicine. online Sept. 23, 2012. DOI 10.1016/j.bbr.2011.03.031

17. Barbagallo M et al. " Altered ionized magnesium levels in mild-to-moderate Alzheimer's disease." Magnes Res. 2011 Sep;24(3):S115-21.

18. Abumaria N et al. " Effects of elevation of brain magnesium on fear conditioning, fear extinction, and synaptic plasticity in the infralimbic prefrontal cortex and lateral amygdala." J Neurosci. 2011 Oct 19;31(42):14871-81.

19. Maserejian NN, Hall SA, McKinlay JB. "Low dietary or supplemental zinc is associated with depression symptoms among women, but not men, in a population-based epidemiological survey." J Affect Disord. 2012 Feb;136(3):781-8.

20. Slutsky I et al. " Enhancement of learning and memory by elevating brain magnesium." Neuron. 2010 Jan 28;65(2):165-77.

21. Krikorian R et al. "Improved cognitive-cerebral function in older adults with chromium supplementation." Nutr Neurosci. 2010 Jun;13(3):116-22.