The importance of nutrition for physical health and disease prevention has been well documented, and the recommendations of the Global Dietary Guidelines have been clearly defined to guide effective policies. However, what to eat, when to eat, and how to stay healthy to optimize eating patterns is actually quite complex.
Many factors can influence eating patterns, including an individual's physiological needs, illness or health status, socio-environmental and cultural factors, and biological, physiological, and psychosocial responses to dietary interventions, all need to be considered.
A variety of diets can lead to positive health outcomes, but what diet is best for an individual and how that diet changes throughout the lifespan is something that many researchers and clinicians are eager to understand.
Today, "precision nutrition" is growing rapidly, emphasizing the use of personalized information to develop nutritional recommendations and diet plans for a specific group. One of its main goals is to provide tailored dietary advice as well as the expected personalized response. While there is growing evidence to support the need for precision medicine for optimal personal health and chronic disease management, there is still some way to go before "personalised" or "precision" nutrition interventions can be scaled up.
The National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (NHLBI) convened for two days on January 11-12, 2021, and attendees discussed precision nutrition in four major chronic disease areas: 1) cardiovascular disease, 2) cognitive decline and Alzheimer's disease, 3) type 2 diabetes and impaired blood sugar regulation, and 4) diet-related cancers. The meeting also highlighted significant individual differences in dietary regulation aimed at influencing health and disease. This highlights the importance that international research places on the role of personalized nutrition in chronic diseases.
Diet is a major driver of chronic disease risk, and population-based guidance should take into account individual responses. Reducing chronic diseases through diet requires more precisely:
(a) Identify the basic nutritional needs for health and disease throughout the life cycle;
(b) consider the effects of nutrients and other food substances on metabolic, immune, inflammatory, and other physiological responses that support healthy aging;
(c) Consider healthy eating behaviors.
Since it is precision nutrition, it should be a subgroup of the population, not the entire population, that may respond in a similar way to the intake or exposure of a certain diet or food component, through which we can give more specific, targeted or effective recommendations to address a certain response indicator than at the level of a large population, which is based on the genetic characteristics, metabolic status, lifestyle, disease state or indicators of a small and specific population subgroup of chronic diseases, including intestinal microecology, etc.
This article discusses and illustrates the possibilities and challenges of reducing the risk of chronic diseases through precision nutrition, some biomarkers that can be used as precision nutrition for chronic diseases, and nutritional considerations for reducing chronic diseases. It is hoped that it will contribute to the better development of the field of precision nutrition.
What is Precision Nutrition?
Precision nutrition (personalized nutrition) is a method of tailoring dietary recommendations and nutrition plans for specific groups based on factors such as genetic characteristics, lifestyle, health status, metabolic characteristics, microbial composition, etc.
★ Each person's nutritional needs are unique
Research argues that nutritional needs are also individualized because each person's biological characteristics and environmental exposures are unique.
The goal of personalized nutrition is to provide each person with nutritional advice that best suits their individual needs, thereby promoting health, preventing disease, and improving quality of life.
Personalized nutrition advice is more effective than traditional approaches when it comes to achieving long-term lifestyle changes. This may be due to precision nutrition taking it a step further, assuming that we can provide individual dietary recommendations that are known to be beneficial to individuals, based on a quantitative understanding of the relationship between individuals, phenotypes, and food consumption.
★ Points to consider for personalized nutrition
There are three aspects to consider in terms of individualized diet or individualized nutrition: 1) individualized level, 2) individualized focus, and 3) individualized scope.
Personalized levels of nutrition
There are three levels of personalization. On the first or bottom layer, we find traditional nutritional recommendations based on general guidelines for populations divided by age and sex. This is consistent with nutritional science's traditional focus on the average response of a population to a diet or nutrient and can be considered a primary prevention intervention.
On the second level, we add a layer of personalization by adding phenotypic information about an individual's nutritional status, such as biochemical and anthropometric data.
At the third level, we aim to reach a level of personalized (or precise) nutrition, which takes into account multiple aspects such as genotype, gut microbiota or metabolome. Similar to medications, nutrients are able to interact with the physiological functions of an organism and regulate molecular mechanisms, so it has the potential to help develop personalized dietary recommendations.
The focus of personalized nutrition
Focus on personalized nutrition: biological or behavioral. In precision medicine, our goal is to understand differential responses to diet and nutrients based on characteristics such as genetics, epigenetics, and gut microbes. This level of biological understanding can also guide nutritional recommendations.
For example, a better understanding of how and which specific nutrients and non-nutrients may induce an inflammatory response in the gut when encountering specific strains of gut bacteria may be key to individual recommendations for inflammatory bowel disease. However, changing dietary patterns should include a thorough assessment of current behaviors, preferences, barriers, and goals.
A range of personalized nutrition
The last aspect of personalized nutrition is its scope. In addition to varying degrees of personalization, the scope can be to address emerging issues in public health care and disease prevention, or it can be aimed at supporting the treatment of patients.
Wellens J,et al. Pharmgenomics Pers Med.2023
Biological basis of food and nutrient requirements
Throughout human history, food has shaped the human genome in order to survive and expand populations in a variety of environmental contexts. The changing and increasingly unadaptable food ecosystem for many people has led to changes in the risk of developing chronic diseases in modern times.
✦ Food availability and composition affect human genetics and phenotype
Food availability and food composition are among the major environmental selection pressures that lead to genetic and phenotypic variation in modern humans. The genome evolves through processes such as genetic selection and random drift, which can alter the relationship between diet and disease.
Not all genes in the genome evolve at the same rate. In humans and other species, highly conserved genes often encode proteins that have essential life-sustaining functions and are largely unaffected by the external environment.
In contrast, rapidly evolving genes exhibit variations in DNA primary sequences in different populations, altering physiological functions and leading to genetic and phenotypic variation in humans. This adaptive gene has historically allowed to survive in a particular environment.
✦ Poor adaptation to changes in the food environment produces disease genes
Therefore, it is not surprising that genes involved in food, nutrition, metabolism, as well as immune function exhibit some of the highest rates of genetic evolution and consequently genetic and phenotypic variation, as human populations that survive and expand over time must adapt to the unique local food and pathogenic environment. These adaptations allow people to survive in their regional environment, but when the environment changes, including changes in the food environment resulting from the transition from a hunter-gatherer society to an agrarian society, maladaptation can occur, resulting in disease alleles.
Famine is a common phenomenon and selection pressure in human history that optimizes biological functions with the minimum dose of essential nutrients required to maintain the species. The effects of this selective pressure are observed in humans and other mammals through cell-vegetative environment interactions, where the binding affinity of essential nutrients to enzymes and transporters (Km, Kt) is highly similar in humans (usually in mammals) and preserved in a way that requires minimal change in maintaining physiological functions.
✦ Food overabundance has led to an increase in the incidence of chronic diseases
Therefore, the need for accuracy in deriving dietary reference intakes (DRIs) based on maintaining basic nutritional adequacy is even more urgent, as the need to establish population subpopulations is limited to differences in physiological needs throughout the life cycle, rather than physiological changes in healthy populations that are independent of life-cycle influences such as genetics.
There are some exceptions, such as the effect of the common methylenetetrahydrofolate reductase mutant (MTHFR C677T) on cofactor binding, resulting in higher folate required to maintain adequacy.
However, the environment in which we live has shifted from famine to food overabundance, from tackling nutritional deficiencies to addressing the rising incidence of diet-related chronic diseases, all in the context of the globalization of the food supply.
We are increasingly recognizing that there is meaningful heterogeneity in the diet-disease relationship, and there is a need to establish new approaches to dietary advice, including new methods for identifying and classifying subgroups (i.e., improving precision).
History of nutrition and food guidance
Prevention of nutrient deficiencies and subsequent nutrient deficiency-related diseases, as well as maintenance of physiological function, are the goals of the recommended intake of nutrients and other food substances (i.e., energy, fibre, macro- and micronutrients).
✦ Presentation of the Dietary Reference Intake Framework
At the end of the 90s of the 20th century, a set of recommendations covering the risk of undernutrition and overnutrition was developed, widely known as the Dietary Reference Intakes (DRI) table, as follows:
Bailey RL,et al. Annu Rev Nutr.2023
✦ There are differences in the need for essential nutrients among populations
The DRI framework first introduced the concept of precise guidance, acknowledging that there are differences in the dose-response relationship of essential nutrients in a limited number of population subgroups.
Given the low precision required to prevent nutrient deficiencies and toxic states compared to reducing chronic diseases, only a limited number of population subgroups need to be considered when establishing DRIs based on maintaining the adequacy of a particular subgroup, which is consistent with human natural history. This is because most individuals in healthy people tend to have a similar response to essential nutrient exposure, and because nutrient exposure is a single underlying cause of deficiency disease and exhibits specific symptoms throughout the population over a similar course of time in healthy people.
For example, a diet deficient in vitamin C alone can lead to early non-specific symptoms of scurvy, such as fatigue for about 4 weeks, and between 8 and 12 weeks more specific severe symptoms begin to appear, including petechiae and spiral hairs.
Excessive doses may cause toxic reactions
Similarly, toxicity at high doses often results in similar characteristics in the population, such as supraphysiologic zinc intake leading to gastrointestinal symptoms and fatigue, which may lead to copper deficiency.
Dietary reference intakes with an overall, precise and individualized approach
Bailey RL,et al. Annu Rev Nutr.2023
✦ Analysis of overall eating patterns
While the DRI framework specifically focuses on other food substances in the diet, the Dietary Guidelines for Americans (DGA) have provided food and beverage-based recommendations since 1980, with an early emphasis on specific food groups and more recently a shift to a holistic eating pattern.
The DGA aims to provide a set of evidence-based dietary recommendations to "help promote health and prevent chronic disease". Food-based approaches, particularly dietary pattern studies, broaden the scope of DGA and, in the process, represent "the quantity, proportion, variety, or combination of different foods, beverages, and nutrients in the diet, as well as their frequency". They are consumed by Xi habit".
Dietary patterns can be derived in a variety of ways, and all approaches can be classified as stand-alone or dependent on specific health outcomes. Outcome-dependent methods incorporate outcomes of interest or intermediate biomarkers into models used to derive patterns; examples include descending regression and classification, and regression tree analysis.
Although these methods can be used to examine the relationship between diet and specific outcomes, most nutrition researchers use methods that are not related to the outcome of interest to describe general diet quality.
There are two broad categories of methods for developing outcome-independent dietary patterns: data-driven techniques, such as factor analysis or cluster analysis, which emphasize data reduction techniques or clustering individuals based on reported dietary intake, and index-based methods, which are a priori patterns based on dietary guidelines or recommendations. Categorizing dietary patterns through a data-driven approach may lead researchers to make multiple subjective decisions when deriving dietary patterns, complicating comparisons of patterns in different groups or populations and reducing their utility in studies that define food-based patterns.
However, factor analysis and cluster analysis are both useful data reduction techniques to determine the underlying structure of complex data sets, as is the case with dietary exposures. The use of indices and scores essentially creates a report card about the extent to which the diet meets predefined guidelines. While there is subjectivity in the way the scoring criteria are developed, the method provides a standardized framework for comparing different studies.
There is an association between overall dietary patterns and disease risk
To this end, the 2015 Advisory Committee on Dietary Guidelines for Americans, based on a systematic review, concluded that indices and scores are the preferred methods for capturing dietary patterns and the complexity of the diet as a whole.
Various indicators and scores are present, such as the Healthy Eating Index, the Mediterranean Diet Score, and the Dietary Approach to Hypertension Control (DASH) score.
Using this framework, 2020 concluded that there is strong evidence that higher-quality dietary patterns are associated with a lower risk of all-cause mortality and cardiovascular disease, and that there is moderate evidence of dietary patterns associated with type 2 diabetes, bone health, overweight and obesity, and colorectal and breast cancer in adults.
✦ Special life stages have unique nutritional needs
A life stage approach has recently been adopted to assess the available scientific evidence, including all life stages, with particular emphasis on the unique nutritional needs of pregnancy and lactation, and infants and young children (birth to 24 months).
In addition to the recommended food patterns to follow, for the first time, other food substances related to specific life stages of public health and public health issues across all life stages, including dietary exposures, biological endpoints or disease prevalence or validated surrogate markers of disease, have been identified.
Thus, while some dietary guidelines are universal, there is a recognition of the need to expand specific recommendations to populations based on life stages – representing the first life-stage-specific, population-specific approach to public health nutrition that goes beyond DRIs.
The DGA also recognises that there are multiple potential dietary patterns that can lead to similar health outcomes, such as the Mediterranean diet or vegetarian model to prevent cardiovascular disease. The dietary patterns reviewed and included in the DGA do not represent the use of dietary supplements and significantly underestimate the nutritional exposure of half of adults and one-third of children who use dietary supplements.
Therefore, the Total Nutrient Index was developed, which includes nutrient exposures in supplements in addition to nutrient exposures in food and beverages, in combination with food and beverage-based indices to improve the comprehensiveness of the exposure classification.
Biomarkers: Precision Nutrition for Chronic Diseases
Chronic diseases such as cardiovascular disease, diabetes, cancer, and arthritis are significant causes of morbidity and mortality worldwide, and their prevalence is steadily increasing across all age groups, genders, and ethnicities.
★ Precision nutrition plays an important role in the prevention and management of chronic diseases
A growing body of evidence suggests that precision nutrition plays a vital role in the prevention and management of chronic diseases and is considered a key area of focus for health research in the next decade.
Nevertheless, one of the main challenges of precision nutrition lies in accurately and reliably assessing foods and nutrients, especially complex foods and macromolecules. In addition, there is a need to determine how these foods and nutrients affect an individual's health and disease status.
Encouragingly, there is strong evidence to support the use of biomarkers as mediating tools to effectively establish a link between precision nutrition and chronic disease. This link helps to objectively assess food consumption and precisely determine the biological effects of complex foods and ingredients.
Despite these advances, our current understanding of how precision nutrition modulates biomarkers to prevent chronic diseases with individual differences is still in its infancy. The molecular mechanisms by which key biomarkers are involved in chronic disease remain unwell elucidated, and comprehensive and extensive research efforts are needed to bridge this knowledge gap.
✦ Multiple chronic diseases have potential biomarkers
Research has identified novel potential biomarkers for a variety of chronic diseases. Among them, single substances are used as biomarkers, such as 25-hydroxyvitamin D for coronary heart disease, retinol for non-alcoholic fatty liver disease, fluorescent advanced glycation end products for type 2 diabetes, and branched-chain amino acids for moyamoya disease.
The ratio of different substances can also be used as biomarkers
In addition, the ratio of different substances has been proposed as biomarkers. Creatine to cysteine protease inhibitor C (CR/CysC) ratio and albumin to globulin ratio were found to be non-invasive biomarkers for the prognosis of chronic kidney disease and urinary cancer, respectively.
Notably, studies have found that the Cr/CysC ratio may also be a potential biomarker for osteoporosis. In addition, the identification of the geriatric nutritional risk index as a potential marker of stroke in older hypertensive patients.
The study also found that the level of phosphorus binding to albumin can be a potential marker of all-cause mortality and cardiovascular mortality. The differentially expressed genes associated with deferrotic anemia can be used as new biomarkers to identify ischemic stroke and guide therapeutic interventions.
These biomarkers provide an important theoretical basis for the prevention and management of related chronic diseases, and also help to understand the pathogenesis of various chronic diseases.
✦ Some dietary factors can improve chronic diseases
Studies have shown that dietary supplementation of functional factors such as anthocyanins, glutamine, vitamin K, and fatty acids can alleviate heart failure, hypersalt hypertension, vascular calcification, and bone mineral loss, respectively.
It is important to control the intake of functional dietary factors
However, it is important to carefully control the dose of dietary functional factors, such as excessive intake of fatty acids can lead to metabolic diseases.
Some foods have a positive effect on various chronic diseases. For example, dietary fruit intake can improve functional constipation, a plant-based diet can be used to control metabolic syndrome, specific oral nutritional supplements (ONS) to address inflammation/oxidative issues, and saffron to alleviate cardiovascular disease.
Notably, a synergistic anti-inflammatory/oxidative effect of probiotic supplements with specific oral nutritional supplements (ONS) has also been observed.
In addition, combined training, including resistance training and high-intensity interval training or moderate-intensity continuous training, is beneficial in the treatment of non-alcoholic fatty liver disease. In addition to these dietary strategies to prevent or treat chronic diseases, dietary patterns can also lead to the occurrence of some chronic diseases, such as a high-salt diet that exacerbates the intestinal aging process.
These dietary functional factors and complex foods provide effective preventive measures for the treatment of chronic diseases. However, the specific mechanisms responsible for regulating these biomarkers have not been thoroughly explored, highlighting the need for further research in this area.
Gut microbiota: a biomarker
Microbiota diversity has been implicated in improved lipid profiles, anti-inflammatory cytokines, liver enzymes, and ultimately genetic pathways, all of which are metabolic indicators of improved health.
✦ The gut microbiota influences the metabolism of the host
Abnormal gut microbiota and daily eating/fasting cycles can both affect the host's metabolism and may lead to the appearance of metabolic diseases such as obesity. Studies have found that diet and fasting cycles lead to cyclical changes in the gut microbiome, which act as a mechanism to control host metabolism.
These differences increase the diversity of the gut microbiota. Therefore, eating patterns, timing, and dietary composition are important characteristics to consider when determining the contribution of the microbiome to host physiology and metabolism.
The link between the gut and brain is very important in determining the amount of meals
Communication between the gut and the brain is essential for determining the appropriate portion size of meals and sending signals to the brain to control hunger and satiety. Mechanosensitive gastric vagal afferents (GVAs) exhibit circadian rhythmicity in response to food-related stimuli in terms of nutrient composition and chemical pathways. This allows satiety signals to occur at specific times of the day through gut-brain communication.
Therefore, the lack of circadian rhythm in the GVA axis may lead to an increase in hyperphagia and obesity. Recent studies in animals and humans have shown that the appearance of obesity is associated with reduced microbiota diversity, altered gut microbiota activity, and dispersed microbiota abundance, particularly in the phyla Bacteroidetes and Firmicutes. When Bacteroides are allowed to remain in the gut, they continue to maintain a dynamic and largely beneficial relationship with the host.
✦ Dysbiosis of the gut microbiota is associated with chronic diseases
Dysbiosis of the gut microbiota is a mediator in the emergence of a variety of human diseases. Studies have shown that the prevalence of metabolic and inflammatory diseases such as obesity, atherosclerosis, neurological disorders, and diabetes is inversely proportional to the number of bacteroides.
Similarly, Bacteroides were found to be inversely correlated with low-density lipoprotein (LDL) and triglyceride (TG) levels, and both bacteria exhibited anti-obesity responses. In a similar pattern, the loss of body weight in mice was strongly associated with an increase in members of the genus Bacteria.
✦ Beneficial effects of gut microbes on the human body
The gut microbiota is a "material factory" that influences chronobiology, metabolic sensors, inflammatory cytokines, nerve function, and the immune system.
Gut microbes consume nutrients from the diet to produce energy and metabolites. Many of these metabolites then enter the circulation, where they may undergo additional metabolism and alter the host's metabolic and nutritional status.
The gut microbiota has a beneficial effect on the human body. The main benefits are its role in maintaining the integrity of the mucosal barrier, the effects of short-chain fatty acids produced from indigestible fibers in favor of the host, including activities against obesity and diabetes, in addition to the intestinal microbiome to synthesize essential vitamins, including vitamin K, niacin, riboflavin, pyridoxine, pantothenic acid, and thiamine to protect against infection with pathogens, to strengthen the immune system, to regulate circadian rhythms, and to nerve function in the body.
✦ The metabolites produced by the intestinal flora affect host immunity and metabolism
Many metabolites produced by gut microbes enter the bloodstream and can function immediately, or they can be additionally metabolized by the host, producing bioactive chemicals that may affect the host's metabolism and tissue function.
In addition to promoting fat absorption, secondary bile acids are reabsorbed into the bloodstream and act as ligands for the host cell farnesoid X receptor (FXR) and TGR5 bile acid receptors, which have effects on immune function and energy metabolism, among other things.
Similarly, short-chain fatty acids produced by bacteria, such as acetate, butyrate, and propionate, are not only an important source of energy for the liver and intestinal epithelium, but are also capable of altering insulin secretion, immune system activity, appetite, brain function, and fatty fats.
These short-chain fatty acids affect the body's immune, hormonal, and nervous systems because they are involved in the production of cytokines, neurotransmitters, endocrine signaling, and apoptosis processes.
✦ Some bacterial metabolites are harmful to the host
At the same time, it is important to note that the effects of some bacterial metabolites on host metabolism can sometimes be detrimental.
N-nitroso compounds, ammonia, and hydrogen sulfide produced by bacteria from dietary proteins produce reactive oxygen species (ROS) and precipitate in DNA damage.
These compounds can also activate pro-inflammatory pathways. Trimethylamine-N-oxide (TMAO), the end product of dietary choline, promotes the development of atherosclerosis and is associated with cardiovascular disease (CVD), stroke, and mortality.
Therefore, these alterations in the gut microbiome have the potential to play a role in the emergence of chronic diseases such as type 2 diabetes, weight gain, cardiovascular disease, and metabolic syndrome.
Nutrition and food guidance for chronic diseases
✦ Many people suffer from chronic diseases
Today, most people suffer from one or more chronic medical conditions and related factors such as drug use can alter nutritional needs, leading to nutritional deficiencies and secondary comorbidities.
More than half are overweight or obese, and the prevalence of severe obesity has increased over the past two decades. High rates of overweight and obesity are important public health issues that also increase the risk of cardiometabolic diseases and certain types of cancer.
✦ Diseases will affect nutrient absorption and distribution, resulting in differences in demand
Disease processes are known to affect nutrient absorption, catabolism, and nutrient distribution between tissues, potentially leading to differences in the need to maintain adequate access to certain key nutrients.
The term "special nutritional requirements" refers to the nutritional requirements required to maintain adequacy in a state of disease. Chronic diseases, hereditary diseases, including pathological states such as inborn errors of metabolism, inflammation, dietary intolerances, medications, allergies, trauma, and infections, can alter deficiencies and toxicity of basic nutritional needs.
Currently, these differential requirements for other food substances are taken into account in medical nutrition therapy, a more individualized approach that is currently beyond the scope of the DRI.
The biological basis for the development of DRI aimed at reducing chronic disease does not support limiting nutrition- and food-based recommendations to apparently healthy individuals, as there are no clear diagnostic criteria for when the disease began. Chronic diseases occur and manifest throughout the lifespan and are closely related to aging and many static and dynamic factors, as well as environmental exposures, including food.
The gradual decline of biological systems is a sign of aging and the progression of chronic diseases, which begin at the earliest stages of life. Biological network and system decline leads to functional erosion or increased random behavior, resulting in increased variability/stability of network output and system behavior, resulting in incompatibility with health.
At the molecular level, for example, this can be quantified by alterations in gene expression patterns and network function due to erosion of the epigenetic landscape of the human genome. and age-related changes in plasma metabolites, some of which are biomarkers of nutritional status, as well as changes in redox potential.
✦ Lifestyle influences the occurrence and progression of chronic diseases
Many lifestyle, environmental, and intrinsic physiological risk factors can influence the rate of biological aging and the onset and progression of chronic diseases, including certain cancers, type 2 diabetes, cardiometabolic and neurodegenerative diseases, among others.
Family history (i.e., genetics) is the main immutable predictor of longevity. Chronic diseases are triggered at the earliest stages of human development through mechanisms such as genomic mutations and epigenetic programming of stem cells. In this regard, nutrient requirements can be seen as a dynamic response to slow or sustain the decline in the functional capacity of biological systems and networks required for age-related health promotion, and this is where precision nutrition efforts may be most beneficial.
A population-based approach to reducing biological aging requires better linking biomarkers of nutritional exposure, status, and function to biomarkers of disease and aging.
Reduce considerations for chronic diseases
In 2017, a framework was developed to formally incorporate chronic disease risk reduction values into the DRI. This change underscores a shift in dietary guidance to promote health and reduce the risk of chronic diseases, in addition to avoiding deficiencies.
This paradigm shift in reducing the risk of chronic disease through diet and its rationale have been published elsewhere. Unlike deficiency, most chronic diseases manifest themselves over time and are caused by the aging process and the cumulative effects of behavioral and lifestyle factors.
✦ Reducing chronic diseases requires the interplay of multiple factors to consider
As mentioned above, the establishment of food and nutrient intake recommendations to reduce chronic disease requires consideration of multiple independent and interacting factors. These additional biological factors increase population heterogeneity in the diet-disease nexus, further driving the need for more precise dietary recommendations.
Implementing precision nutrition requires knowledge and tools (e.g., biomarkers) that can quantify and link exposures (e.g., diet/nutrition, lifestyle, environmental factors, exercise) to physiological responses (e.g., metabolism, stress, immunity) to health and disease (e.g., genomic integrity, blood pressure, cognition).
It is important to note that the link between exposure and physiological response influences each other through feedback loops (e.g., diet can affect inflammation and thus dietary needs), and physiological responses interact with health, disease, and aging.
The causes and regulators of diet's relationship with chronic disease include, but far out, the role of essential nutrients in maintaining metabolism and other functions. Other food substances can be produced by:
(a) secondary pathogenic effects of essential nutrient deficiencies and excess to affect the onset and progression of chronic diseases;
(b) the pathogenic effects of unbalanced intake of essential nutrients;
(c) The causative effects of oxidative stress, immune responses and other reactions to exposure to specific food components;
(d) Ingestion of non-essential biologically active food ingredients affecting chronic disease in a manner not essential or toxic;
(e) Eating behaviors, including temporal eating patterns, also known as temporal nutrition.
Deficiencies and excesses of essential nutrients
Diseases caused by essential nutrient deficiencies and toxicity have been clinically recognized and well characterized and have historically been considered in the establishment of DRIs (Dietary Reference Intakes) with a focus on maintaining nutritional adequacy and physiological function.
When the DRI (Dietary Reference Intake) is extended to include a reduction in the risk of chronic disease, other physiological responses of the nutrient beyond its known functional role must be considered. The relationship between diet and chronic disease extends beyond physiological functions to immune and stress responses to dietary components that can reduce or increase the risk of disease.
✦ Deficiencies in essential nutrients can cause inflammation
Both deficiencies and excesses of essential nutrients can cause inflammation, and elevations of certain nutrients alter physiological processes that increase or decrease the risk of chronic disease without causing toxicity.
For example, in animal models, magnesium deficiency stimulates oxidative stress and phagocytic cells to secrete pro-inflammatory mediators, leading to chronic inflammation. In the population, dietary magnesium intake was inversely associated with cardiometabolic disease, metabolic syndrome, colorectal cancer, and serum or plasma C-reactive protein (CRP). Note: CRP is a biomarker of inflammation and a risk factor for many chronic diseases. Inflammatory mediators such as chemokines and CRPs serve as biomarkers to report aging, exercise, nutrition, and chronic diseases, including atherosclerosis, diabetes, obesity, sarcopenia, and Alzheimer's disease.
Similarly, subclinical vitamin C insufficiency is associated with inflammation, elevated plasma C-reactive protein levels, and decreased immune function.
✦ Proper nutrient levels can reduce inflammation levels
On the other hand, a high intake of essential nutrients may reduce inflammation in people with chronic diseases, provided that there is no nutrient deficiency. Vitamin D supplementation may reduce blood CRP levels and improve inflammatory markers of pediatric intestinal syndrome in overweight and obese children.
Folic acid and vitamin B12 deficiencies have been shown to exacerbate inflammation associated with disease and infection, while folic acid supplementation has been shown to lower CRP blood levels.
Overall, the role of essential nutrient deficiency or excess in oxidative stress and inflammation is not well understood. There is a need to further develop the basic knowledge of the relationship between nutrition and chronic disease, and to conduct more human clinical trials to validate the relationship between specific nutrients and chronic disease interventions. In recent years, many hospitals have opened clinical nutrition departments to promote translational nutrition interventions in the treatment and rehabilitation process.
Unbalanced intake of essential nutrients
The multifactorial etiology of the occurrence and progression of chronic diseases is characterized by the interaction between intrinsic biological systems and extrinsic environmental factors, including essential nutrients, that affect physiological functions that are essential for maintaining health.
✦ Imbalances in nutritional status can accelerate or exacerbate chronic diseases
In fact, all metabolic, signaling, and other physiological networks are involved in the interaction between multiple essential nutrients, and an imbalance in nutritional status between nutrients in the same system has been linked to accelerated or exacerbated chronic disease.
Sodium/potassium balance is associated with blood pressure as well as the risk of cardiovascular diseases and more
Sodium, potassium, and chloride play an important role as electrolytes, regulate fluid balance within cells, and play a key role in maintaining blood pressure. An imbalance in the potassium/sodium ratio in the urine reflects dietary exposure and is associated with an increased risk of hypertension and cardiovascular disease in adults, as well as morbidity in preterm infants.
While there is no association between dietary sodium intake and blood pressure in some people, some subgroups of the population are thought to be salt-sensitive and are more likely to have a negative response to higher sodium to blood pressure based on age, sex, and ancestry, as well as those with impaired renal function, obesity, and pre-existing hypertension.
An imbalance between folic acid and vitamin B12 can cause illness
The dietary ratio of sodium to potassium is critical for the effects of high blood pressure. Other minerals, as well as interactions with dietary patterns, are also associated with health.
An imbalance in the status of the B vitamins folic acid and vitamin B12 and their interaction may cause disease. Folate-mediated one-carbon metabolism is a metabolic network necessary for the synthesis of nucleotide precursors and the remethylation of homocysteine to methionine, supporting more than 100 cellular methylation reactions.
This network requires many essential micronutrients, including vitamin B12, vitamin B6, folate, niacin, and riboflavin. Elevated folate status in the setting of vitamin B12 deficiency is associated with worsening of the neurological, metabolic, and clinical manifestations of vitamin B12 deficiency alone. These potentially harmful interactions raise concerns about excessive folate intake.
These examples highlight the need to consider and recommend the range of nutritional status in a population to promote health by optimizing nutrient interactions in a given biological network and thus preventing chronic diseases, providing us with the ability to provide more precise guidance.
Immune response to food ingredients
Food intolerances and food allergies are immunological adverse reactions to food. They are common chronic inflammatory diseases whose prevalence is increasing, affecting quality of life, and are associated with a higher risk of other chronic diseases.
It is estimated that up to 20% of people exhibit gastrointestinal food intolerances.
✦ Food intolerances increase the risk of gastrointestinal diseases
There are many causes of food intolerance, including: (a) the pharmacological effects of dietary components, such as short-chain fermentable carbohydrates, also known as fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs); (b) Non-immune gluten sensitivity; They are usually administered through an elimination diet.
The most common clinical manifestation of adverse food reactions is irritable bowel syndrome, which increases the risk of gastrointestinal cancers, but adverse food reactions can also have negative effects on the skin, respiratory, nervous, and cardiovascular systems. and increase the risk of breast cancer.
✦ Different food antigens elicit unique immune responses
Food allergies are different from other forms of food intolerance, and sometimes the same dietary components can trigger multiple intolerance mechanisms. Food allergies occur when immunoglobulin E (IgE)-mediated immune response against epitopes present in specific food components occurs.
Other food antigens can also mediate immune and inflammatory responses. The data revealed increased reactivity of IgG antibodies to epitopes present in the patient's food, with the most common reactive foods being casein, milk, wheat, gliadin, egg whites, and rice, and less commonly nuts, vegetables, fish, seafood, and meat products.
Sensitivity to gliadin in gluten leads to celiac disease
For example, celiac disease is a genetically associated autoimmune enteropathy that sensitizes individuals to gliadin and glutenin in gluten present in certain grains, leading to an inflammatory response. It occurs in about 1% of the population.
On the other hand, gluten intolerance is more common, affecting up to 6% of the population, and overall, non-celiac wheat sensitivity may affect 10% of the population. Gluten intolerance is not genetic, nor does it trigger allergic reactions, but it may present with symptoms similar to celiac disease due to the activation of the innate immune system and multiple inflammatory pathways by gluten components.
✦ Adverse reactions caused by food ingredients can also have a negative impact on the gut microbiome
There are a variety of other adverse reactions to food and food composition that are independent of immune participation and manifest themselves through many different known and unknown mechanisms, which are classified as host-dependent or host-independent.
The most common clinical manifestations include urticaria or angioedema, but also asthma, gastrointestinal symptoms, hypotension, headache, and eczema. Non-immune, host-independent food intolerance involves pharmacologically active chemicals in food that affect sensitized individuals, including salicylates, vasoactive amines (such as histamine), glutamate, and caffeine, but their etiology and management remain elusive.
Nonimmune, host-dependent food intolerance typically includes a lack of host metabolic capacity, such as lactose and fructose intolerance, and nonspecific responses to certain foods, including FODMAPs. These compounds cause osmotic action in the gastrointestinal tract, promote undesirable fermentation of colonic bacteria, and can negatively affect the composition of the microbiota, trigger inflammation, and induce irritable bowel syndrome symptoms.
Bioactive Dietary Ingredients
✦ Intake of bioactive dietary ingredients may reduce the risk of chronic diseases
Intake of non-essential bioactive dietary components (also known as exogenous components) has the potential to reduce the risk of chronic disease and can therefore be assessed in the process of establishing a DI.
Carotenoids have been linked to eye health
These include bioactives such as non-provitamin A carotenoids, lutein, and zeaxanthin, which have been linked to eye health and eye development.
Flavonoids and polyphenols have antioxidant activity
Flavonoids and other polyphenols have antioxidant and transcriptional activating activity and have been linked to protection against several chronic diseases, as well as potential semi-essential nutrients such as omega-3 fatty acids.
Omega-3 intake has been linked to a variety of diseases
Omega-3 fatty acid intake has been linked to outcomes such as cardiovascular disease risk, cognitive function, depression risk, and preterm birth. However, the data supporting these associations are not consistent in the literature, which may indicate that health outcomes may be altered when different intake ranges are consumed.
✦ The health benefits of bioactive dietary ingredients vary among different populations
Since these compounds can improve health but are not technically necessary for life, greater population heterogeneity is expected for their biological and health impacts compared to changes in their historical regional abundance and different selection pressures that may play a role in essential nutrients.
In addition, the cellular concentrations of bioactive dietary components, as well as many synthetic drugs, are regulated by their catabolism. These substrates are degraded or bioactivated by cytochrome P450 enzymes, which exhibit broad differences in substrate specificity and catalytic activity within and between populations, resulting in heterogeneity in functional responses to various substrates.
Eating behaviors
There is a growing recognition that the timing and frequency of meals eaten throughout the day can affect health outcomes.
Eating time and the direct biological effects of certain other food substances, including caffeine and polyphenols, can alter the biological clock. The interaction of other food substances with circadian rhythms, fasting (including daily eating frequency), and other dietary behaviors can affect metabolic processes and contribute to the relationship between diet and disease.
✦ Understand the individual's diet and behavior patterns for accurate dietary assessment
In addition, eating behaviors exhibit inter-individual differences in physiological responses and are not currently considered to be within the scope of the DRI or DGA process, but they are an important dimension in the dietary exposure group.
Understanding not only what people eat, but also these contextual factors of eating behaviour is critical to understanding how to make accurate nutrition recommendations. Research on precision diet assessments is needed to capture these and other contextual factors to improve our ability to make more precise dietary recommendations.
Bailey RL,et al. Annu Rev Nutr.2023
Bailey RL,et al. Annu Rev Nutr.2023
Is a precision nutrition strategy possible?
An individual's response to a particular diet is the result of an interaction of metabolic, environmental, social, and genetic factors, suggesting that different individuals will respond differently to the same intervention.
For example, in a recent randomized controlled trial of more than 600 people, a 12-month low-fat diet resulted in some people losing more than 30 kilograms of weight, while others gained more than 10 kilograms, suggesting that a single diet is not working for everyone, and that precision nutrition may be more effective.
Good retention and differentiation of the diet, which may be explained by unmeasured elements such as the microbiome.
In the study, 1607 adults from seven European countries were recruited for a randomized controlled trial that provided either routine dietary advice (control) or individualized advice based on an individual's baseline diet, an individual's baseline diet plus phenotype (anthropometric and blood biomarkers) or an individual's baseline diet plus phenotype and genotype (five diet-responsive genetic variants). The results of this study suggest that personalized diets are superior to regular diets.
In this case, designing a precision diet plan for the patient may:
1) more effective in the treatment of diseases;
2) improve adherence, as personalized diets are more acceptable to patients;
3) Less restrictive.
This evidence-based research evidence is also the foundation of our business and that of related companies – collecting and organizing literature, building databases, and obtaining solutions. Then, Xi is learned from the customer's behavioral data feedback and further researched.
In addition, the causal relationship between many chronic diseases and dietary patterns is gradually becoming clear, or conversely, modern scientists, clinicians, nutritionists (usually several roles) have developed a lot of dietary patterns to deal with chronic diseases (most of the "efficacy" is far greater than drugs), the largest of which is "chronic diseases of the gastrointestinal tract", FODMAP diet, diet to eliminate food intolerance, etc., can intervene in many gastrointestinal diseases, gastrointestinal diseases are also the most rigid market.
At present, many commercial companies at home and abroad have launched personalized nutrition plans for a variety of chronic diseases, including diabetes, allergies, autoimmune problems and gastrointestinal problems.
Regardless of how data-driven, providing "a convenient and affordable way for anyone, anywhere, to advance personal care using food as medicine and enabling sustainable nutrition practices" "should be a fundamental requirement for the future of precision or personalization."
For "anyone, anywhere", "convenient and affordable, sustainable personalized health conditioning and nutrition solutions", is also the concept of our long-term pursuit of Guhe Health.
Featured References
Bailey RL, Stover PJ. Precision Nutrition: The Hype Is Exceeding the Science and Evidentiary Standards Needed to Inform Public Health Recommendations for Prevention of Chronic Disease. Annu Rev Nutr. 2023 Aug 21;43:385-407.
Rodgers GP, Collins FS. Precision Nutrition-the Answer to "What to Eat to Stay Healthy". JAMA. 2020 Aug 25; 324(8):735-736.
Demetrowitsch TJ, Schlicht K, Knappe C, Zimmermann J, Jensen-Kroll J, Pisarevskaja A, Brix F, Brandes J, Geisler C, Marinos G, Sommer F, Schulte DM, Kaleta C, Andersen V, Laudes M, Schwarz K, Waschina S. Precision Nutrition in Chronic Inflammation. Front Immunol. 2020 Nov 23;11:587895.
Zeb F, Osaili T, Obaid RS, Naja F, Radwan H, Cheikh Ismail L, Hasan H, Hashim M, Alam I, Sehar B, Faris ME. Gut Microbiota and Time-Restricted Feeding/Eating: A Targeted Biomarker and Approach in Precision Nutrition. Nutrients. 2023 Jan 4; 15(2):259.
Lee BY, Bartsch SM, Mui Y, Haidari LA, Spiker ML, Gittelsohn J. A systems approach to obesity. Nutr Rev. 2017 Jan; 75(suppl 1):94-106.
Wellens J, Vissers E, Matthys C, Vermeire S, Sabino J. Personalized Dietary Regimens for Inflammatory Bowel Disease: Current Knowledge and Future Perspectives. Pharmgenomics Pers Med. 2023 Jan 12;16:15-27.
Zhu Z, Li YL, Song S. Editorial: Biomarkers: precision nutrition in chronic diseases. Front Nutr. 2023 Jul 24;10:1257125.
Dashti HS, Scheer FAJL, Saxena R, Garaulet M. Timing of Food Intake: Identifying Contributing Factors to Design Effective Interventions. Adv Nutr. 2019 Jul 1; 10(4):606-620.