In the present study, we investigated the relationship between the pattern of AAs intake and obesity using data of 3197 men and women aged 35-70 years from Shahrekord cohort study. Factor analysis, utilizing the PCA extraction method, revealed three dominant patterns: aromatic, mixed, and alanine. The first pattern, denoted as the aromatic pattern, comprised three essential AAs—leucine, phenylalanine, and tryptophan—along with proline, glutamic acid, serine, and cysteine. The second pattern, termed the mixed pattern, was predominantly characterized by essential AAs, including lysine, threonine, methionine, isoleucine, and valine, in addition to tyrosine, aspartic acid, arginine, and glycine which exhibited positive factor loadings for this pattern. The third pattern, identified as alanine, comprised of alanine and histidine. The results of our study showed that specific AA intake patterns can be related to general or central obesity among Iranian population.
A significant inverse relationship was found between the intake of the aromatic pattern and the odds of developing central obesity. Analyses of data from a study involving 5000 adults revealed that each quartile increase in dietary intake of tryptophan, glutamic acid, aspartic acid, and proline was associated with a depressed risk of abdominal obesity (17). According to a study, the physiological functions of glutamic acid were reported as a potential therapeutic target for appetite regulation, body weight control, or obesity, as well as a biomarker for visceral obesity (30). In children and adolescents, leucine dietary intake was protective against obesity (31), yet in adults, the assessment of leucine intake distinctly showed a positive OR for general obesity, but not for central obesity, which was different from our research (32). On the other hand, in a case-control study, individuals with metabolic syndrome, diabetes, and obesity had lower circulating serine and proline profiles compared to healthy people with normal weight (33).
Consistent with our findings, a cross-sectional study done by Teymoori et al. reported a protective impact of tryptophan and phenylalanine as two AAAs on WC and excess body weight (17). Wang et al. found that eating tryptophan-containing foods had a significant association with the reduction in the risk of obesity and type 2 diabetes (34). When tryptophan intake was moderately limited, it increased thermogenesis and food intake; whereas in highly restriction of this AAA, energy expenditure, food intake, body weight, fat mass, and lean mass would decrease (35). Unlike our study, in the study published in 2022 dominant profile of the plasma circulating levels of AAs with a significant positive relationship with abdominal obesity, consisted of isoleucine, leucine, valine, tyrosine, tryptophan, alanine, glutamic acid, aspartic acid, histidine, methionine, asparagine, and proline. This pattern was extracted using the PCA method (20). Conflicting results observed between literature and ours may primarily result from the application of different methodologies (using plasma levels of AAs), dietary habits of participants, statistical techniques, and study design (different study participants).
In the mixed AA pattern, we found no relationship with either central or general obesity after adjustment. A study documented an inverse relationship between the high intake of 13 energy-adjusted amino acids and the risk of obesity in the Chinese population. However, this relationship was not observed for glycine, arginine, and methionine, which is consistent with our findings (36). According to Li et al., there was no correlation between methionine intake, as a SCAA, and WC. Additionally, no differences in methionine levels were observed between overweight and obese participants compared to those with normal weight, although these associations were found significant for another sulfuric AA, cysteine (15). Five essential AAs of mixed pattern were not related to obesity, however, in an experimental study, diet enriched in essential AAs reversed obesity and glucose dysregulations (37).
Regarding BCAAs which two of them dominated in the mixed pattern, a cross-sectional study on US population found no relationship between BCAAs intake and obesity, although in different populations from East Asian countries, Brazil, and UK the relationship was inversely related (38, 39). A study done in Iranian population reported no association between all BCAAs dietary intake with either abdominal obesity, or general obesity in women, which was consistent with our findings (32). On the other hand, several studies including a meta-analysis have found a protective association for BCAAs dietary intake on obesity (40-42). In an experimental study, restriction of BCAAs in a high fat diet showed protective characteristics against obesity, adipocyte hypertrophy, glucose intolerance, and inflammation (43). Ethnic disparities across Asian and non-Asian populations may influence the relationship between BCAAs intake and obesity.
In our study, there was a direct association between individuals in the first and second tertiles of the alanine AA pattern and general obesity. Sun et al. reported that there is a strong positive association between plasma levels of alanine and histidine and BMI, waist circumference, waist-to-hip ratio, and visceral fat area (20). In Japanese adults, a positive correlation was found between WC and plasma levels of alanine after adjusting for age and gender which was different from our results (21). In line with our findings, the results of a systematic review showed that histidine-containing dipeptides can decrease WC and fat mass compared to the control group (44). In addition, Okekunle et al. reported an inverse association between dietary consumption of various non-essential AAs such as histidine and the risk of obesity (36). Human clinical studies, experiments on animals, and epidemiological studies have all shown that histidine supplementation can decrease inflammation, fat mass, WC, and BMI (45-47). Histidine can reduce inflammation and oxidative stress by restricting TNF and IL-6 mRNA expression in fat cells through NF-κB and PPARγ-involved pathways (47, 48). It is noteworthy that the effects shown in the above-mentioned research are attributable to specific AAs and not to a dominant intake pattern. It is a controversial issue in the literature if dietary AA consumption influences circulatory AA levels. Moreover, it should be determined whether excessive dietary AA intake is responsible for elevated circulating AA profiles and how both are related to obesity risk (40). In sum, the results of the cited studies are contradictory, and none of them has examined all of 18 AAs that we had.
Complex interaction of physiological and environmental factors including dietary intakes affect body weight regulation. Protein or AAs as a major macronutrient of a diet can induce weight-related properties by their multiple effects on appetite, energy balance, gut microbiota, and insulin resistance (49-52). However, the relationship between AAs and obesity is highly intricate, and addressing that can have a substantial impact on weight management strategies.
The invaluable strength of this study lies in assessing the dietary intake of 18 AAs within dominant patterns in a large population. To our knowledge, this is the first study that investigated the relationship between 18 AAs intake patterns and obesity. Our study had some limitations. First, given the specific ethnicity of participants, the results of our study could not be extrapolated to the other populations. Second, the WC cutoff used for identification of central obesity was the one that was specialized for Western populations. In some literature, using WC cutoff for Iranian population is suggested. Third, due to the nature of the cross-sectional design of the study, deriving causality conclusion from our findings are implausible and needs further clinical investigations to reveal the impact of AAs in the pathogenesis or prevention of obesity.