Nutritional Help with Aging by Dr. Christopher Jackson, PhD, DOM
The conventional approach to treatment of disorders associated with aging tends to focus on treatment of symptoms, rather than correction of underlying causal factors. The issues of cognitive decline, Alzheimer's disease (Alzheimer's), and dementia are of prime importance in the elderly. As of 2010, the number of individuals afflicted with dementia was in excess of 24 million, and expected to double in 20 years (Fratiglioni, Mangialasche, & Chengxuan, 2010). Dementia is one of the more obvious characteristics of Alzheimer's, which is responsible for 60 to 70 percent of dementia cases according to Fratiglioni et al. (2010). However, dementia does not necessarily indicate that an individual has Alzheimer's, since vascular dementia is generally considered the second leading cause. Fratiglioni et al. (2010) suggested that a combination of the two they called mixed dementia may actually be the most common form at 53 percent of the cases of dementia.
By addressing the underlying causes, natural preventative solutions to treatment of the effects of aging could go a long way toward the reduction of both the personal and the public healthcare costs. These costs include the high costs of care and the drugs used conventionally for the treatment of dementia, Alzheimer's, and the cognitive decline that may occur with aging (Oremus & Aguilar, 2011). The following review will explore the underlying causal factors, as well as potential natural treatments for disorders associated with aging.
The Underlying Causes
Fratiglioni et al. (2010) explored a range of hypotheses on the underlying causes of dementia and Alzheimer's through a nutritional filter. The authors correlated a combination of genetic (especially with a first degree relative with Alzheimer's), environmental, vascular (hypertension, cerebrovascular disease, heart disease, stroke, or diabetes), inflammatory, and psychosocial factors. Additionally, according to Fratiglioni et al. (2010), the chances of late-life dementia, Alzheimer's, and declining cognitive function increase as total cholesterol declines after midlife (inversely proportional), yet elevated cholesterol going into midlife also increases the likelihood of cognitive decline, Alzheimer's, and dementia late in life.
Folstein and Folstein (2010) referenced a study of the aging brain focused on nutrition and memory loss of 365 participants. The study filtered out participants who had been diagnosed with dementia. The evaluation of brain atrophy using MRI revealed a correlation with vascular degradation, suggesting the possibility that MRI technology could be used to evaluate nutritional treatment solutions (Folstein & Folstein, 2010).
In the elderly, malnutrition and weight loss may manifest as a loss of muscle mass (sarcopenia) correlated with dementia, but according to Faxén Irving (2003), which comes first (sarcopenia or dementia) is unclear. It is possible that the inability to recognize, taste, or prepare food, or even remember how to eat, may result in malnutrition and eventually sarcopenia (Faxén Irving, 2003). Chwang (2012) contended that elderly nutrition and diet may lead to deficiencies correlated to disorders such as Parkinson's, dysphagia (inability to swallow), sarcopenia, and dementia.
At least one of the mechanisms of damage for dementia and other forms of cognitive impairment, as well as neurological disorders, is oxidative damage produced by free radicals that strip electrons from molecules throughout the human body. The free radicals result from exposure of human beings to a plethora of environmental toxins, nutritional deficiencies resulting in a lack of antioxidants, and primarily from normal metabolic processes related to mitochondrial activity such as cellular respiration (particularly in the aging brain), damaging cell membrane lipids, DNA, and proteins in the brain and throughout the body (Daffner, 2010; Stough et al., 2012).
Another mechanism, when not functioning optimally, the process of methylation takes part in the creation of neurotransmitters, derivation of methionine from homocysteine, and production of cell membranes. Dao-Mei et al. (2010) studied 662 elderly participants, 57.1 percent women, and statistically confirmed a direct correlation between homocysteine levels and cognitive dysfunction. Cardiovascular function is also negatively affected by elevated homocysteine levels, which may cause inflammatory processes that lead to pathology when elevated (Dao-Mei et al., 2010; Jia, McNeill, & Avenell, 2008).
According to Kagawa (2012), telomeres are involved in additional mechanisms of damage through shortening and eventual programmed cell death (cellular senescence). Aging is established partly by the lengths of telomeres, the base material at the end of DNA (chromosomes) that is involved in cellular replication. Telomere length shortens over time with each cycle of replication, reducing mitochondrial activity with each cycle, until the material is gone and cell death occurs (Kagawa, 2012).
Several processes are important to proper neurological function and production of neurotransmitters. Such processes can be influenced by excesses or deficiencies of certain vitamins and minerals (micronutrients), as well as macronutrients, such as fatty acids and chains of amino acids that form proteins (Camardese et al., 2012). Thus, nutritional deficiencies or excesses can be contributors to the aging process, and nutritional substances may help to delay aging processes.
Antioxidant vitamins are involved in many processes in the human body. Neurons and cerebrospinal fluid contain high amounts of the important antioxidant ascorbic acid (vitamin C). Vitamin C is an essential cofactor in enzymatic processes, especially since human beings lack the ability to derive vitamin C from glucose due to the lack of enzyme gulonolactone oxidase (Bowman, 2012; Morris, 2009).
The process of methylation can be disrupted by a lack of methyl donors, particularly B vitamins such as methylcobalamin (B12), niacin (B3), and pyridoxine (B6) (Dao-Mei et al., 2010). Selhub, Troen, and Rosenberg (2010) also examined the associations between vitamins B6, folate (B9), and B12, homocysteine, and aging. The authors found that B vitamin deficiencies, and elevated homocysteine levels were each directly correlated with dementia, cognitive dysfunction, and Alzheimer's (Selhub et al., 2010). B12 deficiency is common among the elderly, as is the use of antacids such as proton pump inhibitors that are likely to cause B12 deficiency, according to a recent large-scale study by Lam, Schneider, Wei, and Corley (2013), worsening an already prevalent situation. The study of 25,956 B12 deficient individuals compared antacid use with 184,199 individuals without B12 deficiency and found that proton pump inhibitor use of greater than 2 years lead to a 65 percent increased likelihood of B12 deficiency, even greater with increased dosage.
Coenzyme Q10 (CoQ10) helps to energize every cell in the body and supports muscle function, including the heart (Challem, 2009). CoQ10 is also neuroprotective, particularly in the dopaminergic neurons (Chao, Leung, Wang, & Chang, 2012). According to Potgieter, Pretorius, and Pepper (2013), a secondary effect of the common use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) for hypercholesterolemia and other disorders is the reduction of CoQ10 levels, due to the effect of statins on mevalonate, a precursor to CoQ10 production. Genetic mutations can lead to a primary form of CoQ10 deficiency as well. CoQ10 is a cofactor in the electron transport chain in mitochondria, thereby affecting the energy level of the individual via adenosine triphosphate (ATP) production. Therefore, if an individual has a deficiency in CoQ10, energy levels suffer throughout the body, including the brain, skeletal muscles, and the heart. Additionally, a deficiency in tyrosine could lead to a CoQ10 deficiency since tyrosine is a precursor in the biosynthesis of CoQ10 (Potgieter et al., 2013).
Antioxidant minerals play important roles as well. The mineral selenium is an antioxidant mineral important to neuronal and cognitive function that also affects thyroid hormone levels. According to Torres-Vega, Pliego-Rivero, Otero-Ojeda, Gómez-Oliván, and Vieyra-Reyes (2012), high levels of selenium, zinc, and copper exist in the hippocampus. Iron deficiency can result from elevated zinc, leading to reduced neuronal branching and cognitive dysfunction. Iron is found in the dopamine centers of the brain, such as the substantia nigra, and in the oligodendrocytes, affecting the central nervous system (CNS). Cu levels positively affect dopamine beta hydroxylase activity, thereby also affecting neurotransmission in the CNS. Additionally, copper affects the synthesis of neuropeptides via peptidyl glycine a-amidating mono-oxygenase. Zinc blocks gamma-aminobutyric acid (GABA) receptors, affecting excitabiliy if elevated (Torres-Vega et al., 2012). Magnesium positively affects levels of dopamine, serotonin, GABA receptors, and catecholamines, possibly leading to mood fluctuations when deficient (Camardese et al., 2012).
Antioxidant enzymes are also quite important to cognitive and neuronal function, and use many minerals and vitamins as cofactors. According to Torres-Vega et al. (2012), iron is found in the enzymes tyrosine hydroxylase, phenylalanine hydroxylase, and tryptophan hydroxylase. Tyrosine hydroxylase and phenylalanine hydroxylase are involved in the production of catecholamines, dopamine production, and thyroid function. Tryptophan hydroxylase positively affects tryptophan production, a precursor to serotonin and melatonin. Zinc and copper promote superoxide dismutase activity (a powerful antioxidant) at the cellular level. Selenium is a co-factor of glutathione peroxidase, thioredoxin reductase, and iodothyronine deiodinase, the latter pulling iodide from thyroxine (T4), resulting in triiodothyronine (T3) hormone. T3 is the more active thyroid hormone for metabolic optimization, which also affects the absorption of glucose into the brain, supporting cognition. The CNS also depends on these antioxidant enzymes to protect neurons from antioxidant damage (Torres-Vega et al., 2012).
According to Lakhan and Vieira (2008), fatty acids are also important to neurological development, maintaining a balanced mood, and general cognitive and synaptic function (and prevention of decline). The most efficacious oils for these purposes are omega 3 polyunsaturated fatty acids (found primarily in fish oil). The omega 3 oils include docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which is also a precursor to DHA. González, Huerta, Fernández, Patterson, and Lasheras (2010), was a study of 177 elderly women and 127 elderly men who were institutionalized and mostly aged in the 70s. The study examined the correlation between cognitive performance and intake of fatty acids. DHA and EPA levels were found to be directly correlated with cognitive function. Morris (2009) correlated greater frequency of Alzheimer's with higher levels of saturated fats, yet elevated DHA and high vitamin E amounts tended to be associated with less frequent occurrence of Alzheimer's. The level of aggressive behavior, according to Alfonso and Alberto (2005), and depression, according to Lakhan and Vieira (2008), were reduced when high density lipoprotein (HDL) levels (the so-called good cholesterol), were elevated, which resulted from increased consumption of Omega 3 fatty acids.
Faxén Irving (2003) highlighted the importance of differentiating between choices of fats, pointing out that a negative effect was seen on cognition along with a worsening of dementia with high fat intake, yet when omega 3 was the fat of choice the result was a very positive anti-inflammatory effect reducing the chances of dementia onset. Fratiglioni et al. (2010) also pointed to a lower risk of dementia, specifically at higher levels of omega 3 fatty acid EPA. Omega 9 monounsaturated oils (most prominently olive oil) are important for long-term health as well, and are an essential component of the Mediterranean diet. However, inflammatory conditions, cognitive decline, and neurological dysfunction are often the result of the overabundance of omega 6 fatty acids in the western diet (Daffner, 2010; Jia et al., 2008; Karr, Alexander, & Winningham, 2011; Morris, 2009).
Treating the Cause
Telomere shortening is an effect that can be delayed through caloric restriction, thereby lengthening lifespan (Kagawa, 2012). In addition to delaying the shortening of telomeres, Bernardes de Jesus et al. (2011) demonstrated in mice and Wang, Zhang, Sun, Liu, and Tong (2010) showed in human female lung tissue that telomeres could be lengthened when critically short and DNA damage could be repaired. Therefore, an essential element of aging could be reversed. The substances studied were extracts of the herb Astragalus membranaceus, also known in traditional Chinese herbal medicine as Huang Qi (Bernardes de Jesus et al., 2011; Wang et al., 2010).
Bowman (2012) showed that proper diet and nutritional intake could possibly delay the onset of Alzheimer's. According to Fratiglioni et al. (2010), the risk of cognitive impairment, dementia, and Alzheimer's were inversely correlated with elevated vegetable and fruit consumption. Viewing this more broadly, an inverse association was found with adherence to a Mediterranean diet, including high legume, vegetable, fruit, and fish intake, as well as a low beef and poultry intake (Fratiglioni et al., 2010).
Vitamins and minerals that may help to reduce the effects of aging are functionally related to the processes involved in aging. Specifically, antioxidants are naturally occuring vitamins and minerals that donate electrons, essentially helping to repair oxidative damage that contributes to the aging process (Lakhan & Vieira, 2008). When vitamin C is combined with vitamin E, cognitive function can be improved due to effective repair of the fatty membranes of vascular cells and a resultant reduction in the level of inflammation throughout the body, and particularly the brain (Bowman, 2012; Morris, 2009). Additionally, dementia may be delayed through the kinds of extracurricular activities that include physical, social, and mental components (Fratiglioni et al., 2010). Chao et al. (2012) agreed that some degree of neuroprotection exists with vitamin E supplementation, as well as the combination of vitamins C and E, but indicated differing views on the effectiveness of vitamin C alone.
According to Challem (2009), antioxidant CoQ10 assists longevity by helping to prevent and treat disorders including cardiological and immune system issues. CoQ10 also helps to keep energy levels and cognition optimal. Acetyl-l-carnitine (1 gram daily) in combination with CoQ10, alpha lipoic acid (200mg daily), and vitamin C (1 gram daily), helps to increase energy production, cognitive acuity, and muscle mass. Vitamins thiamin (B1), riboflavin (B2), and B3 help CoQ10 and carnitine to improve energy production. Additionally, B12 and B9, combine with B2 and B3 to improve gene synthesis and repair (Challem, 2009). A safe limit for CoQ10 supplementation of 1200 mg per day has been suggested by Potgieter et al. (2013).
Other substances are of importance according to Chiu, Lalone, and Goble (2007), who examined the biochemical mechanisms of various alternative treatments for Alzheimer's disease and schizophrenia, particularly Huperzine A, an alkaloid extract from the Chinese moss Huperzia serrata. Huperzine A helps to modulate dopamine and noradrenaline levels via neurotransmitter N-methyl-D-aspartic acid (NMDA), and inhibits the acetylcholinesterase enzyme, which dissolves unused quantities of neurotransmitter acetylcholine, leaving more available for use by the brain. Huperzine A did well in comparison with acetylcholinesterase inhibitor Aricept ( donepezil) in lab rat studies, and some human studies at 60 to 200 mcg doses. Huperzine A has the added benefit, versus Aricept, of NMDA modulation, which may have a neuroprotective effect against nerve death due to the activity of excitotoxins, such as flavor enhancer monosodium glutamate and artificial sweetener aspartame (Chiu et al., 2007).
Many other substances are of interest to improve upon or delay the effects of aging. According to Challem (2009), the potent antioxidant resveratrol can have the effect of increasing lifespan, at 100 to 200 mg per day. Resveratrol triggers the protective silent information regulator T1 (SIRT1) gene which prevents apoptosis through protein deacetylation and by binding directly to telomeres. Resveratrol also has blood sugar regulating properties, providing protection against diabetes and its sequela (Challem, 2009; Kagawa, 2012). Cat's claw (Uncaria tomentosa), a well-studied herb with antioxidant and antitumor effects (inducing apoptosis), also helps with DNA repair (Bacher et al., 2006; Challem 2009).
Other substances, such as proanthocyanidins aside from resveratrol, and curcuminoids (found in turmeric) help fight inflammatory conditions from cognitive to cancer to cardiovascular disease (Challem 2009; Stough et al., 2012). According to Sood et al. (2011), curcumin (the source of curcuminoids) helps to reduce inflammation in neurons. In this rat study the source of inflammation was aluminum and a small population was sampled, thus a larger human study of inflammatory responses with curcumin is suggested. Chao et al. (2012) attribute additional neuronal protection by curcumin to the restoration of glutathione.
Treatment through Intervention
Interventional programs could include nutritional training at assisted living facilities, which would address the elderly population directly, and could help to improve nutrition and diet, possibly preventing much of the cognitive decline seen in the aging populations. The training could also help to prevent further degradation of bones and joints or reduce the degree of osteoporosis seen in many elderly (Manios, Moschonis, Katsaroli, Grammatikaki, & Tanagra, 2007). Nutritional training of caregivers could help them to pass nutritional knowledge and benefit to the elderly, and improve their understanding of the needs of elderly patients. For the more isolated among the elderly population, a telephone intervention program could be developed to include counseling sessions to address the specific needs of each individual.
An interventional media campaign targeting the elderly population could be helpful in promoting healthy eating habits particularly beneficial to the elderly. Promoting increased consumption of antioxidant rich fruits and vegetables, as well as cold water fish rich in omega 3 fatty acids DHA and EPA, as well as vitamin D for bone and immune health along with promotion of the Mediterranean diet, could raise the level of awareness of nutritional needs, and make a difference in the incidence of dementia, Alzheimer's, and cognitive decline among the elderly (Brambila-Macias et al., 2011; Fratiglioni et al., 2010). Community involvement and participation by organizations supportive of the elderly, such as the American Association of Retired Persons (AARP), could help to ensure thorough implementation of the interventional programs, refresh elderly individuals whose memories might not be optimal, and expand upon the understanding and implementation of diet and nutrition improvements (Goode, Owen, Reeves, & Eakin, 2012).
There is certainly no shortage of substances that can affect the aging process. Most deficiencies of micro and macronutrients can be addressed through sufficient supplementation. B vitamin supplementation could help to bring down homocysteine levels, improve the methylation process, reduce inflammation, and improve cognitive function (Dao-Mei et al., 2010; Jia, McNeill, & Avenell, 2008). Supplementation with the specific precursors to cognition, such as choline to help synthesize the important neurotransmitter acetylcholine, could make the difference more significant. Huperzine A helps to keep the acetylcholine level up as well, improving cognitive function and memory. CoQ10 supports the energy factories in the body (mitochondria) and is important to the strength and structure of the skeletal muscles and the cardiovascular system. Vitamins C and E combine to maintain vascular cell walls and minimize inflammation, especially with the addition of turmeric (curcuminoids). A balance of minerals also helps to optimize neurotransmitter levels. Therefore, a good daily multivitamin/mineral is essential for the aging population, and can be enhanced by supportive extracts.
Copyright 2014 by Dr. Chrisopher Jackson, PhD, DOM
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