Research Analyst, AMAC Foundation
Alzheimer’s disease (AD), the most common form of dementia, is “characterized by a progressive loss of memory, decline in cognitive function, behavioral changes, and the loss in ability to carry out activities of daily living (ADL)” (Remington, Chan, Lepore, Kotlya, & Shea, 2010, p. 367). AD is estimated to affect at least 100 million people by the year 2050 (Essa et al., 2012; Mi, VanWijk, Cansev, Sijben, & Kamphuis, 2013) and the financial burden it places on the United States alone is significant – $200 billion in 2012 with an estimated increase to $1.1 trillion in 2050 (Mi et al., 2013). With the increased prevalence of AD across the world and the devastating effects it has on the lives of AD sufferers and their caregivers, many studies have looked for ways to prevent and cure the disease. Due to the side effects of medications, recent studies have turned to natural resources as a possible remedy. In addition, “the importance of nutritional intervention, especially during aging, is highlighted by both the exacerbation of otherwise latent AD risk factors by age-related nutritional decline and, more recently, studies demonstrating efficacy of nutritional supplementation” (Remington et al., p. 367). The following discusses many natural products, such as fruits and vegetables, that have been studied in rats, healthy adults, and Alzheimer’s diagnosed adults to see if natural options are a possibility.
“Mounting evidence points to the important role of nutrition in relation to cognitive function, especially during aging” (Mi et al., 2013, p. 1081). Many studies have concentrated on the potential of fruits and/or fruit juice to reduce disease progression because of the vitamins contained in fruit. Folate (also known as folic acid) is an essential vitamin needed for DNA and mitochondrial DNA integrity. In addition, folate deficiency is a risk factor for neural tube defects, cognitive decline, and dementia (Hinterberger & Fischer, 2013). Phospholipids are also an essential part of brain health and cognitive functioning. Folate, vitamin B12 and vitamin B6 can help improve the availability of choline and DHA (docosahexaenoic acid) for neuronal membrane phospholipid synthesis (Mi et al., 2013). There is mounting evidence showing that phytocompounds, including polyphenolic antioxidants in fruits and vegetables, could hinder neurodegeneration, as well as improve memory and cognitive function. “The molecular mechanisms behind the curative effects rely mainly on the action of phytonutrients on distinct signaling pathways associated with protein folding and neuroinflammation” (Essa et al., 2012, p. 1829). Furthermore, Vitamins C, E, selenium, and B vitamins “act as cofactors by increasing the availability of membrane precursors or by directly affecting the neuronal membrane or membrane synthesis, and are all reported to be lower in AD” (Mi et al., 2013, p. 1082).
Recent studies have shown that elderly AD patients have lower levels of vitamins A, C, E, folate, and B12, as well as lower plasma levels of other nutrients and vitamins than equivalent control group elderly adults without AD. However, it is not completely known if this is due to dietary issues after onset of the disease, if the vitamin deficiencies are causing and/or worsening dementia, or both (Mi et al., 2013). In reviewing nine case-controlled studies, it was determined by Mi et al. that AD patients have low levels of folate and B12. The increased need for specific nutrients may be due to synapse loss caused by the disease.
Remington et al. (2010) conducted a study in an institution involving 21 residents ages 72 to 93 that were clinically diagnosed with moderate to late-stage Alzheimer’s disease. The participants consumed two 4-ounce glasses of apple juice daily for one month. Patients with diabetes were excluded from participation and other factors remained constant, such as diet, vitamin, and medication regimens. At the start of the trial and after one month, the participants completed the Dementia Rating Scale 2 (DRS-2) to determine any changes in cognitive performance. In addition, caregivers at the institution completed the Neuropsychiatric Inventory (NPI), “which determines the degree to which abnormal behavior affects the patient’s well-being”, as well as the Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), “which assesses the ability to engage in day-to-day activities” (Remington et al., p. 368). Even though results showed no change in cognitive performance, there were statistically significant changes in behavior. Participants showed major positive effects regarding anxiety, apathy, agitation, depression, and delusion.
“The beneficial effect of apple juice on participant mood, without improvement in cognition, is consistent with the studies demonstrating that behavioral and psychological symptoms of dementia (BPSD)…need not necessarily correlate with cognitive performance” (Remington et al., 2010, p. 368). Other studies using apple juice have illustrated its potential to improve oxidative damage and synaptic signaling (Essa et al., 2012). However, the researchers are cautionary in that this particular study has a small sample size and inability to include a placebo. On the other hand, the results are consistent with other studies and do give hope to the population affected by the disease.
Whether vitamins are a viable treatment and preventive option for dementia is still up for debate due to the difficulty of proper clinical research using AD patients. For example, in studying the prevention of dementia, one would have to observe patients for decades thus increasing the potential for uncontrollable factors like a patient’s lifestyle, other health issues, other supplements, and medication use. Hinterberger and Fischer (2013) reviewed many studies on the subject and identified seven clear gaps in research that cause differing results in clinical studies. They are:
- Heterogeneity of the subjects concerning age, recruitment and baseline cognition;
- Different methods of assessment of cognition or dementia;
- Different methods of determination of folate levels (food questionnaires, supplemental use and laboratory analyses);
- Lack of standardized threshold level and inconsistent definitions of “low” folate or “high” homocysteine levels with heterogeneous study entry criteria;
- “Misleading” folate levels due to short-term use of multivitamins without reporting;
- Mandatory folic acid fortification; and
- Short follow-up (p. 212).
Hinterberger and Fischer (2013) reviewed 14 epidemiologic studies that had observation periods from four to 9.3 years. In 11 of these studies, at least one of the three “major players” (folate, B12, and homocysteine) had significant, independent, and beneficial impact on cognition. They also reviewed seven randomized control trials that used B vitamin intervention from two to 5.4 years on cognitively healthy adults, adults with mild cognitive impairment, and/or adults diagnosed with AD. In six of these studies, supplementation showed cognitive benefits on all treatment groups, but mainly in the adults with high homocysteine levels or low folate intake at baseline.
Due to the studies and observations about the nutritional links to Alzheimer’s disease, a supplement was developed called Fortasyn® Connect. It is designed to “enhance synapse formation and function” and is comprised of “nutritional precursors and cofactors for membrane synthesis, including DHA, EPA (eicosapentaenoic), UMP (uridine-5’-monophosphate), choline, phospholipids, folic acid, vitamins B6, B12, C, E, and selenium” (Mi et al., 2013, p. 1082). Prior studies have shown that Fortasyn® Connect can reduce AD pathology and alleviate special learning deficits in young adult mice. The medical food Souvenaid®, which contains Fortasyn® Connect, has been used in several randomized control trials (RCT) and showed improved performance in delayed verbal memory tasks. This finding was confirmed and extended through a double-blind RCT involving 259 mild AD drug-naïve patients over a 24-week period. This study showed that Souvenaid® improved memory and was safe for long-term use. However, this and a subsequent similar trial using 527 patients with mild to moderate AD suggested that Souvenaid® is only beneficial for mild AD. Therefore, it is hypothesized that this type of nutritional intervention in which synapse formation and function are targeted would be the most beneficial to those showing the first signs of dementia, for example, in individuals with mild cognitive impairment due to AD (Mi et al.).
There is also a great deal of evidence that other natural products can help prevent and treat dementia. According to Bhandari (2013), other potential avenues include aged garlic extract (AGE), pomegranate juice, curry leaf (murraya koenigii), carrots (daucus carota extract), and saffron (crocus sativus). Studies using these natural products have shown positive effects on mice; therefore, they have potential for preventing and managing AD, but need further analysis. Essa et al. (2012) agrees that pomegranate (punica granatum), saffron, and garlic have the potential for helping dementia patients due to their neuroprotective effects. For example, pomegranate is enriched with the phenolic antioxidant ellagic acid (EA), which is a beta secretase inhibitor. They also argue that animal studies have shown that other fruits also have neuroprotective effects, such as blueberry, mulberry, strawberry, grape seed extract, papaya, and apple. Again, these products do still need further investigation due to non-human testing (Essa et al.).
“Taken together, observational studies suggest that lower nutrient status is a consistent finding during disease progression: It not only is a risk factor for onset of AD, but also presents in the early stage of AD including mild cognitive impairment” (Mi et al., 2013, pp. 1081-1082). Even though no definite conclusions can be drawn just yet, overall research does show that combining normal B12 levels with high serum folate can potentially reduce cognitive decline in the elderly (Hinterberger & Fischer, 2013; Mi et al., 2013) and can benefit those of all ages (Hinterberger & Fischer, 2013). Furthermore, there are no risks associated with this type of preventive intervention and the costs are significantly less than pharmaceutical alternatives (Mi et al.; Remington et al., 2010).
Bhandari, P. R. (2013, April-June). A comment on effect of plant extracts on Alzheimer’s disease: An insight into therapeutic avenues [Letter to the editor]. Journal of Neurosciences in Rural Practice, 4(2), 236-237. doi: 10.4103/0976-3147.112782
Essa, M. M., Vijayan, R. K., Castellano-Gonzalez, G., Memon, M. A., Braidy, N., & Guillemin, G. J. (2012, May 22). Neuroprotective effect of natural products against Alzheimer’s disease. Neurochemical Research, 37, 1829-1842. doi: 10.1007/s11064-012-0799-9
Hinterberger, M. & Fischer, P. (2012, May). Folate and Alzheimer: When time matters. Journal of Neural Transmission, 120(1), 211-224. Doi: 10.1007/s00702-012-0822-y
Mi, W., VanWijk, N., Cansev, M., Sijben, J. W. C., & Kamphuis, P. J. G. H. (2013, September). Nutritional approaches in the risk reduction and management of Alzheimer’s disease. Nutrition, 29(9), 1080-1089. Doi:http://dx.doi.org/10.1016/j.nut.2013.01.024
Remington, R., Chan, A., Lepore, A., Kotlya, E., & Shea, T. B. (2010, March 25). Apple juice improved behavioral but not cognitive symptoms in moderate-to-late stage Alzheimer’s disease in an open-label pilot study. American Journal of Alzheimer’s Disease and Other Dementias, 25(4), 367-371. doi: 10.1177/1533317510363470