Perspective Chapter: Nutraceuticals as a Therapeutic Promise in Healthy Aging and Neurocognitive Disorders

Abstract

The world is facing a rapid population ageing. Noncommunicable disorders (NCDs) form the bulk of present-day morbidity. Besides dealing with neurodegeneration and neurocognitive disorders, modern-day therapeutics have also geared toward healthy ageing and preventive approaches. Several chemical substances belonging to classes of natural dietary origin display protective properties against some age-related diseases, including neurodegenerative ones. These compounds, known as nutraceuticals, differ structurally, acting on different pathways. There has been a paradigm shift in the understanding of dementias toward neuroinflammation, oxidative stress, immunomodulation, and gut-brain axis dysregulation. This offers promise for the nutraceuticals as a novel approach in the field of neurocognitive disorders and healthy ageing. However, the collective evidence is still evolving and as of yet not robust enough for nutraceuticals to be a part of clinical guidelines. The other caveats are lack of subjective understanding of use, and individual constituents of a product showing differential effects, which lead to ambiguous outcomes in clinical trials. This chapter critically looks at the role of various nutraceuticals in promoting healthy aging and management of neurodegenerative conditions (especially Alzheimer’s disease). The evidence so far is highlighted with the challenges in their use and future directions of research.

1. Introduction

Aging can be defined as the time-related deterioration of the physiological functions necessary for survival and fertility. It affects all the individuals of a species [1]. Age is a major risk factor for numerous illnesses, such as diabetes and cancer, various degenerative diseases, including Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PDs), and various other neurocognitive disorders (NCDs) [2]. However, genetics, lifestyle patterns, environment, and ecology play an equal or perhaps more important role in these diseases. Different biological theories have been put forward to explain the aging phenomena. Some of these are oxidative damage theory, general wear and tear theory, genetic instability, telomere shortening, mitochondrial genome damage, genetic program theory, etc. [1, 3, 4, 5, 6, 7, 8, 9, 10].

Cognition is the higher order brain function that alters with advancing age, which, in turn, influences the quality of life of an individual [11]. Cognitive aging is governed by the interplay of multiple factors, including lifestyle, diet, nutrition, endocrine and genetic parameters, oxidative damage, neurotoxic exposures, and medical and surgical interventions for disease [12, 13]. Nutritional status plays a critical role in the cognitive abilities of an individual. It is a modifier of cognitive aging. Studies have shown that nutritional imbalance adversely affects the structural and functional integrity of the brain critically impacting the cognitive capacities and process of aging [14].

Older people are at risk for various micronutrient deficiencies due to social, physical, economic, and emotional factors. The development of effective nutritional interventions for promoting healthy aging and preventing and treating NCDs is an emerging and challenging area of biomedical research [13].

The term “nutraceutical” was originally defined by Stephen L. DeFelice, as a combination of terms “nutrition and pharmaceutical [15].” As per the European Nutraceutical Association, they are defined as “naturally derived bioactive compounds that are found in foods, dietary supplements, and herbal products, and have health-promoting, disease-preventing, or medicinal properties [16].” On the other hand, “nutritional supplements” are nutritional compounds that supplement one’s diet by increasing total daily intake [17]. Nutraceuticals are intended to affect the structure and function of the body; however, they do not undergo premarket approval. These are perceived as safe and less likely to have adverse effects [18]. Nutraceutical categories include dietary supplements (e.g., vitamins, minerals, coenzyme Q , carnitine, and botanicals such as ginseng and ginkgo biloba), medicinal foods (e.g., transgenic plants), and functional foods (e.g., oats, bran, omega-3 fatty acids, and plant sterols) [15, 19].

“Nutritional psychiatry” is a distinct field of psychiatry that studies the role and impact of diet and various nutraceuticals in the treatment and prevention of a range of psychiatric disorders, including neurocognitive disorders (NCDs) [20, 21, 22].

The role of nutraceuticals in noncommunicable diseases and healthy aging has been increasingly studied. Though the evidence base for their use in neurocognitive disorders has been increasing, guidelines regulating their use, safety, adverse effects, and efficacy in clinical settings are ambiguous and limited. There is a general tendency to accept “nutraceutical products” as a part of nutritional supplements in healthy aging with an “assumption” of their safety; however, more research is needed in the field [17, 18]. The ambiguity in evidence makes it challenging for clinicians working in the field of neuropsychiatry to take a clear stand related to their use and effectiveness. Keeping this in background, this chapter provides an overview of various nutraceuticals used in healthy aging and neurocognitive disorders, summarizes the available evidence base for the same, discusses the possible mechanisms of action, and outlines the challenges involved in their clinical use. This chapter is expected to stimulate thoughts and further research into this promising area that can offer viable solutions in the field of neurocognition.

2. Types of nutraceuticals that have been studied in NCDs and healthy aging

2.1 Mechanism of action: how do nutraceuticals intervene?

The majority of nutraceuticals act as antioxidant agents; few of them are anti-inflammatory, anticarcinogenic, and antiangiogenic agents (Table 1) [13, 35]. The various ways in which they act on cognitive processes and aging are depicted in Figure 1. However, these are only basics, and further research is necessary to elucidate the deeper underlying mechanisms.

Class of nutraceuticals	Mechanism of action	Examples and diet sources
Antioxidants [23]	Inhibit the formation of free radicals by breaking the chain reaction or reduce the concentration of free radicals by donating hydrogen and electron	Vitamin A, E, C, Polyphenols, Beta carotene (green leafy vegetables and citrus fruits)
Plant polyphenols and catechins [24]	Antioxidant, Anti-inflammatory, Anticancer	Turmeric, green tea, Grapeseed (fruits, vegetables, legumes, cereals, and beverages)
Carotenoids [25]	Anticancer, Antioxidant, Cell growth regulation, modulation of gene expression, and immune response	Lutein, zeaxanthin, and lycopene, (green leafy vegetables, spinach, carrots, and apricots)
Plant stanols/sterols (Phytosterols) [26]	Reduce cholesterol absorption, anti-inflammatory, antineoplastic, and immunomodulating	Sitosterol, stigmasterol, campesterol, (vegetables, nuts, fruits, and seeds)
B vitamins [27]	One carbon metabolism, Methylation reactions	Vitamin B6, B9, B12
Calcium and vitamin D [28]	Bone metabolism, antineoplastic	Spinach, soybeans, fish
Omega-3 fatty acids [29]	Anti-inflammatory, Reduce blood triglyceride levels	Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), (fish oil, plants, flaxseed)
Prebiotics and probiotics [30]	Role in innate immunity, intestinal barrier function	Lactobacillus and Bifidobacterium family
Zinc [31]	DNA synthesis, cell proliferation, and differentiation	Whole grain, legumes, meat, egg, sea fish
Coenzyme Q10 [28]	Aerobic respiration, generation of ATP
Ginkgo biloba [32]	Improves function of nerve cells, platelets, and antioxidant
Vaccinium corymbosum (blueberry) [28]	Antioxidant,	blueberry
Cranberry (Vaccinium oxycoccos) and oregano (Origanum vulgare) [33]	Antimicrobial, antiviral, antimutagenic, antiangiogenic, and antioxidant
Nectarine and acai fruits [28]	Antioxidant
Rosa damascena	Antiepileptic, anti-amyloid	Rose oil
Cocoa polyphenols [28]	Antioxidant, altering chromatin structure	Cocoa powder
Quercetin and tannic acid [34]	Antiamyloid, antineoplastic, antioxidant	Fruits and vegetables
Caffeic acid and rosmarinic acid	Anticarcinogenic, antirheumatic, and anti-inflammatory	Fruits, vegetables, and herbs
Spermidine	Enhance autophagy	Citrus fruits, soybean

Table 1.

Various nutraceuticals (and their sources) that have been studied in healthy aging and NCDs.

Figure 1.

Mechanisms in which nutraceuticals act on cognition and neurocognitive disorders [35].

2.1.1 Effects of nutraceuticals in cognitive aging and progression to neurodegenerative disorders

Cognitive changes associated with normal aging when accelerated result in mild cognitive impairment (MCI), characterized by structural changes in the brain such as amyloid plaque deposition, demyelination, and neurodegeneration. MCI increases the risk for developing major neurocognitive disorders through increased pathology, which results in marked cognitive impairment. Gene expression that has been altered with concomitant oxidative stress causes DNA damage and protein aggregation, which leads to MCI and dementia. Nutraceuticals of plant and animal origin help in the attainment of healthy aging and prevention and slow down the neurodegeneration process with increased longevity and preservation of cognitive abilities [36, 37]. Nutraceuticals have the potential to reverse structural changes in the brain, prevent DNA damage, and slow down protein aggregations promoting healthy aging as well as preventing or delaying the onset of MCI and dementia [13, 35, 38, 39]. Their effects on the cognitive changes in the pathophysiological spectrum are highlighted in Figure 2.

Figure 2.

Effect of nutraceuticals in mild cognitive impairment, neurocognitive disorders, and healthy aging.

Both in vivo animal models and human studies in aging have shown that various nutraceuticals have a beneficial role in the promotion of positive mental health and well-being in aging, prevention of cognitive decline and eventually dementia, as well as slowing down the benign cognitive decline associated with normal aging [40, 41, 42]. Few nutraceuticals that were found to be useful in this regard are:

Brahmi herb (Bacopa monnieri): enhances cognitive performance in attention and logical memory domains and prevents and improves depressive symptoms.

Ashwagandha (Withania somnifera): enhances memory and sleep in aging and improves attention, executive functions, and information processing.

Turmeric (Curcuma longa): increases brain-derived neurotrophic factor (BDNF), prevents AD and depression.

Garlic (Allium sativum): reverses the levels of stress-related hormones and improves learning and memory.

Pumpkin seeds (Cucurbita maxima): improves memory and reduces depression [40].

Other nutraceuticals, including multivitamins, minerals such as zinc, selenium, and magnesium, fish oils, etc., also help in the improvement of cognitive functions in various domains [40, 43, 44, 45, 46, 47].

2.1.2 Role of nutraceuticals in other neurocognitive disorders

Most studies on the nutraceuticals’ efficacy on neurocognitive disorders have focused on Alzheimer’s disease. However, few studies have looked into the role of nutraceuticals in other neurocognitive disorders as well [39]. These studies are less robust and ambiguous in conclusive clinical implications.

In Parkinson’s disease, nutraceuticals are found to be beneficial either by reducing the dose of L-dopa required or by acting independently, thus reducing the symptom severity [48]. In vivo studies have shown that vitamin B complex, vitamin D, creatine, fish oils, curcuminoids, mucuna seed powder extract, resveratrol, quercetin, Ginkgo biloba, etc., are beneficial in reducing the severity of motor symptoms, preventing the nonmotor symptoms and cognitive symptoms associated with PD [49, 50].

In vascular dementia (VD), the B vitamin complexes especially vitamins B6, B9, and B12 are found to be useful in preventing its occurrence [51]. Various Chinese herbal preparations, such as Ginkgo, Huperzia, curcumins, Ginseng, Brahmi, saffron, green tea, etc., found to be helpful as adjuvants for the pharmacological treatment of cognitive decline in VD [52]. The complex herbal formulations that include these herbal products in various combinations were found to be superior to the individual preparation [53, 54].

In patients with stroke and post-stroke sequelae, nutraceuticals are found to be clinically beneficial at various stages. They reduce the risk of occurrence of stroke and can be used as prophylactic agents to promote ischemic tolerance to delay, prevent, or postpone the occurrence or reoccurrence of stroke. They can also be used as adjunct therapeutic agents to minimize secondary brain damage in the case of acute stroke [55, 56]. Clinical studies have shown that vitamin B complex, vitamin E, magnesium, omega-3 fatty acids, polyphenols, and clinical studies have shown that coenzyme Q10, cystine, L-glutamate, retinoic acid, capsaicin, and vitamin D3 are useful as prophylactic agents. Nutraceuticals, including vitamin cocktail, minerals such as zinc and selenium, and curcumin, are used as therapeutic adjuvant agents in acute stroke for early recovery and prevention of complications [51, 56].

In Huntington’s disease (HD), there are very few nutraceutical compounds that are found to be helpful. These include amino-oxy acetic acid (AOAA), levocarnitine [57], curcumin, taurine, resveratrol, anthocyanins, and quercetin [58]. Souvenaid™, a medical food composed of uridine monophosphate, DHA, choline, EPA, selenium, folic acid, phospholipids, and B vitamins has been found to have a significant positive impact on the behavioral symptomatology and theory of mind (ToM) skills in patients with frontotemporal dementia (FTD) [59].

2.1.3 Molecular mechanism of action of nutraceuticals in invertebrate models

Age is the major risk factor for various neurocognitive disorders [2]. There has been significant progress in elucidating the molecular mechanisms of aging [60, 61]. A number of genetic factors called longevity-related genes have been identified to modulate lifespan and health span in model organisms ranging from yeast, worms, flies, and rodents [62]. These genes fall into three nutrient sensing pathways:

• Target of rapamycin (TOR): sense cellular amino acid levels

• Insulin/IGF-1 like signaling (IIS): sense glucose levels

• Sirtuin pathway: sense NAD+ or NAD+/NADH levels

Nutraceuticals bind to the proteins that are translated from these genes, which will either inhibit or stimulate the further downward molecular pathway, leading finally to longevity and increased health span (Figure 3).

Figure 3.

Schematic representation of nutrient signaling, and stress response pathways associated with aging and longevity in C. elegans and D. melanogaster [62]. ROS: Reactive oxygen species, SIR: Sirtuin, OSR: Osmotic stress resistant, MAPK: Mitogen activated protein kinase, UNC: Calcium/calmodulin dependent protein kinase, TOR: Target of rapamycin, SKN: Gene for protein skinhead-1, IIS: Insulin/IGF-1 like signaling, DAF: Gene for FOXO protein, HSF: Heat shock transcription factor.

2.1.4 Interaction between nutraceuticals and the gut microbiota

The gut microbiota is a collection of colonies of multiple microbes that reside in the body and live in a symbiotic relationship with their host [63]. The brain-gut-microbiota axis comprises a part of this microbiota that is an extensive communication network between the brain [64] and gut. This axis plays an important role in the emotional and cognitive development of an individual, and any dysbiosis in this axis will lead to the occurrence of neuropsychiatric illnesses [65, 66]. Recent studies have shown the interaction between hypothalamo-pituitary–adrenal (HPA) axis and brain-gut-microbiota axis in the causation of psychiatric disorders [63].

Probiotics are various bacterial strains that exert beneficial effects through the number of ways such as antimicrobial effects, modulating the host’s immune response, enhancing the functioning of epithelial barrier [63, 67]. The recent studies at the preliminary stage have shown that nutraceuticals, including prebiotics (fructo-oligosaccharides, xylo-oligosaccharides, and inulins), anthraquinones, phytoestrogens, polyphenols, amino acids, vitamins, and omega-3 fatty acids, can interact with gut microbiota, often improving the diversity of gut microbiota, regulating immune function of the host, and improving the integrity of the intestinal barrier, which may have a beneficial role in the prevention and treatment of various neuropsychiatric and neurocognitive disorders [68, 69, 70, 71].

3. Evidence based on nutraceuticals in neurocognitive disorders and healthy aging

There are a number of studies that have investigated the efficacy of nutraceuticals in the prevention and treatment of neurocognitive disorders. These studies vary from each other in terms of methodology, sampling size and strategies, study design, duration of treatment, and selection and doses of various nutraceuticals [72]. The results of all these studies are largely mixed. Therefore, these studies need to be replicated in larger representative samples for better quality of results and translation into routine clinical practice [73]. The lack of adequate blinding, placebo response, mixed population, and clinical pragmatism limit the interpretation of these results. Hence, it is difficult to draw clinical implications. The overview of some of the studies has been depicted in Table 2.

Study	Study type	Sample characteristics	Intervention	Study duration	Results
de Jager et al. [74]	Double blind single-centre randomized controlled trial	Diagnosis-MCI n = 266 (intervention = 133, control = 133) mean age = 76.8 years	0.8 mg folic acid +0.5 mg vitamin B12 + 20 mg vitamin B6	2 years	Intervention group performed significantly well in memory tasks
Krikorian et al. [75]	Randomized placebo-controlled double blind trial	Diagnosis-MCI, n = 12 (intervention = 5, control = 7), mean age = 72.8 years	6–9 ml/kg of concord grape juice	12 weeks	Intervention group performed significantly well in memory tasks
Bo et al. [76]	Double blind randomized placebo-controlled trial	Diagnosis-MCI, n = 86 (intervention = 44, placebo = 42), mean age = 71 years	625 mg DHA + 600 mg EPA twice daily	6 months	Intervention group performed better in perceptual speed, visual memory, and working memory tasks
DeKosky et al. [77]	Double blind randomized placebo-controlled trial	Diagnosis-MCI, n = 482 (intervention = 256, control = 226) mean age = 79.1 years	120 mg of Gingko biloba extract twice daily	6.1 years	No significant effect in either the incidence of dementia or AD incidence
Peterson et al. [78]	Double blind randomized placebo-controlled trial	n = 769 (intervention = 257, donepezil group = 253, placebo = 259), mean age = 72.9 years	2000 IU of vitamin E daily v/s donepezil v/s placebo	3 years	There were no significant differences in the rate of progression to Alzheimer’s disease between the vitamin E and placebo groups at any point.
Desideri et al. [79]	Double blind randomized parallel arm study	Diagnosis- MCI n = 90 (high v/s intermediate v/s low- 30 each) mean age = 71.2 years	Flavanol dose: High (990 mg/day) v/s intermediate (520 mg/day) v/s low (45 mg/day)	8 weeks	High dose flavanol group performed significantly well in executive function, processing speed, and verbal fluency
Ringman et al. [80]	Double blind randomized placebo-controlled study	Diagnosis- AD; n = 36 mean age = 73.5 years	Curcumin dose 2–4 gram/day	24 weeks	Curcumin was generally well tolerated, but no significant benefits in AD in various cognitive tasks
Shults CW et al. [81]	Observational study	Diagnosis- Parkinson’s disease (PD)	—	—	Levels of coenzyme Q10 in mitochondria was significantly lower in PD patients than controls
Evans et al. [82]	Randomized placebo-controlled trail	Study group- post menopausal women n = 80	Trans-resveratrol 150 mg/day	14 weeks	Resveratrol group did significantly better in cognitive tests such as verbal memory and overall cognitive performance
Tomata et al. [83]	Prospective cohort study	n = 13,988	3 arms: green tea consumption 1–2 cups /day v/s 3–4 cups/day v/s 5 or more cups/day	3 years	Green tea consumption is significantly associated with a lower risk of incident functional disability, even after adjustment for possible confounding factors.

Table 2.

An overview of few trials of nutraceuticals on various neurocognitive disorders, MCI, and healthy aging.

4. Clinical utilities and advantages of nutraceuticals

Recently, there have been various small- and medium-size studies looking into the efficacy of nutraceuticals in the promotion of healthy aging, prevention of dementia in MCI subjects, and slowing down the progression of cognitive deficits in various neurocognitive disorders. In comparison with the pharmacological drugs that are being used for dementia, nutraceuticals bear many advantages:

• They are naturally occurring substances and are easily available in varieties of dietary constituents and formulae [84].

• The manufactured nutraceuticals may be easily available and procured from provisional stores or pharmacy counters as over-the-counter medications [85].

• Most of the nutraceuticals are taken orally, are easy to use, and are generally more acceptable.

• The preliminary trials have shown that these agents are safer to use in humans and will not cause any significant adverse effects [15, 17].

• In the current times of apparent therapeutic nihilism in the health professionals with regard to the pharmacological treatment options for neurocognitive disorders owing to the stagnation of new drug development, nutraceuticals may come handy in this respect [20].

• There is substantial scientific evidence on the mechanism of action of nutraceuticals through the studies in animal models [39, 62].

• The studies on pharmacodynamics and pharmacokinetic aspects of nutraceuticals in human subjects are going on.

• Any given nutraceutical may have multiple health benefits, such as the prevention and treatment of many chronic diseases such as diabetes, hypertension, heart diseases, atherosclerosis, musculoskeletal diseases, cancers, etc., along with neurocognitive disorders [85].

• Along with treatment aspects, nutraceuticals have a beneficial role in general health and well-being, healthy aging, and prevention and slowing down frailty in the elderly.

• Nutraceuticals may be well accepted by the general population and patients as they are naturally occurring, culturally ingrained in the given society, and devoid of the stigma associated with taking “artificial” medications.

5. Challenges and controversies of using nutraceuticals in clinical practice of dementia and healthy aging

The use of nutraceuticals is not free from challenges. These range from the point of production to the point of consumption and its effects on the human body as well as lack of a sound evidence base. Especially, when it comes to the aging spectrum, it is challenging to set arbitrary standpoints to assess cognitive status and effects of nutraceuticals. Another age-old challenge is the lack of standardized socioculturally sensitive cognitive assessment tools. Nutraceuticals are widely available in food products and often used over-the-counter; hence, the dose–response relationship is often obscure. Various caveats while discussing the role of nutraceuticals in healthy aging and neurocognitive disorders are the following:

• The results of interventional studies on the nutraceutical on various neurocognitive disorders are mixed across the board, and there is no emphatic evidence to support the use of nutraceuticals in these disorders [20].

• These studies have shown a marked placebo effect while treating patients with dementia and also in healthy aging [86].

• The ideal approach would be combining the nutrients together to match the physiological requirement of the body, which may be challenging, and manufacturing the complex mixture of various nutraceutical formulations may be cumbersome and costly [87]. It also makes it difficult to assess the efficacy of each constituent.

• There are challenges in analyzing the large data pertaining to the proportion of compositions of nutraceutical constituents in the food and assessing their qualities [88].

• The available questionnaires and rating scales on diet and nutritional intake for monitoring of the effects of nutraceuticals are prone to recall bias and may have confounding effects on the study results [20].

• Testing the baseline nutrient levels of the nutraceuticals in the body and personalized medicine and a more targeted approach by prescribing the nutraceuticals based on specific nutritional deficiencies is required in the current scenario of precision medicine practice [87].

• The setting of an appropriate dosing regimen may be difficult due to erratic patterns of metabolism, poor blood–brain barrier penetration, nonspecific targeting, and reduced bioavailability.

• Neurocognitive disorders are common in older people. Old age is associated with changes in pharmacodynamics and pharmacodynamics that can influence the bioavailability, metabolism, and, eventually, the action of all drugs. Adverse effects of medicines and toxicity are, hence, more frequent [2, 3, 7]. In addition, the central nervous system is more vulnerable to the effects of any drug in dementia, and dosing needs supervision as functional capacity declines gradually with dementia progression. Without standard guidelines, it becomes difficult to decide appropriate dosing regimen for nutraceuticals in older people (especially in those living with dementia), which is safe and well tolerated [84, 85]. More research is warranted to understand the safety of ingestion of nutraceutical-based products in old age. Another related concern is drug–drug interactions as polypharmacy is a rule rather than exception in later life.

• There is a lack of standardized treatment guidelines for the use of nutraceuticals [21, 56]. This leads to wide variation and subjectivity in their dosing and usage.

• Further studies are required to look into the pharmacokinetic and pharmacodynamic profile of nutraceuticals specifically in humans [21].

• There is a need for robust evidence for the regulated regimens of nutraceutical prescription including dose, duration, and knowledge of adverse reactions with post-marketing surveillance.

• The nutrient mixtures are not free from various contaminants, such as allergens, natural and unintended contaminants, heavy metals, pesticides and herbicides, mycotoxins, natural plant toxins, microbiological agents, marine toxins, etc., which can be harmful to humans and need to be purified before marketing [85].

• The potential interactions of nutraceuticals with other drugs and supplements need to be studied.

• The long-term impact of continued nutraceutical intake needs to be studied [84].

• As most of the nutraceuticals are available as over-the-counter supplements, there is a risk of abuse and toxicity [63].

• Inertia among clinicians regarding their use, misinterpretation of their role as “placebo,” which is further perpetuated by the lack of strong evidence base.

• There are multiple other factors that can influence aging and the trajectory of neurocognitive disorders (such as age, gender, substance use, education status, cognitive and leisure-time activities, exercise, diet patterns, social connectivity, sleep, relationships, and stress levels). Many trials involving nutraceuticals either do not take these factors into account or are too stringent about inclusion criteria, which makes the study population nonrepresentative of clinical settings [73, 87]. This makes the findings difficult to interpret. The complex interplay between all these modifiable and nonmodifiable factors in aging can potentially modify the influence of nutraceuticals, which needs further research.

• There is a need for the development, implementation, and evaluation of public health strategies for improving nutrition in the general population [21].

6. Conclusion and future direction

Nutraceuticals are naturally derived bioactive compounds that are found in foods, dietary supplements, and herbal products and have health promoting, disease preventing, or medicinal properties. They have multiple actions, including anti-inflammatory, antioxidant, anticarcinogenic, and antimicrobial properties. The field of nutraceutical psychiatry is relatively new and is slowly seeping into the mainstream psychiatric practice because of a number of recent studies that have established some efficacy in the prevention and treatment of neurocognitive disorders, slowing the progression of MCI into dementia and promotion of healthy aging. However, these studies are significantly heterogeneous in terms of methodology, sample selection, assessment, and dose and formulations of nutraceuticals with largely mixed results. We are lacking robust scientific evidence for the efficacy of nutraceuticals in cognitive neurology and psychiatry. Till date, nutraceuticals continue to be used as adjuvants or over-the-counter products for healthy aging as well as the prevention and management of dementia.

We need more large-sized randomized controlled trials for the better establishment of the efficacy of the nutraceuticals in neurocognitive disorders. The molecular basis of the action of nutraceuticals in human subjects needs to be unraveled for a better understanding of these molecules. The composition of each supplement must be carefully studied, and there has to be a rigorous regulatory mechanism for dosing, purification, mixing the different compounds, manufacturing, prescription, and marketing of these compounds that are backed by scientific evidence. Further studies are required for personalized medicine based on the physiological requirement of the body after testing for the blood levels of the nutraceuticals. From a public health perspective, the public and the health professionals need to be educated regarding the healthy nutrition and the availability of various nutraceuticals, and the policies pertaining to the regulation of sales of these compounds need to be formulated. Notwithstanding all limitations, nutraceuticals hold an immense promise in the field of healthy aging and disorders related to age. A deeper understanding of the nuances related to the mechanism of action, dosage, composition, role in different time periods of life, and, finally, other physiological effects will improvise their role in preventive and aging medicine. Age-appropriate guidelines can then be put into practice to help clinicians worldwide with their use. Whether nutraceuticals work in neurodegenerative conditions, especially dementia, stands the test of time, but based on the available evidence, it is definitely worth a try!

Conflict of interest

None.

Author contributions

Both the authors have contributed equally to the conceptualization, design, literature review, drafting and editing the manuscript. The final version has been agreed upon by both the authors.

Funding

None to disclose.