New Strategy of Micronutrients Combined with Dietary and Lifestyle Adjustment for Alzheimer s Disease Therapy and Partially Restoration

Review Article

Austin J Plant Bio. 2023; 9(1): 1036.

New Strategy of Micronutrients Combined with Dietary and Lifestyle Adjustment for Alzheimer’s Disease Therapy and Partially Restoration

Guanghui Xiu3; Yueqin Zeng2*; Jin-Tao Li1*

¹The Institute of Neuroscience of Kunming Medical University, China

²School of Biomedical Engineer, Kunming Medical University, Kunming ,Yunnan, China

²Department of Intensive Care Unit, the Affiliated Hospital of Yunnan University (the Second People’s Hospital of Yunnan Province), Yunnan University, Kunming, Yunnan Province, China

*Corresponding author: Jin-Tao Li No 1168 of Chun Rong West Road, the Institute of Neuroscience of Kunming Medical University, 650500, China

Yueqin Zeng School of Biomedical Engineer, Kunming Medical University, Kunming ,Yunnan, 650500 China. Email: kmlijintao@163.com; z_yueqin@hotmail.com

Received: June 28, 2023 Accepted: July 28, 2023 Published: August 04, 2023

Abstract

Alzheimer’s Disease (AD) is the leading cause of dementia resulting in memory loss, difficulty with thinking, and behavioral changes. To date, AD is continuously known as an incurative disease of the aged, and therefore has been widely considered as a challenge for clinical neurology both in the therapy, prevention and prognosis as well, thus bringing about heavy burden to not only the patients, their family, but also even the society. In this review, it has been proposed a new strategy synthetically implemented for the prevention and even partially restoration of Alzheimer’s Disease (AD), in which multiple micronutrients, combined with diet and lifestyle adjustment, were used for AD patients and people who already had the pro-phase symptom. Based on the notions, evidence and beneficial methods are put forward. It is promising to install a better and more efficacious AD administration system, with aim to reduce the incidence rate and elevate the life quality of AD patients in a sooner future.

Keywords: Combining therapeutic strategies; Micronutrients; Lifestyle adjustment; Alzheimer’s disease; Therapy and restoration

Introduction

Alzheimer’s disease (AD), known as one of the most common cause of dementia, is characterized by the senile plaque and Neurofibrillary Tangles (NFTs) mainly formed and deposited in the hippocampal area of AD patients. Individuals, who are 65 years or older, have higher and higher risk of developing this neurodegenerative disease due to the coming of aging society worldwide. Progressive cognitive, learning and memory disorders occur and become the most distinctive manifestation in this disease, accompanied with other neurological and/or mental symptom, such as weakness, depression, etc. Until now, it is still a challenge that seems to unable to overcome to effectively reduce the incidence or the rate of progression of AD, with few curative therapeutic strategies. Even so, several pathological reactions that contribute to degeneration and death of neurons in AD have been identified in last few decades, including such factors as increased oxidative stress, chronic inflammation, Aβ1-42 peptides generated from the cleavage of Amyloid Precursor Protein (APP), high cholesterol levels, etc., which are currently attracted more and more attention and becoming the main target factors focused on both in experimental research and clinical trials.

Despite these advances in our understanding of AD, no evidence-based strategy has been proposed to reduce the risk of AD or to improve the efficacy of drug therapy in the management of AD. Current drug therapies are mainly based on the symptoms rather than on the causes of the disease. For example, acetylcholinesterase inhibitors and an antagonist of glutamate receptor N-methyl-D-Aspartate (NMDA) are used to attenuate the symptoms of dementia and relieve the anxiety and fear associated with AD, respectively. They can exert modest beneficial effects on attenuating these symptoms, but with unpleasant side effects. Of note, they did not effect on increased oxidative stress or chronic inflammation which plays a key role in the development and progression of AD.

It has been found in recent years that the antioxidant strategy, when combining with standard therapy, could improve the management of this disease more than that produced by standard therapy alone. This proposed and preliminarily used novel therapeutic strategy is mainly based on Antioxidants that are long proved to have the ability to neutralize free radicals and reduce chronic inflammation. Therefore, it is indispensable to develop antioxidant-based therapeutic strategies and simultaneously reduce the risk of AD in high-risk populations, such as older individuals and individuals with a family history of AD levels for significant elevation of more intensive and precise disease administration of AD.

In recent years, some reports indicated that a micronutrient preparation containing dietary and endogenous antioxidants, vitamin D, B-vitamins, and certain minerals played roles in reducing the risk of AD and resisting the unfavorably factors that raising along with age, such as chronic oxidative stress [1]. However, there are few research and outcome reported involving the effects of micronutrient combining with antioxidants, and other beneficial methods on the amelioration of AD prevention, treatment and prognosis. It is needed systematic research in a larger population with multi-center studies, and for a long term follow-up and elaborate survey. Apart from these, the pathogenesis of AD still awaits further elucidation.

Therefore, it is an indispensable strategy to get AD relieved not only in its incidence rate, but also increase the therapeutic effects and the life quality by the help of effective methods with which to reduce the level of oxidative stress all along during all the course of AD. It seems that micronutrient combining with antioxidants, and other beneficial method is promising on the amelioration of AD treatment and prognosis as well, which are deserved to be widely and intensively studied.

Current Treatments of AD

Current treatments of AD are totally unsatisfactory, because they are based on the symptoms rather than on the causes of the disease. These treatments have failed to stop the progression of the AD. Commonly prescribed drugs are cholinesterase inhibitors (donepezil, galantamine, and rivastigmine) and NMDA antagonist (memantine). The purpose of cholinesterase inhibitors is to improve cognitive function by increasing the acetylcholine levels in cholinergic neurons. The efficacy of these drugs depends upon the viability of surviving cholinergic neuron. The purpose of NMDA receptor antagonist is to stop the action of glutamate which induces fear and anxiety in patients with AD. In randomized, double-blind, parallel-group clinical trials, all Acetylcholinesterase Inhibitors (AChEIs) have shown varying degrees of efficacy than placebo in improving cognitive function in patients with mild to moderate AD. Among donepezil, galantamine, and rivastigmine, donepezil was found to be slightly more effective than others, [2] but others have reported no such difference between these drugs (Birks J, et al., 2006). In the Hispanic population, the safety and beneficial effects of donepezil on cognitive function were similar to those found in the general population [3]. The annual cost of donepezil, galantamine, and rivastigmine was not significantly different [4]. These drugs do not affect the level of oxidative stress or chronic inflammation primarily responsible for neurodegeneration in AD brain; therefore, their efficacy does not last for a long period of time. The progression of the disease continues to occur because of oxidative stress- and chronic inflammation-induced progressive neuronal death. The addition of agents that can reduce oxidative stress and chronic inflammation to the current therapeutic modalities may prolong the effectiveness of AChEI in improving cognitive function in AD patients. Therefore, we propose that antioxidants that neutralize free radicals and reduce inflammation and a NSAID that reduces inflammation should be utilized in combination with standard therapy in order to improve the current management of AD.

Statins are commonly used in the prevention and treatment of heart disease. However, the outcomes achieved, such as reducing senile plaques and inflammation marker TNF-alpha by using atorvastatin and pitavastatin were only obtained from the AD transgenic mice [5], without verification in human AD. Another agents seems useful to AD were known as neurotrophic molecule J147. It has been found that it could significantly improve cognitive function even when administered at a late stage of the disease [6]. The effects of J147 was found mediated by inducing Nerve Growth Factor (NGF) and several Brain-Derived Neurotrophic Factor (BDNF)-responsive proteins which are considered important for learning and memory. But this outcome was just limited in AD mice model, either.

Limitations of Current Medications in AD

It has been proposed that the gradual loss of cognitive functions in AD is due to the loss of cholinergic neurons; therefore, cholinergic drugs (acetylcholinesterase inhibitors) are used to improve the function of surviving neurons in AD patients. However, these agents do not protect cholinergic neurons against the damaging effects of oxidative and nitrosylative stresses and chronic inflammation. Consequently, neurons continue to die, and the beneficial effects of cholinergic drugs do not last long.

Recommended Micronutrients and Low Dose of nsaid in Combination with Standard Therapy in Patients with Dementia with or without AD

Nowadays, acetylcholinesterase inhibitors are commonly utilized clinically to improve cognitive function by enhancing the activity of surviving cholinergic neurons in AD patients. However, these drugs only improved cognitive function by enhancing the activity of surviving cholinergic neurons in AD patients, whereas do not protect cholinergic neurons against the damaging effects of oxidative and nitrosylative stresses and chronic inflammation. Consequently, neurons continue to die despite this treatment, and thus, beneficial effects of cholinergic drugs last as long as neurons are alive. A supplement with an antagonist of glutamate receptor NMDA can be useful in reducing anxiety and fear in AD patients. This drug does not affect oxidative stress or chronic inflammation.

Antioxidants are well known to reduce oxidative stress, chronic inflammation, and release and toxicity of glutamate. And Aspirin can enhance anti-inflammation effects of antioxidants. Therefore, addition of a multiple micronutrient preparation and a low-dose aspirin in combination with standard therapy may prolong the beneficial effects of current drugs in patients with dementia with or without AD by protecting surviving neurons from damage produced by increased oxidative stress, chronic inflammation, and glutamate. The proposed combination of micronutrients recommended for primary prevention is applicable to those who are at the various stages of AD and taking medications. The daily doses are divided into two doses (half in the morning and half in the evening preferably with meal) and are administered orally (Table 1).

Citation:Xiu G, Zeng Y, Li JT. New Strategy of Micronutrients Combined with Dietary and Lifestyle Adjustment for Alzheimer’s Disease Therapy and Partially Restoration. Austin J Plant Bio. 2023; 9(1): 1036.