Topic of the Month

Micronutrients and the nervous system

August 1, 2011

The metabolic functions of the brain and nervous system depend not only on the supply of macronutrients – carbohydrates, fats and proteins – but also on the availability of micronutrients.

file

Vitamins, carotenoids and essential fatty acids, as well as minerals and trace elements play a crucial role, particularly in the development of the nervous system at the start of life and during the aging process. Adequate availability of micronutrients is an essential and indispensible precondition for a well-functioning nervous system, and mental and emotional well-being in humans.

file

Nervous system and micronutrient functions

The nervous system is composed of the brain and spinal cord (the central nervous system, or CNS) plus the peripheral nervous system (PNS), which includes all nerves leaving the CNS. The nervous system forms a network of several billions of cells, the neurons, which may be connected to each other by protrusions called axons and dendrites. Motor neurons receive command signals from the brain and transmit these “orders” to the target organ –muscle. Sensory neurons are activated by stimuli from the environment (such as smells or tastes) and transmit information to the brain and spinal cord. There are also twelve pairs of cranial nerves which emerge directly from the brainstem. These belong to the PNS. They are connected to the muscles and the head’s sensory organs (e.g. eyes, nose and mouth). The PNS is divided into two functional areas: The somatic (or voluntary) nervous system controls all the muscle movements that are under conscious control; the other part, the autonomic (visceral or involuntary) nervous system, controls various activities of the body that are not subject to conscious control via nerves and hormones. These activities include blood pressure regulation, breathing, cell regeneration, heartbeat, digestion, body temperature and metabolism. The control centers of the autonomic nervous system are located in the ganglia (encapsulated collections of nerve cells) found along the spinal column, along the intestine, in the spinal cord, and in the brain. The knowledge necessary for the smooth functioning of the body is stored here. Three nervous systems form the true core of the autonomic nervous system, and they are often equated with it. These are the sympathetic, parasympathetic and enteric nervous systems. The enteric system controls the gastrointestinal system and is sometimes called the “second brain”. Put simply, the sympathetic and parasympathetic divisions are in opposition to each other. While the former prepares the body for action (fight or flight), the parasympathetic division is responsible for relaxing and regenerating the body (rest and digest). Most of the internal organs (e.g. heart, gastrointestinal tract, eyes) are therefore subject to two controls: one acts as the body’s accelerator, the other as the brake. The enteric system is autonomic in the true sense of the word, because in contrast to the sympathetic and parasympathetic systems it is not connected to the CNS. The nerves in the “second brain” have many tasks, such as coordination of intestinal motility, regulation of the immune system and control of fluid and nutrient uptake.

The B vitamins play a key role in the proper functioning of processes in the nerves and brain. Vitamin B1 is required for the provision of energy (glucose) to nerve cells and is involved in the transmission of nervous stimuli (1). The European Food Safety Authority (EFSA) recently confirmed that an adequate supply of vitamin B1 is essential to normal neurological development and function in infants and children up to the age of three years. Vitamin B6 is indispensible for amino acid metabolism and thus for synthesis of the neurotransmitters dopamine, GABA, and in particular serotonin. It is also required for the provision of energy to the nerve cells; sufficient glucose can only be synthesized from proteins and carbohydrates with the aid of vitamin B6. In addition, vitamin B6 is involved in the production of the “myelin sheaths”, the fats that enclose nerve fibers (axons). Vitamin B12 also plays an important part in synthesis of the myelin sheaths. Moreover, it is involved in DNA synthesis and thus in cell division. The concentration of vitamin B12 influences the effectiveness of folic acid (vitamin B9), which is of major significance for the metabolism of myelin components and of neurotransmitters. Like omega-3 fatty acids, folic acid is thought to be of great importance in the development of the nervous system at the start of life.

Minerals, too, influence processes in the nervous system; magnesium and calcium can modulate the transmission of nervous stimuli. The antioxidant trace elements zinc and selenium can probably reduce nerve-damage. Zinc also appears to be involved in the effectiveness of the neurotransmitter GABA (1).

Disease risk reduction

Diseases of the nervous system include strokedementia, multiple sclerosis, Parkinson’s disease and epilepsy. According to health reports from the World Health Organization (WHO), these major diseases are responsible for around twelve percent of deaths worldwide and are on the increase, especially in Western industrialized countries. They pose major challenges for health systems (2). But accidents, alcohol abuse and diabetes can also cause neurological damage which can lead to the malfunction or even total loss of function of organs. Prevention is crucial in the fight against the rising incidence of neurological disorders and nerve damage. The following outlines examples of disorders of the nervous system whose risk can be reduced by an adequate intake of micronutrients.

file

Multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system for which there is, as yet, no cure. It affects more women than men. With MS the immune system attacks the body’s own fatty tissue substance, myelin, which insulates nerve cells and aids transmission of impulses. It is not known what causes this autoimmune disease. There are epidemiologicalindications that it may be influenced by genetic and environmental factors such as smoking, by the Epstein-Barr virus, and by geographic latitude, i.e. it is less common near the equator and more frequent at higher northern and southern latitudes (3, 4). The incidence of MS also appears to diminish with a seasonal increase in the number of hours of sunshine (5, 6). A protective effect of greater vitamin D production from increased sunlight has been proposed (5, 7–9). Moreover, a link has been found between the amount of vitamin D available through exposure to the sun or from the diet (cod liver oil) in childhood and early adolescence and the time of onset of MS symptoms, and this strongly indicates that vitamin D could be a possible modulator of disease progression (10).

In other studies, MS patients were found to have inadequate blood levels of vitamin D. The results of some research into the treatment of MS patients appear to indicate that dietary supplementation with vitamin D could improve their symptoms. However, more studies are needed to substantiate this (11). There are other studies that offer evidence of a protective effect of vitamin D against MS: one investigation showed that women who consumed more than 400 IU vitamin D daily had a 40 percent lower risk of developing MS compared to wom-en who did not (12). Another study involving seven million employees of the US military showed that the risk of developing MS diminished with rising concentrations of 25-hydroxy vitamin D in the blood (13). Epidemiological research into the question of whether inadequate blood levels of vitamin D could be a risk factor for MS confirm this finding (11, 14).

Immunological findings in MS patients have established that vitamin D significantly influences regulatory T lymphocyte cells which can control T helper cells in the immune system. It appears that faulty T cells aggressively attack the body’s own myelin instead of fulfilling their true task of fighting microbes in the organism (3, 11).

Oxidative stress, which can damage myelin, appears to play a significant role in the pathogenesis of MS. Researchers point out that a sufficient supply of antioxidants in the diet is an important preventive factor (15, 16). With the exception of vitamin D, the role of micronutrients in the prevention and treatment of MS has hardly been investigated. There are early indications of a possible protective effect from omega-3 fatty acids (17). Other studies showed that MS patients had low vitamin E status and increased serum levels of homocysteine (18).

file

Parkinson’s disease

The Parkinson’s syndrome is one of the commonest diseases of the central nervous system. Over five million people worldwide are affected, and the numbers are rising (19). As with many neurological diseases, here too, inflammatory processes play an important role in pathogenesis. The diversity of signs and symptoms makes Parkinson’s disease very difficult to treat and until now the disease is incurable and its progression inexorable. Hence preventive measures are crucially important for maintaining health. A Finnish cohort follow-up study with 3,173 men and women aged between 50 and 79 provides evidence that high blood concentrations of vitamin D could reduce the risk of developing Parkinson’s disease by over 60 percent (20). Vitamin D and the vitamin D receptor gene have been discussed as possible environmental and genetic factors for neurological diseases like Parkinson‘s (21). Results from other studies show that patients in the early stages of Parkinson’s disease have distinctly lower vitamin D levels (22).

Another focus of research into Parkinson’s disease is the B vitamin complex: A Japanese case-control study found that low levels of vitamin B6 were associated with a high risk for this disease (23). In one study Brazilian scientists recommend giving Parkinson’s patients folic acid to lower the raised homocysteine levels brought about by conventional Parkinson’s medication with levo-dopa (24).

file

Dementia and depression

According to the World Alzheimer Report 2010 there are around 36 million dementia sufferers worldwide, whose care and treatment costs over 600 billion dollars per year. The number of sufferers is set to rise to 65.7 million by 2030 and to 115.4 million by 2050, primarily due to the growing proportion of over 65-year-olds in the world’s population. Currently, around two-thirds of global dementia cases and their associated costs affect Western industrialized countries, but the proportion of developing countries affected is growing constantly. As yet, only a few of the factors involved in the pathogenesis of this socially highly burdensome dis-ease are known, and since there is no prospect of a cure at present, research is primarily concerned with its prevention.

The term dementia includes neurocognitive disorders with a number of subtypes, such as Alzheimer’s disease, the most common form, and vascular dementia. An essential characteristic of dementia is the loss of neurons and their contact points (the synapses) in specific regions of the brain. It is thought that oxidative stress could be a deciding factor in the pathogenesis of Alzheimer’s disease (25).

Nutrition is an essential determinant of mental performance. Especially during the aging process, nutrients can partially prevent or at least delay an age-related decline in cognitive abilities. Vitamin D is under discussion as a particularly promising micronutrient, because of its influence on the nerves and neuroprotective properties (26). Various studies, including a cross-sectional study of older African-Americans (27), have revealed a correlation between a decline in bone density, accompanied by markedly lower levels of 25-hydroxy-vitamin D, and impaired cognitive performance. Other researchers specifically investigated whether an adequate supply of vitamin D reduces the risk of developing dementia: An Italian study of 69 men and women aged between 70 and 89 years living independently showed that cognitive performance was significantly impaired in those with a low intake of vitamin D (28). A large French study of over 5,500 older women also revealed that a lower intake of vitamin D in the diet is associated with impaired cognitive performance (29). In another study, with 1,766 English men and women over the age of 65, the researchers concluded that there was evidence that a lower serum 25-hydroxy vitamin D concentration is associated with increased odds of cognitive impairment among the older population. Serum 25-hydroxy vitamin D could therefore play an important role in the expression of neurotrophic factors (30). Further research is necessary to investigate whether vitamin D supplementation is a cost-effective and safe way of reducing the incidence of cognitive impairment in the elderly.

Beta-amyloid plaque deposits in the brain are associated with an increase in cell damage and cell death from oxidative stress. This can lead to loss of cognitive functions and increased risk of Alzheimer’s disease. A study of 5,395 participants over 55 years showed that those whose average daily intake of vitamin E was 18.5 milligrams had a 25 percent lower risk of developing dementia compared to participants whose daily dietary intake of vitamin E only averaged 9 milligrams (31). The researchers concluded that vitamin E, a potent fat-soluble antioxidant, could help prevent the onset of dementia.

Studies have shown that vitamin B12 could delay the onset of dementia (1). There is even evidence that changes in blood vitamin B12 concentrations could provide an indication of increased risk of developing dementia before its occurrence. An adequate intakecan improve the speech and cognitive abilities of older people. Conversely, adults with only marginal blood concentrations of vitamin B12 can exhibit impairment of these abilities. In the RANCHO-BERNARDO STUDY American scientists discovered that a good supply of the long-chain omega-3 fatty acid docosahexaenoic acid (DHA) can clearly provide protection against dementia (32).

Studies on the influence of micronutrients on depression provide evidence that targeted consumption of B-complex vitamins can improve the mood of older people suffering from incident depression (33). The same effect could be demonstrated for vitamin C, higher concentrations of which are found in the nerve endings than in any other organ (34). Long-chain polyunsaturated omega-3 fatty acids could also help alleviate symptoms of depression in older people, according to one Italian study (35). 

file

Sensory nerve functions, pain

Numerous studies have shown that an adequate intake of antioxidant micronutrients such as vitamin C and carotenoids (beta-caroteneluteinlycopene) is necessary for normal visual function (see also: Micronutrients for healthy aging). Age-related macular degeneration is the most common cause of blindness in Western industrialized countries. Macular pigment is composed of lutein and zeaxanthin. Moreover, the nerve cells in the retina contain a lot of omega-3 fatty acids. Studies have shown that an adequate intake of these micronutrients has a positive influence on the maintenance of visual acuity in old age (36, 37).  Long-chain omega-3 fatty acids and folic acid appear to be important for auditory nerve function (38–40).

As regards sensitivity to pain, several studies – in particular relating to premenstrual syndrome (PMS) in women – demonstrated that pain relief could be achieved by targeted administration of single B-complex vitamins or combinations of them (41).

References

  1. Bourre J.M.  Effects of Micronutrients (in Food) on the Structure and Function of the Nervous System: Update on Dietary Requirements for Brain. Part 1: Micronutrients. J Nutr Health Aging. 2006; 10(5):377–385.
  2. Neurological Disorders: Public Health Challenges. World Health Organization 2006.
  3. Pierrot-Deseilligny C. Clinical implications of a possible role of vitamin D in multiple sclerosis. J Neurol. 2009; 256(9):1468–1479.
  4. Martyn C.N. McAlpine's Multiple Sclerosis. 2. WB Matthews ed. Edinburgh London Melbourne and New York: Churchill Livingstone; 1991. The epidemiology of multiple sclerosis.
  5. Gale C.R., Martyn CN. Migrant studies in multiple sclerosis. Prog Neurobiol. 1995; 47:425–448.
  6. Acheson E.D. et al. Some comments on the relationship of the distribution of multiple sclerosis to latitude, solar radiation and other variables. Acta Psychiatr Scand. 1960; 35:132–147.
  7. Norman J.E. et al. Epidemiology of multiple sclerosis in US veterans: 2. Latitude, climate and the risk of multiple sclerosis. J Chronic Dis. 1983; 36:551–559.
  8. Goldberg P. Multiple sclerosis: vitamin D and calcium as environmental determinants of prevalence (a viewpoint). Part 1: sunlight, dietary factors and epidemiology. Int J Environ Studies. 1974; 6:19–27.
  9. McDowell T.Y. et al. Sun exposure, vitamin D and age at disease onset in relapsing multiple sclerosis. Neuroepidemiology. 2011; 36(1):39–45.
  10. Sutherland J.M. et al. The prevalence of multiple sclerosis in Australia. Brain. 1962; 85:146–164.
  11. Zhang R., Naughton D.P. Vitamin D in health and disease: Current perspectives. Nutr J. 2010; 9: 65.
  12. Munger K.L. et al. Vitamin D intake and incidence of multiple sclerosis. Neurology. 2004; 62: 60–65.
  13. Munger K.L. et al. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006; 296:2832–2838.
  14. Pierrot-Deseilligny C, Souberbielle J.C. Is hypovitaminosis D one of the environmental risk factors for multiple sclerosis? Brain. 2010; 133(7):1869–1888.
  15. Hadžović-Džuvo A. et al. Serum total antioxidant capacity in patients with multiple sclerosis. Bosn J Basic Med Sci. 2011; 11(1):33–36.
  16. Miller E. et al. Oxidative stress in multiple sclerosis. Pol Merkur Lekarski. 2009; 27(162):499–502.
  17. Yadav V et al. Complementary and alternative medicine for the treatment of multiple sclerosis. Expert Rev Clin Immunol. 2010; 6(3):381–395.
  18. Salemi G. et al. Blood lipids, homocysteine, stress factors, and vitamins in clinically stable multiple sclerosis patients. Lipids Health Dis. 2010 18; 9:19.
  19. www.parkinson-world.com
  20. Knekt P. et al. Serum Vitamin D and the Risk of Parkinson Disease. Arch Neurol. 2010; 67(7):808–811.
  21. Butler M.W. et al. Vitamin D receptor gene as a candidate gene for Parkinson disease. Ann Hum Genet. 2011; 75(2):201–210.
  22. Evatt M.L.et al. High prevalence of hypovitaminosis D status in patients with early Parkinson disease. Arch Neurol. 2011; 68(3):314 –319.
  23. Murakami R. et al. Dietary intake of folate, vitamin B6, vitamin B12 and riboflavin and risk of Parkinson's disease: a case-control study in Japan. Br J Nutr. 2010;104(5):757–764.
  24. dos Santos E.F. et al. Evidence that folic acid deficiency is a major determinant of hyper-homocysteinemia in Parkinson's disease. Metab Brain Dis. 2009; 24(2):257–269.
  25. Butterfield DA, Perluigi M, Sultana R. Oxidative stress in Alzheimer's disease brain: new insights from redox proteomics. Eur J Pharmacol. 2006; 545(1):39–50.
  26. Annweiler C. et al. Vitamin D and ageing: neurological issues. Neuropsychobiology 2010; 62:139–150.
  27. Wilkins C.H. et al. Vitamin D deficiency is associated with worse cognitive performance and lower bone density in older African Americans. J Natl Med Assoc. 2009; 101(4): 349– 354.
  28. Rondanelli M, et al. Relationship among nutritional status, pro / antioxidant balance and cognitive performance in a group of free-living healthy elderly. Minerva Med. 2007; 98(6):639–645.
  29. Annweiler C. et al. Dietary intake of vitamin D and cognition in older women: a large population-based study. Neurology. 2010; 75(20):1810 –1816.
  30. Llewellyn D.J. et al. Serum 25-hydroxyvitamin D concentration and cognitive impairment. J Geriatr Psychiatry Neurol. 2009; 22(3):188–195.
  31. Devore E.E. et al. Dietary antioxidants and long-term risk of dementia. Arch Neurol. 2010; 67(7):819–825.
  32. Lopez L.B. et al.: High Dietary and Plasma Levels of the Omega-3 Fatty Acid Docosa-hexaenoic Acid Are Associated with Decreased Dementia Risk: THE RANCHO BERNARDO STUDY; The Journal of Nutrition, Health & Aging 2011; 15(1):25–3.
  33. Skarupski K.A. et al.  Longitudinal association of vitamin B-6, folate, and vitamin B-12 with depressive symptoms among older adults over time. Am J Clin Nutr. 2010; 92(2): 330–335.
  34. Zhang M, et al. Vitamin C provision improves mood in acutely hospitalized patients. Nutrition. 2011; 27(5):530– 533.
  35. Rondanelli M. et al.  Long-chain omega-3 polyunsaturated fatty acids supplementation in the treatment of elderly depression: Effects on depressive symptoms, on phospholipids fatty acids profile and on health-related quality of life. J Nutr Health Aging. 2011; 15(1):37–44.
  36. Olmedilla B. et al. Lutein in patients with cataracts and age-related macular degeneration: a long-term supplementation study. J Sci Food Agric. 2001; 81(9):904–909.
  37. Sangiovanni JP et al. Omega-3 Long-chain polyunsaturated fatty acid intake and 12-y incidence of neovascular age-related macular degeneration and central geographic atrophy: AREDS report 30, a prospective cohort study from the Age-Related Eye Disease Study. Am J Clin Nutr. 2009; 90(6):1601–1607.
  38. Gopinath B. et al. Consumption of omega-3 fatty acids and fish and risk of age-related hearing loss. Am J Clin Nutr. 2010; 92:416–421.
  39. Shargorodsky J. et al. Vitamin Intake and Risk of Hearing Loss in Men. American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF) Annual Meeting 2009.
  40. Gopinath B. et al: Serum Homocysteine and Folate Concentrations Are Associated with Prevalent Age-Related Hearing Loss. J Nutr. 2010; 140(8):1469–1474.
  41. Chocano-Bedoya P.O. et al.  Dietary B vitamin intake and incident premenstrual syn-drome. Am J Clin Nutr. 2011; 93(5):1080–1086.