Nutrigenetic-based supplementation and perceived wellness: a single-blinded, randomized, crossover pilot intervention study on Romanian healthy adults

Introduction

Decades of nutrition research have shown adequately that food intake may contribute to the prevention of various chronic illnesses^(1,2). While standard nutritional recommendations target all individuals, more recently, concepts such as precision nutrition and personalized nutritional targets aim to particularize such needs according to individual characteristics^(1,3,4).

Macronutrients are responsible for providing the energy and building blocks the human body needs, but their ratios may vary greatly. If needed, the body can compensate for short periods the insufficient intake of one type of macronutrient. On the other hand, micronutrients in foods are found in small amounts and have essential roles in metabolism. Deficiencies in the micronutrient supply cannot be compensated and, therefore, they impact the human body’s homeostasis and its normal functioning^(2,5,6).

A balanced and varied diet ensures, to a certain extent, the needed amount of micronutrients⁽⁵⁾. Regulatory bodies in the field of nutrition, from US (USDA; The United States Department of Agriculture) and Europe (EFSA; The European Food Safety Authority), established terms that describe the needed amount of nutrients, such as RDA (recommended dietary allowance), PRI (population reference intake), AI (adequate intake) and others, as well as standardized values or intervals that are suitable for the majority of the population^(2,5,7,8).

The recommended daily intake values for micronutrients are estimated to ensure a good health status in the population, and if these are not met, then food supplementation is proposed^(5,6). Most food supplements include vitamins, minerals, essential amino acids and fatty acids, but also plant extracts or live bacteria (e.g., probiotics)⁽⁶⁾.

When designing a personalized nutrition plan, various factors are taken into consideration, such as health status, genetic data, microbiota, metabolism, circadian rhythm etc., along with environmental and social factors^(1,3). In this way, additional benefits are added in preventing disease and improving health⁽³⁾.

A new kind of medical information, that impacts precision nutrition, emerged as a result of technological progress and genetic advancements, which aims to explain the individual characteristics in response to food^(3,6). Nutrigenetic testing detects genetic variations that have a role in disease development, specific nutrient metabolization pathways, the efficiency of energy consumption and micronutrient intakes etc., and are the basis of highly specific individual recommendations concerning diet and lifestyle^(6,9,10,11). These tests have become more and more popular and accessible to the general population⁽¹⁰⁾.

Individuals carrying specific genetic variations may present an increased risk for certain diseases if their diet is not adequately adapted^(3,9). In some genes that are strongly associated with nutrients metabolism, genetic variations could influence dietary requirements, and this may impact the health status of each individual⁽⁹⁾. As an example, in Europe, over 27.8 million people of 55 years of age and above are diagnosed with osteoporosis, with more than 1.2 million fractures that are disease-related. It is estimated, based on the published data, that calcium and vitamin D supplementation, following personalized nutrition plans, could decrease the number of fractures by 186,690 every year, which is equivalent to savings of more than 4 billion euros in healthcare costs⁽¹²⁾. 

Thus, precision nutrition, including nutrigenetic testing, could prove beneficial against disease-related outcomes^(3,4,6,9).

As part of a bigger study, we report here ancillary data that investigated the subjective impact of a nutrigenetic-based nutritional intervention upon the preferences of participants, as compared with an intervention based on standard EFSA recommendations.

Methodology

The present study was approved by the Ethical Review Board of Shape Divine Center and registered at ClinicalTrials.gov (NCT05342766). Prior to the beginning of the study, the informed consent was obtained from all recruited subjects. Forty-six healthy adults (males and females, between 18 and 60 years old) were recruited from the Bucharest metropolitan area (Romania). They were randomly assigned to two equal groups (A and B; n=23 each). The study followed a single-blind, crossover experiment design, and it spanned over nine months, divided into three equal periods. To securely process data and results, as well as to ensure personal data confidentiality, the participants were anonymized and were randomly assigned a number from 1 to 46. The successful randomization between groups by sex and age was tested using the Student T test, with p values well over 0.05.

The participants (n=46) were initially tested to determine the individual genetic variations in genes responsible for interacting with the intake and assimilation of foods (nutrigenetic testing), using the Advanced NGx test (Advanced Nutrigenomics, Durham, North Carolina, USA). Serum levels for the following fatty acids, vitamins and minerals were measured: ALA (alpha-linolenic acid), LA (linoleic acid), vitamin A, vitamin D, vitamin E, vitamin K, vitamin C, riboflavin, niacin, folates, vitamin B12, calcium, magnesium, selenium, and zinc.

The subjects’ food intakes were collected at baseline by using seven-day dietary journals, in which each participant noted the type, description, quantity and hour of the day each food or drink had been consumed. Then, the 24-hour average nutrient intakes were estimated after introducing the journal data in the Food Tracker web-based calculation module, available at https://www.nutritionvalue.org/. These intakes were used for further comparisons and calculations for dietary interventions. Based on the first set of blood tests and the nutrigenetic test results, micronutrient deficient intakes were noted and further supplemented as described in the study below. Also, during interventions, the study team evaluated the dietary intakes, and the supplements use through 24-hours dietary recalls⁽¹³⁾. 

Each group received two interventions (“nutrigenetic” and “standard”) of three months each, spaced out by a washout period of three months, as described below. Participants in Group A underwent a nutri­tion intervention (the first three months), where the differences between actual intakes and the recommended ones, guided by the nutrigenetic test results, were provided in the form of dietary supplements. At the same time, the participants in Group B received a standard type of intervention, in which the dietary supplements were given according to the EFSA (European Food Safety Authority) general recommendations, from which the actual intakes were subtracted. Thus, each subject received a daily number of capsules and/or tablets, containing only those nutrient amounts needed to compensate for the deficient intakes, calculated as the difference between the recommended intakes (nutrigenetic or EFSA, respectively) and the actual intakes as estimated by the dietary journals. In the study, the participants were strongly advised to continue with their usual dietary patterns, as no other dietary intervention was required except for individualized supplementation.

At the end of the first intervention, subjects were tested for serum levels of the same nutrients described before. The first intervention was followed by a three-month washout period meant to clear the effects of the first intervention in both groups. During this time, the participants were instructed to continue their usual dietary patterns, as no supplementation was required.

The second intervention started with a new set of blood tests, in order to document the levels of nutrients of interest at the end of the washout period. Then, both groups received the same two interventions, but in a reverse order: the nutrigenetic-based supplementation plan was implemented for the participants in Group B, while the EFSA-based supplementation was implemented for the subjects in Group A. The study concluded with a last set of blood tests, at the end of the last interventional phase. In total, four sets of blood tests were collected and further processed in this study. 

The study team designed individualized nutritional plans for the daily administration of dietary supplements. At the beginning of each intervention, every participant received the accurate number of capsules and tablets, along with directions to use (e.g., fat-soluble vitamins to be taken with meals, as well as omega-3-containing supplements). The compliance was measured by counting the number of capsules and tablets that remained unused at the end of each intervention. A criterion of minimal compliance of at least 80% was deemed necessary for the participants to complete the study successfully.

At the end of the study, while still blinded to the interventions received, each participant was asked to indicate which intervention (either the first or the second) he or she preferred, given the perceived state of wellness associated with either of the interventions. The participants based their responses on the subjective self-assessment of their overall state of health, psychological state, and fitness. Most participants indicated only one intervention, while few indicated both interventions. For those who indicated both interventions, each of the interventions was added to the pool of responses. Therefore, the number of responses was slightly higher than the number of participants. Of the 46 initial participants, three were excluded due to noncompliance.

The statistical calculations were performed using JASP 0.18.1.0 software⁽¹⁴⁾. The difference between the preferences for the standard versus the nutrigenetic intervention was assessed using a binomial test. The order effect was tested using Fisher exact test.

The subjects participated in this research without any financial incentive.

Results

The statistics of participants’ preferences (Figure 1) indicated that 65.5% of them selected the nutrigenetic-based intervention, while the rest of them (34.5%) selected the standard intervention as their first choice (binomial testing; p=0.025). The number of participants (n=43) was too low to test for differences by sex.
 

To assess whether the order of interventions (order effect) had any influence, Fisher’s exact test indicated no order effect bias (p>0.05; data not shown).

Discussion

This study revealed that 65.5% of the participants preferred the nutrigenetic-based micronutrient supplementation, as opposed to an intervention based on standard EFSA recommendations, according to their perceived state of well-being during the interventions. This result was not influenced by the potential bias induced by the order effect, as indicated in the results section.

Previous studies have shown that the use of nutrigenetic testing in designing nutrition interventions could be useful regarding compliance and behavioral changes needed to achieve the sought outcomes^(15-17). However, a more rigorous scrutiny of the role of nutrigenetic testing in behavioral changes concerning nutrition revealed that no definitive conclusion can be made about its usefulness⁽¹⁸⁾ and, if anything, such changes were present in a small percentage of nutrigenetic test users⁽¹⁹⁾. Therefore, whether nutrigenetic testing is helpful or not in driving nutrition-related behavioral changes is a subject that needs further research. This study is the first one – to our knowledge – that assessed the subjective preferences of an intervention based on micronutrient supplementation that was designed using nutrigenetic testing.

Little is known about the roles that nutrigenetic testing has in the nutritional practice in Romania. Only one study has been published to this date, indicating that nutrigenetic-based diets could bring some benefits. However, the study was neither randomized, nor blinded, and it consisted of a collection of cases⁽²⁰⁾. The present nutrigenetics study is the first randomized and single-blinded one, to our knowledge, that was performed on Romanian participants.

This study has important limitations. The small number of participants did not allow us to infer any additional conclusions, and it needs further validation in more representative cohorts. As our participants were healthy adults, inference cannot be made for other groups (children, individuals with chronic diseases etc.). The indication of a certain preference towards a nutrigenetic-based supplementation may not be construed as indicating the efficacy of such an intervention as compared to other dietary approaches. Also, because the structure of nutrigenetic tests is widely different, no conclusions can be made for the use of other tests than the one employed in our study.  

This study was supported by funds contracted to Shape Divine S.R.L. (Bucharest, Romania), by Smart EpigenetX S.R.L. (Braşov, Romania) from a grant financed through the 2014-2020 Regional Operational Program (REGIO), investment priority 1.1C - 2020 Call - Precision Nutrition project, SMIS code 150548.

Corresponding author: Mihai Niculescu E-mail: mihai.niculescu@gmail.com

CONFLICT OF INTEREST: none declared.

This work is permanently accessible online free of charge and published under the CC-BY.