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HOPES: Huntington's Outreach Project for Education, at Stanford

Diet and Neurogenesis

A novel track of research has unearthed new meaning to the old adage “you are what you eat”. Research suggests that our diet plays a role in neurogenesis, the process by which we produce new neurons. Therefore, a diet rich in “brain food” may promote neurogenesis and thereby might repair some of the damage brought on by Huntington’s disease (HD).

Neurogenesis and HD^

The old myth that a person is born with as many neurons as he would ever have has recently been overturned. Though neurogenesis is most abundant before birth, scientists have shown that adults can make new neurons throughout life. This allows our brains to age gracefully, as these new neurons work to replace the neurons that inevitably die. Neurogenesis allows us to have flexible brains throughout life, which is critical for learning new skills (Greenwood and Parasuraman, 2010). For more information on neurogenesis, click here.

In particular, neurogenesis is important in the context of HD. Neurogenesis continues to occur in HD patients and, in fact, increases as the disease progresses. This increase is thought to be the brain’s attempt to repair itself in response to the widespread neuronal death caused by the disease. However, neurogenesis does not happen fast enough to counter the damage incurred (Taupin, 2008).

It is possible that a diet that promotes neurogenesis could help counter some of the deficits experienced by HD patients. Some scientists have explored how diet can impact neurogenesis, and have found a number of nutrients and dietary regimes that may play a role.

Dietary Restriction^

One major track of research on diet and neurogenesis focused on dietary restriction (DR). DR is a strategy wherein calories are limited to about 70% of the normal diet (Levenson and Rich, 2007). This calorie reduction has been shown to lengthen lifespan; the lives of rats and mice can be extended by as much as 50% if they are put on a restricted diet at a young age, and maintain that diet throughout life. In rats and monkeys, DR helps protect against age-related diseases, like cancer, diabetes, and cardiovascular disease (Mattson et al., 2004)

Scientists think DR brings about these beneficial effects by conditioning cells to be better at protecting themselves. DR is a mild stress that puts cells on the defensive, and causes them to start expressing protective genes and stockpiling useful proteins. Therefore, cells stressed by DR are better able to cope with further stressors. For more information on DR, click here.

One stressor that occurs in many neurodegenerative conditions, like Alzheimer’s, Parkinson’s, and HD, and can be ameliorated by DR, is oxidative stress. In HD, oxidative damage occurs when injured neurons release free radicals, which go on to damage neurons around them (Mattson et al., 2004). For more information on oxidative damage, click here. Therefore, DR may help patients with neurodegenerative diseases by causing neurons to fortify themselves, which could prepare them for the stress caused by HD.

Scientists also believe that DR can help patients with neurodegenerative conditions by promoting neurogenesis. DR increases adult neurogenesis in young adult rats, and reduces age-related declines in neurogenesis in older mice (Levenson and Rich, 2007). Furthermore, DR stimulates neurogenesis in the hippocampus, a brain region important for memory. DR also causes an increase in levels of BDNF, a protein shown to help newly born neurons survive (Mattson et al., 2004). For more information on BDNF, click here. Researchers have found that DR can improve the symptoms of HD and several other neurodegenerative conditions in mice. When rats were injected with a chemical that causes brain damage, the rats kept on a restricted diet were more resistant to the chemical’s neurodegenerative effects, and showed fewer learning and memory problems (Mattson et al., 2004). When HD mice were kept on a restricted diet, they showed less striatal neuron death, it took longer for movement problems to arise, and the mice lived longer (Mattson et al, 2004). So DR may protect against neurodegenerative conditions by stimulating neurogenesis and causing neurons to fortify themselves.

DR, however, is a drastic strategy: it takes tremendous willpower to limit calories to 70% of the normal diet. Furthermore, DR is difficult to implement properly; there is a risk of starvation if the diet is unbalanced, which can have wide-ranging consequences. Luckily, similar effects to DR have been found in mice by simply increasing the amount of time between meals (Stangl and Thuret, 2009).

Some scientists have attempted to harness the beneficial effects of DR through resveratrol, a chemical found in red wine. Resveratrol mimics many of the effects of DR, and is thought to work through the same biological pathways (Greenwood and Parasuraman, 2010). For more information, click here.

So DR and resveratrol may promote neurogenesis, and in this way might protect against the brain damage found in HD.

Dangers of a High-Fat Diet^

Conversely, researchers have also studied situations where cells have too many calories, and have found that neurogenesis is impaired. Mice on a high-fat diet have lower levels of BDNF in the hippocampus, and decreased neurogenesis in a particular area of the hippocampus called the dentate gyrus (Park et al., 2010). Furthermore, when injected with a chemical that injures the brain, mice fed a high-fat diet experienced much more damage than those fed a normal diet. Diets high in fat also decrease the learning and cognitive capabilities of rats (Greenwood and Prasuraman, 2010). Thus, experiments on rodents consistently show that a high-fat diet is unhealthy for the brain.

Vitamins, Nutrients, and Foods that promote Neurogenesis^

Another line of research on diet and neurogenesis has investigated the effect of dietary nutrients on the birth of new neurons. Several antioxidants, such as flavonoids, vitamin E, and curcumin, increase neurogenesis in rodent brains. Antioxidants are chemicals that prevent damage from free radicals, and thus might promote neurogenesis by protecting new neurons, among other things (Gómez-Pinilla, 2008). Flavonoids, found in cocoa and blueberries, are chemicals that increase neurogenesis in the hippocampus of stressed rats, possibly by increasing levels of BDNF (Stangl and Thuret, 2009), and/or by improving blood flow to the brain, which can increase hippocampal neurogenesis (Spencer, 2009). Vitamin E, abundant in vegetable oils, nuts, and green leafy vegetables, aids neurological performance in aging mice (Gómez-Pinilla, 2008). Curcumin, found in yellow curry spice, may increase neurogenesis in the hippocampus of rodents by activating certain cell signaling pathways known to increase neurogenesis and decrease stress responses (Stangl and Thuret, 2009). For more information on curcumin, click here.

Another antioxidant, found in green tea, goes one step further than the others. The chemical (-)-epigallocatechin-3-gallate (called EGCG) promotes neurogenesis in the hippocampus (Yoo et al., 2010), and has been shown to reduce the damage from oxidative stress in other neurodegenerative diseases (Ehrnhoefer et al., 2006). When flies with a form of HD were treated with EGCG, their control over their movements improved (Ehrnhoefer et al., 2006). EGCG might also directly fight the damage of HD, as it has been shown to slow the rate at which the mutant form of the huntingtin protein forms the plaques that are thought to hurt the brain (Ehrnhoefer et al., 2006).

In addition to antioxidants, other nutrients have also been shown to play a role in neurogenesis. Omega-3 fatty acids, present in fish and flaxseed, might also promote neurogenesis, and have been shown to decrease cognitive decline seen with aging and neurodegenerative diseases such as Alzheimer’s (Yurko-Mauro et al, 2010). For more information, click here. Vitamins might stimulate the birth of new neurons since, in some cases, vitamin deficiency can inhibit neurogenesis. For example, deficits in zinc inhibit neurogenesis in the hippocampus of rodents. Zinc, a vitamin essential for normal brain development, promotes the survival and proliferation of neural stem cells, which are the main cell type capable of generating neurons (Adamo and Oteiza, 2010). Therefore, zinc deficiency inhibits neurogenesis in the hippocampus of rodents. Similarly, a deficiency of retinoic acid, a metabolite of vitamin A found in animal foods such as milk, inhibits hippocampal neurogenesis (Stangl and Thuret, 2009).

Altogether, research on diet and neurogenesis is not conclusive. It is difficult to study nutrients effectively: studying a nutrient in isolation ignores many of the complex interactions the nutrient may have in the body. However, there are a few relatively consistent messages that emerge. A vitamin-rich, low-fat diet aids neurogenesis in experiments with rodents, and a low-calorie diet mitigates the effects of neurogenerative disease in mice. As for humans, this diet has not been shown to directly help neurogenesis or ameliorate the problems of HD (Huntington Study group, 2008; Block et al., 2011), but healthy diets have a vast number of other physical and mental benefits: longer life, elevated mood, and higher energy levels, to name a few. In conclusion, eating healthy might promote neurogenesis – but even if it does not, a healthy diet certainly will not hurt.

For Further Reading^

Adamo AM, Oteiza PI. Zinc deficiency and neurodevelopment: the case of neurons. Biofactors. 2010 Mar-Apr; 36 (2) :117-24

A technical paper that discusses the impact of zinc deficiency on the brain

Block RC, Dorsey ER, Beck CA, Brenna JT, Shoulson I. Altered cholesterol and fatty acid metabolism in Huntington disease. J Clin Lipidol. 2010 Jan-Feb;4(1):17-23. Review

A technical paper that discusses Omega-3 fatty acids and their effects on HD.

Curtis MA, Penney EB, Pearson AG, van Roon-Mom WM, Butterworth NJ, Dragunow M, Connor B, Faull RL. Increased cell proliferation and neurogenesis in the adult human Huntington’s disease brain. Proc Natl Acad Sci U S A. 2003 Jul 22; 100 (15) :9023-7.

A technical paper that discusses neurogenesis in an HD brain

Ehrnhoefer DE, Duennwald M, Markovic P, Wacker JL, Engemann S, Roark M, Legleiter J, Marsh JL, Thompson LM, Lindquist S, Muchowski PJ, Wanker EE. Green tea (-)-epigallocatechin-gallate modulates early events in huntingtin misfolding and reduces toxicity in Huntington’s disease models. Hum Mol Genet. 2006 Sep 15;15(18):2743-51. Epub 2006 Aug 7.

A technical paper that describes how EGCG, an antioxidant found in green tea, may change the way that the mutant huntingtin protein forms harmful plaques

Greenwood PM, Parasuraman R. Neuronal and cognitive plasticity: a neurocognitive framework for ameliorating cognitive aging. Front Aging Neurosci. 2010 Nov 29; 2:150.

A technical paper that discusses strategies to counter the neuron damage that accompanies aging, such as education, exercise, dietary restriction, and a low-fat diet, and goes into research that has been performed on rodents.

Gómez-Pinilla, F. Brain foods: the effects of nutrients on brain function. Nature Reviews Neuroscience. 2008 Jul. Review; 9:568-578.

A technical paper that discusses how various nutrients affect brain function.

Huntington Study Group TREND-HD Investigators. Randomized controlled trial of ethyl-eicosapentaenoic acid in Huntington disease: the TREND-HD study. Arch Neurol. 2008 Dec;65(12):1582-9.

Levenson CW, Rich NJ. Eat less, live longer? New insights into the role of caloric restriction in the brain. Nutr Rev. 2007 Sep; 65 (9) :412-5.

A paper that discusses the impact of caloric restriction on the brain in rodents

Park HR, Park M, Choi J, Park KY, Chung HY, Lee J. A high-fat diet impairs neurogenesis: involvement of lipid peroxidation and brain-derived neurotrophic factor. Neurosci Lett. 2010 Oct 4; 482 (3) :235-9.

A technical paper that discusses the impact of a high-fat diet on rodents

Mattson MP, Duan W, Wan R, Guo Z. Prophylactic activation of neuroprotective stress response pathways by dietary and behavioral manipulations. NeuroRx. 2004 Jan; 1 (1) :111-6.

A technical paper that discusses dietary restriction and its effect on the brain in rodents

Spencer JP. Beyond antioxidants: the cellular and molecular interactions of flavonoids and how these underpin their actions on the brain. Proc Nutr Soc. 2010 May; 69 (2) :244-60.

A technical paper that discusses the impact of flavonoids on the brain

Stangl D, Thuret S. Impact of diet on adult hippocampal neurogenesis. Genes Nutr. 2009 Dec; 4 (4) :271-82.

A technical paper that discusses the science behind various dietary strategies and nutrients that have an impact on neurogenesis in the adult hippocampus

Taupin P. Adult neurogenesis, neuroinflammation and therapeutic potential of adult neural stem cells. Int J Med Sci. 2008 Jun 5; 5 (3) :127-32.

A technical paper that discusses neurogenesis and neural stem cells

Yurko-Mauro K, McCarthy D, Rom D, Nelson EB, Ryan AS, Blackwell A, Salem N Jr, Stedman M; MIDAS Investigators. Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement. 2010 Nov;6(6):456-64.

A technical paper that discusses how Omega-3 fatty acids may aid patients with neurodegenerative conditions

Yoo KY, Choi JH, Hwang IK, Lee CH, Lee SO, Han SM, Shin HC, Kang IJ, Won MH. (-)-Epigallocatechin-3-gallate increases cell proliferation and neuroblasts in the subgranular zone of the dentate gyrus in adult mice. Phytother Res. 2010 Jul;24(7):1065-70.

A technical paper that discusses how EGCG enhances neurogenesis

M. Hedlin 6/17/2011