Today in the U.S., we are commonly instructed to lower our fat intake because word is out that fats are bad. Low-fat, non-fat, and even “fake fat” food products dominate supermarket shelves. Consumers typically fear fat in any form. However, not all fats are bad. In fact, some types of fats are actually necessary for life and health and should not be eliminated from the diet. This chapter examines the different types of fats, as well as the effect that these fats can have on the brain. In addition, this chapter reveals how optimizing the amount and type of fat in the diet may help combat Huntington´s disease (HD).
Saturated vs. Unsaturated Fat^
The whole of issue of fat in the diet has become very confusing, mainly because there are so many different types of fat. Essentially, there are two broad categories of fat: saturated fat and unsaturated fat. These two types of fat differ in their chemical structure. Saturated fatty acids (the building blocks of saturated fat) have no double bonds (a particular kind of chemical link between adjoining molecules) and this lack of double bonds means that there are no gaps in the fatty acid chain: it is packed with CH2 molecules. Unsaturated fatty acids (the building blocks of unsaturated fat), on the other hand, have double bonds and these double bonds break up the string of CH2´s and create gaps within the fatty acid chain. See figure 1 for a depiction of the difference between saturated and unsaturated fatty acids. We will explore how this difference in chemical structure affects how different types of fat interact with the body below.
Saturated fats (meats, butter, dairy products) are solid at room temperature, whereas unsaturated fats (vegetable oils) are liquid at room temperature. Due to their difference in chemical structure, saturated fats and unsaturated fats exert different effects within the body. Because saturated fatty acid chains have no gaps, they are able to pack together very tightly. When these tightly packed saturated fatty acids enter the bloodstream, they increase levels of “bad” cholesterol known as low-density lipoprotein (LDL) cholesterol and clog arteries. In comparison, unsaturated fats do not increase “bad” cholesterol and, in fact, are able to increase levels of “good” cholesterol known as high-density lipoprotein (HDL) cholesterol. HDL is able to grab LDL and escort it to the liver where it is broken down and eventually removed from the body. Thus, by increasing levels of HDL, unsaturated fats are able to protect against the damage done by saturated fats. Since heart disease is a leading cause of death for people with HD, it is especially important to keep the heart healthy and limit intake of saturated fat. (For more information on the many complications of HD, including heart disease, click here.) And as we will see below, there are even more reasons than heart disease for people with HD to be conscientious about the types of fat that they consume.
Because saturated fats were shown to be so unhealthy, food manufacturers decided to start using more unsaturated fats. The problem is that unsaturated fats spoil quickly. Food manufacturers solved this problem by putting unsaturated fats through the process of hydrogenation, which essentially alters the chemical structure of unsaturated fats and makes them more solid and long-lasting. However, when unsaturated fat is hydrogenated, a new fat called trans fat is produced. Fried foods, doughnuts, cookies, and crackers all contain high levels of trans fat. Trans fat rarely exists in nature and has been shown to be toxic to the body. Not only does it increase levels of “bad” cholesterol, it also decreases levels of “good” cholesterol. Thus, it has no redeeming qualities within the body and, as will be discussed later, it can worsen HD symptoms.
The relation between fat and nerve cells^
Nutrition is an integral component of our daily life routine and it has the potential to modulate brain health and function. Although it may at first seem strange, fat is essential for brain development and maintenance. In fact, about two-thirds of the brain is composed of fat, which may come as a surprising statistic. Where is all that fat? It is found in two places associated with nerve cells themselves. First, the protective covering of nerve cells called myelin is 70% fat. More importantly, the membranes of nerve cells are made of a thin double-layer of fatty acid molecules. After the body breaks down fat from the diet into fatty acids, the brain then uses these fatty acids by incorporating them into its cell membranes. Nerve cell membranes are extremely important because their composition determines what is able to pass into and out of the cell. Oxygen, glucose, and the nutrients that the cell needs to survive all must pass through the membrane and into the cell´s interior. When saturated fatty acids are incorporated into normally very fluid cell membranes, they pack very tightly because saturated fatty acid chains have no gaps. Thus, essential nutrients are unable to get into the cell, making the cell less healthy and more prone to injury. In contrast, unsaturated fats can be beneficial to nerve cells because they prevent the tight packing of fatty acids in the membrane. Unsaturated fatty acids have gaps in their chains and these gaps allow for a certain amount of “fluidity.”
Membrane fluidity is absolutely essential for the optimal function of most cells in the body, but it is especially important for nerve cells. In addition to letting in essential nutrients and keeping out harmful substances, nerve cell membranes also contain proteins that act as receptors for some neurotransmitters. Neurotransmitters are the chemical messengers that nerve cells use to communicate with each other. (For more information on neurotransmitters and their role in HD, click here). In order for the receptors to be able to recognize neurotransmitters and send along the messages that they contain, the nerve cell membrane must be fluid. If the nerve cell membrane is too rigid, the receptors on the membrane become less capable of recognizing neurotransmitters and passing along messages to the nerve cell. Often, the messages contained in neurotransmitters are critical to the survival of the nerve cell. Thus, membrane composition is extremely important because it influences nerve cells´ ability to communicate with each other and, ultimately, survive.
Studies reveal that optimal membrane composition is obtained when one consumes equal amounts of saturated and unsaturated fat. However, nutritional studies show that the average North American eats three times as much saturated fat as unsaturated fat! The addition of trans fat to the diet has made the situation even worse. Let us consider each fat in the context of our cells. Although too much saturated fat is bad, a certain amount is necessary for the optimal functioning of the membrane. On the other hand, the cell membrane has absolutely no use for trans fat. When trans fat gets incorporated into nerve cell membranes, the membranes become less capable of performing many essential functions, making the nerve cells more prone to a variety of insults.
How fat affects people with HD^
Nerve cell Communication^
Excessive consumption of saturated fat and trans fat can be particularly hazardous for people with HD. Even without any dietary influences, the HD disease process causes some nerve cells in the brain to become less able to communicate with each other, which contributes to these nerve cells losing function and eventually dying. Consuming excessive amounts of saturated fat can worsen this situation by making it even harder for nerve cells to communicate with each other via neurotransmitters. If the nerve cell membrane consists of too much saturated fat or trans fat, the nerve cell may be unable to receive messages from neurotransmitters. Often, these messages are essential for the survival of the cell. (For more information on the neurobiology of HD, click here.) Thus, it is clear that the amount and type of fat in the diet may influence the ability of nerve cells to survive. Replacing saturated fat and trans fat with unsaturated fat in the diet can enhance the ability of the nerve cell membrane to pass along necessary messages. It can also increase the fluidity of the nerve cell membrane, which makes it easier for the nerve cell to receive an adequate supply of oxygen and other essential nutrients. With the nerve cell membrane functioning as efficiently as possible, the nerve cell may be better able to deal with the harmful effects of HD. Thus, it may be possible for a person with HD to delay the onset and progression of HD symptoms simply by altering his or her fat consumption.
In addition to negatively affecting membrane function, a diet high in saturated fat may also induce oxidative stress and decrease levels of a protein known to assist in nerve cell survival called brain-derived neurotrophic factor (BDNF). Increased oxidative stress and decreased BDNF would be highly damaging to a person with HD. When trying to combat a neurodegenerative disease such as HD, maximizing levels of BDNF is ideal because it may help combat the damage done by the disease. Thus, in the interest of maintaining levels of BDNF, one might consider limiting one´s consumption of saturated fat. In addition, keeping oxidative stress to a minimum is important for people with HD. Oxidative stress, a harmful process that injures cells and eventually causes them to die as a result of free radical damage, is thought to contribute significantly to the disease process of HD. (For more information about free radicals and HD, click here.) Although a certain amount of oxidative stress will inevitably occur due to aging, it is important for people with HD to be conscientious about not worsening oxidative stress from the food they eat. Since diet is a very controllable aspect of one´s lifestyle, limiting consumption of saturated fats is a great way for people with HD to ensure that they do not aggravate the damaging processes in their nerve cells any further. Although much more research needs to be done in this area, it seems likely that adjusting for less saturated fat in one´s diet could significantly slow down the progression of HD.
Getting the right type of unsaturated fat – essential fatty acids.^
In general, it is true that any type of unsaturated fat is better for the brain and body than either saturated fat or trans fat. However, there are many different types of unsaturated fat and some types of unsaturated fat are better for you than others. Monounsaturated fatty acids have only one double bound and thus only one gap in the fatty acid chain. Polyunsaturated fatty acids have many double bonds and many gaps within the fatty acid chain. All saturated and monounsaturated fats can be made within the body and, therefore, they do not need to be supplied through the diet. However, the body is unable to make two types of polyunsaturated fat and these must be obtained through the diet. The first type of polyunsaturated fat is alpha-linolenic acid (ALA), which belongs to the omega-3 family of fatty acids. ALA is found abundantly in flax seed (a fiber derived from plants) and flax oil, and is found in small quantities in canola oil, wheat germ, and dark green leafy vegetables such as spinach and broccoli. The second type of polyunsaturated fat that the body cannot make is linoleic acid (LA) and it belongs to the omega-6 family of fatty acids. LA is found in soy oil, sesame seeds, corn oil, and in most nuts. Because the body is unable to make these two fatty acids, they are an essential part of the diet. Hence, they are called essential fatty acids (EFA´s).
Once the body is supplied with the essential fatty acid ALA, it can convert it into DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid). Both DHA and EPA are great at lowering one´s risk for heart disease. In addition, DHA is essential for nervous system maintenance and development. Infants who have low amounts of DHA in their diet have reduced brain development. Accordingly, human milk is extremely rich in DHA. DHA is the most abundant fatty acid in nerve cell membranes and is thought to contribute significantly to the fluidity of the cell membrane. DHA is also found in the synapses between nerve cells and is thought to greatly aid the nerve cells in sending signals to each other. The problem is that DHA levels naturally decline as one gets older. If DHA is not supplied through the diet (from consuming ALA), then the nerve cell membranes begin to function sub-optimally. Perhaps this may explain why societies whose diets are high in DHA (such as the Inuit of the arctic who eat a lot of fish, a great source of DHA) have a lower incidence of neurodegenerative disorders.
The other essential fatty acid, LA, is converted to GLA (gamma linoleic acid) within the body. GLA eventually leads to the production of prostaglandins, which are molecules that help regulate inflammation and blood pressure. (For more information on essential fatty acids and inflammation, click here.) While LA is termed “essential,” it is not entirely good for the body. In fact, Americans tend to consume way too much of it. This overconsumption is a problem because it turns out that both ALA and LA compete for the same enzymes to produce their final product. In other words, if there is too much LA, then the enzymes will be busy converting LA into GLA and there will be no enzymes left to convert ALA into DHA. (For more information on how ALA and LA compete for enzymes, click here.)Thus, a balance of ALA and LA is essential for proper health. Studies show that the optimal ratio of LA to ALA is somewhere between 2:1 and 1:1. It is estimated that the ratio of LA to ALA for most Americans is around 20:1. This imbalance makes sense because typical foods such as cereal, eggs, poultry, bread, and baked goods are made from oils rich in LA. Foods rich in ALA are much harder to find. Often, dietary supplementation may be needed in order to get enough ALA.
In addition to consuming enough ALA, humans must be able to absorb it. Findings suggest that an inadequate intake of vitamin E results in decreased absorption of ALA. Thus, some experts suggest that vitamin E supplementation may be useful in conjunction with ALA supplementation.
As mentioned earlier, nerve cell membranes are critical in terms of maintaining the safety of the nerve cell. Not only are they responsible for letting in essential nutrients and expelling harmful substances, but they also help nerve cells communicate with each other. Thus, in a person with HD, it is especially important for the nerve cell membranes to be operating optimally because it can greatly aid in the survival of the nerve cells. DHA, a product of ALA, has been shown to keep nerve cell membranes operating at an optimal level. It stands to reason that if a person with HD obtains adequate amounts of ALA and fixes the skewed imbalance of LA to ALA, he or she may be able to prolong the life of his or her nerve cells, and this too would likely delay the progression of the disease.
A wrap-up on fatty acids and HD^
Fats play a significant role in the brain. Specifically, the amount and type of fat one consumes directly affects the composition of nerve cell membranes. The composition of nerve cell membranes is especially important for people with HD because it has the potential to protect the nerve cell from damage. Too much saturated fat or trans fat in the diet leads to stiff, rigid membranes and a loss of membrane fluidity. In addition, too much saturated fat and trans fat alters the shape and size of the nerve cell membrane, which ultimately makes it so that the nerve cells are less able to communicate with each other. By replacing saturated fat with unsaturated fat in the diet, a person with HD can help his or her nerve cell membranes to function as efficiently as possible. Furthermore, certain types of unsaturated fat are more beneficial than others. In particular, the essential fatty acid (EFA) called ALA, which leads to DHA as described above, is the most abundant and perhaps most important in the brain. Because ALA competes with LA, one must limit one´s consumption of LA in order to ensure adequate amounts of ALA.
In short, the research reviewed in this chapter indicates that a person with HD should strive to reduce the amount of saturated fat and trans fat in his or her diet and to increase the ratio of ALA to LA in his or her diet in order to ensure the optimal functioning of the nerve cell membranes. Better functioning membranes means healthier nerve cells and having healthier nerve cells may well postpone the onset of HD symptoms.
Research on essential fatty acids:^
Vaddadi, et al. (1999) examined the effect that essential fatty acid (EFA) supplementation can have on the symptoms in people with HD. In the study, there were 17 HD patients who all showed clinical signs of HD, such as chorea. Genetic testing confirmed that these 17 patients did indeed have HD. During the study, the patients were told to stick to the same routine and continue taking the same amounts and types of medication. Randomly, nine of the subjects were assigned to the treatment group and they were given capsules that contained essential fatty acids. The other eight subjects were assigned to the control group and they received placebo capsules that did not contain essential fatty acids (this group was used to compare to the group receiving treatment). The study was designed to last two years and the patients´ symptoms were assessed at the beginning of the study and at six-month intervals. Their symptoms were assessed using two Huntington´s disease rating scales.
After twenty months, the study had to be stopped on ethical grounds because it was clear that the treatment group was receiving a significant benefit from the essential fatty acid capsules. The subjects in the treatment group improved in motor skills and functional performance while the subjects in the control group deteriorated. The results indicated an actual improvement over the starting measurements for the treatment group and not merely a slowing of deterioration. Of the nine subjects in the treatment group, only one subject did not improve over baseline. Much of the separation in results between the two groups occurred during the first six months of the study, indicating that it does not take long for the effects of essential fatty acid supplementation to be seen. However, the study did have a few shortcomings. The sample size was small and the effect of any earlier treatments that the subjects may have tried is unknown. Also, the study was terminated early so the long-term benefits of essential fatty supplementation are unclear. The study also does not indicate how high a dose is required to produce an effect. Clearly, much more research needs to be done in this area.
Clifford, et al. (2002) looked at how essential fatty acid (EFA) supplementation affected a mouse model of HD. These specific mice have an HD-like allele and they develop late-onset nervous system deficits in a manner similar to the motor abnormalities of HD. The mice were randomly divided into two groups: a treatment group receiving a mixture of fatty acids and a control group receiving a placebo. Through mid-adulthood, mice in the control group experienced progressive shortening of stride length and complications in movement ability. These deficits were either not evident in the mice in the treatment group or were significantly decreased. The findings of the study indicate that early and sustained treatment with essential fatty acids may be able to protect against motor deficits in mice that have an HD-like allele, and thus may also be able to protect against motor deficits in people with HD.
For further reading^
- Aiguo, W. et al. “The interplay between oxidative stress and brain-derived neurotrophic factor modulates the outcome of a saturated fat diet on synaptic plasticity and cognition.” European Journal of Neuroscience. 2004; 19(7): 1699-707.
This is a technical scientific article that explains how a diet high in saturated fat can lead to oxidative stress and decreased levels of BDNF.
- Clifford, J.J. et al. “Essential fatty acids given from conception prevent topographies of motor deficit in a transgenic model of Huntington´s disease.” Neuroscience. 2002; 109(1): 81-8.
This article is fairly easy to read and it describes the study in which a mouse model of HD that received essential fatty acids showed improvements in motor abilities.
- Vaddadi, K.S. et al. A randomised, placebo-controlled, double blind study of treatment of Huntington´s disease with unsaturated fatty acids.” Neuroreport. 2002; 13: 29-33.
This article is of medium difficulty. It describes the study in which essential fatty acid supplementation was examined among HD patients.
-D. McGee, 04/27/05