The human diet requires both macronutrients, including carbohydrates, proteins, and fats, and micronutrients, such as vitamins and minerals. While macronutrients provide the main source of calories, micronutrients are required for developmental processes. Even though they are only required in a small amount, they have a profound impact on health and are vital to body development, disease prevention, immune function, tissue regeneration, and optimizing health (1, 2).

Micronutrient supplementation has gained popularity among individuals who want to ensure and maintain their health and wellness. Consumed by 50% of adults and one-third of children in economically advanced economies, the dietary supplement business is worth more than US$100 billion annually (3). According to the National Health and Nutrition Examination Survey (NHANES) collected between 1999 and 2014, the prevalence of any supplement use has significantly increased from 52 to 58%, whereas that of vitamin and mineral use has increased from 47 to 52% and from 47 to 51%, respectively (4). The trend of any supplement use varied by age, sex, race/ethnicity, or education but not by diabetes duration or comorbidities associated with diabetes. During 2017–2018, 57.6% of adults of at least 20 years of age reported that they had taken a dietary supplement within the past 30 days; individuals with a higher family income were more likely to consume a dietary supplement than those with a lower family income (4). Furthermore, women were significantly more likely than men to use a dietary supplement overall (63.8 vs. 50.8%) (4).

In contrast to mono-substance supplements, supplementation of multiple vitamins and minerals has significantly decreased from 36 to 32%, largely because micronutrient supplements are often manufactured in numerous single-substance capsules, which can decrease compliance. Multi-vitamin multi-mineral (MVMM) supplements, which contain numerous vitamins and minerals within one single-substance capsule, alleviate the issue of non-compliance by making it easier for consumers to supplement with multiple vitamins and minerals. However, attempts to mix several vitamins and minerals into one MVMM product have been both legally and technically complicated. Each MVMM “recipe” must be registered with the national authority of the country, such as the Food and Drug Administration (FDA) (5). Furthermore, product variation of available MVMM supplements, including varying product formulations, has led to limited evidence on the efficacy of different forms of MVMM supplements. It has been suggested that different MVMM formulations could also impact the degree of nutrient absorption in the body. There is some evidence to suggest that vitamin D buccal spray, for instance, has higher absorption than soft gel capsules (6). However, the lack of evidence looking at the formulation of MVMM supplementation and its effects on laboratory parameters makes it difficult to understand the extent to which MVMM formulation impacts its efficacy. Thus, the objective of this study is to comparatively investigate the effectiveness of different formulations of combined MVMM products, specifically Hydro-Cell-Key (HCK) granules vs. VTL-7 capsules, and their impacts on certain laboratory parameters, including serum micronutrient levels and quality of life (QOL) (focusing on the vitality domain).

A hospital with a qualified production facility might procure raw substances and produce an MVMM product that does not require FDA approval for in-house use. With this in mind, Vital-Life Scientific Wellness Center (VSWC), i.e., a medical anti-aging and wellness center in Bangkok, Thailand, developed an in-house personalized vital-life (VTL-7) MVMM capsules. As several patients preferred fewer capsules per day, along with an absorption concern, VSWC considered switching from capsule to granule formulation. To compare the efficacy of a similar MVMM product in granule formulation, the HCK®, i.e., MVMM granules of the Hepart AG Switzerland group, was included in the study. The HCK granule contains vitamin D3, vitamin C, vitamin E, vitamin A, coenzyme Q10, carotenoids, and flavonoids; hence, it was determined to be one of the best available candidates in comparison with the VTL-7 capsules. Built into a plant hydrocolloid matrix, the vitamins and minerals in granules are released in the intestines through the colloid film formed by the colloidal system after ingestion. This process mimics the absorption of micronutrients from natural fruits and vegetables, resulting in optimal nutrient distribution throughout the body, along with prolonged absorption over several hours, prevention of disturbances, and antagonism of various micronutrients. However, the formation of a dry granulation requires many more steps than capsule formulation.

The clinical efficacy (i.e., serum level of the micronutrients) of the original HCK® granules has been anticipated to be higher than conventional capsule formulation; however, there has been no comparative evidence of the changes in blood vitamins and minerals between the two products. As previously mentioned, product formulation could affect not only individual compliance but also laboratory changes. Thus, the methods used to examine both the effects of MVMM supplementation and the relationship between MVMM product formulation on laboratory parameters and QOL are presented in this study.

Absorption of micronutrients could be affected by several factors such as variants of genetic polymorphisms, underlying health conditions, diet, exercise, smoking, alcohol consumption, age, and form of supplements (9). This quasi-experimental study revealed a comparably significant increase in serum levels of two out of the six micronutrients that were provided to the participants as supplements in two different oral formulations. The significant increase in only two out of the six micronutrients could be due to various reasons, including dose intake of these nutrients or individual absorption capabilities. Further and longer studies are needed to assess the reasoning behind a lack of significant increase among the other four micronutrients observed in this study.

The difference in laboratory results (vitamin D and beta carotene levels) between the study groups could be since vitamin D and beta carotenoid differed between the two products' formulations, representing two common types of Solid Oral Dosage Form (SODF). Some key differences among the differently formulated micronutrients include variations in the physicochemical state of the vitamin D (molecular forms, potency, and their physiological linkages), the complexity of the food matrix (the amount and type of fatty acids, dietary fibers, and presence/absence of vitamin D enhancer and inhibitor), and its interaction of other fat-soluble compounds with vitamin D, as well as the host-associated factors (e.g., age, disease, surgery, obesity, and genetic variation) (10). The homeostasis of vitamin C is influenced by several factors, including genetic polymorphisms and environmental and lifestyle factors, such as smoking and diet, as well as the presence of diseases (11). Excessive chronic alcohol intake is generally associated with vitamin deficiency (especially folate, thiamine, and vitamin B6) due to malnutrition, malabsorption, and ethanol toxicity. The effects of moderate alcohol use are mainly explained by a lower vitamin intake. In the case of vitamin A and beta-carotene, the effects on post-absorptive (lipoprotein) metabolism have been demonstrated (12).

Besides the effects of vitamins and minerals on blood biomarkers, previous studies showed that supplementation of multivitamin and mineral preparations has beneficial effects on mood and stress (13–15). In addition, the association between serum level of vitamin D and self-rated health in healthy male workers was observed (16). Moreover, results from a previous study revealed that elderly participants with poor physical health status assessed by the SF-36 exhibit lower alpha-tocopherol blood concentrations (17). The formulation type of the MVMM supplement used differed with each study but included both capsule and granule formulations. None of these studies, however, looked at the difference between MVMM formulation and its effect on the QOL. Nonetheless, our findings did not suggest that supplementation of vitamins and minerals may improve the QOL.

We observed that the participants who preferred no supplement were younger than the study groups. Previous studies revealed that supplement use increased with age, with 72% of adults of 65 years or older of age reporting an increased use compared with 40% of adults of 20–39 years of age (18). Several lifestyle and behavioral factors were associated with relatively less herb and dietary supplement use in young adults (19) for various reasons. First, they might prefer improving their diet and lifestyle rather than taking an oral supplement. Second, they might have been concerned about the potential side effects of the supplement (20).

The findings presented in this article could serve to influence the future of micronutrient supplementation, particularly for those with vitamin A or vitamin D deficiency. As the results from the GEE analysis (presented in the Results section) revealed a significantly higher increase in vitamin D and β-carotenoids in VTL-7 than HCK, consumers looking for supplementation of these nutrients may benefit more from capsule formulation than granule formulation. Knowing the composition of different MVMM formulations can help us to better understand the differences in the mechanism of action through which the nutrients are absorbed, based on the formulation type. Furthermore, expanding our knowledge of the different MVMM formulations can influence what kind of supplements are prescribed by medical providers to help with vitamin and mineral deficiencies, as well as help consumers to determine over-the-counter counter supplements to purchase. Still, more research should be done in this area to further explore the differences in efficacy between the two formulations by looking at micronutrients not included in this study.

This quasi-experimental study has some limitations. First and most important is the non-randomization nature of the study. Although a random allocation of participants is usually preferred, this study was conducted in a private international hospital setting, in which the participants were healthy and did not receive financial support from a third-party payer for this type of wellness service. Second, the different product formulations, which was the primary objective of this study, could indeed introduce another bias. That is, the participants who were familiar with conventional capsules, as opposed to the new formulation, were health-conscious. Although only two formulations/products were included, the findings from this study could be suggestive of the effect of supplement formulations on the change in laboratory parameters. Finally, it was not required that subjects follow a specific diet during participation in this study and, therefore, it cannot be ascertained that the diet of the subjects did not impact the uptake of CoQ10 or vitamins into the blood. Similarly, there was no method in place to assure that subjects took their supplementation exactly as prescribed, which could also influence the laboratory outcomes. Future studies should be conducted to control these factors.

Micronutrient supplement formulation, specifically granule vs. capsule formulation, was found to impact certain laboratory outcomes but not QOL. More specifically, MVMM supplements in capsule formulation were found to increase the serum levels of some micronutrients, namely, vitamin D and β-carotenoids, to a higher extent than that of granule formulation. Nonetheless, participant adherence remains a potential confounder and should be further explored.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

The studies involving human participants were reviewed and approved by Bumrungrad International Institutional Review Board. The patients/participants provided their written informed consent to participate in this study.

AC conceived of and supervised the study. BT and PI collected and help to analyze the data. KP analyzed the data. PL and NT facilitate the data collection, data analysis, and supervised the study. KP, NJ, BT, PI, and JH drafted the manuscript. All authors read and approved the manuscript.

PI was employed by Asia Global Research Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.