This cross-sectional study is, to the best of our knowledge, the first to examine the association in human population samples between MSG intake and overweight. A positive relation prevailed with control for physical activity, total energy intake, and other possible confounders. Although animal studies have indicated for decades that MSG intake may cause overweight or obesity, data on the human species have been lacking, possibly because MSG is widely used in commercially processed foods, hence it is difficult to measure intake, particularly in developed countries. INTERMAP Chinese participants were from rural areas in China. In 1997 when the population-based INTERMAP field surveys were done, most foods eaten by Chinese participants were prepared in their households (by themselves or by their spouses). Thus, they lent themselves particularly to the investigation of MSG intake in relation to overweight/obesity.
These positive associations between MSG intake and overweight are generally consistent with data from animal studies. In 1969, it was first reported that weight gain in 4 months was significantly greater in both male and female mice with large-dose MSG-administration immediately post-birth compared to controls, even though the controls had slightly larger food consumption.5
Hypothalamic lesions were found in the MSG-treated animals. The investigator suggested that a regulatory mechanism affecting fat metabolism in the mouse, other than appetite disturbance, should be considered as linking MSG intake with obesity. Recently, the MSG-obesity hypothesis has been re-formulated, i.e., chronic MSG intake may intoxicate arcuate nucleus neurons and disrupt the hypothalamic signaling cascade of leptin action, causing leptin resistance related to overweight/obesity.9, 10
MSG ingestion as a cause of hypothalamic damage has been debated for decades. Some animal studies suggest that injection of MSG may induce neuronal necrosis in several brain regions including the hypothalamus.5, 20–25
Since destruction of hypothalamic neurons in animals results in a complex neuroendocrine deficiency syndrome, concern has arisen that ingestion of MSG by humans may contribute to occurrence of neuroendocrinopathies.26, 27
Most of the evidence on hypothalamic lesions and appetite regulation was provided from laboratory animals that were injected with MSG at neonatal age. While the deleterious effects of MSG injection on hypothalamic neuronal circuitries have been well documented, limited studies have been published on the effects of orally administered MSG.12, 28
Some researchers are unconvinced that oral MSG affects appetite regulation.29
Further studies are clearly needed. Nevertheless, the findings from our study support the judgment against MSG supplementation of human nutrition.
In addition, studies have indicated an important role for leptin in regulating food intake and energy balance.30, 31
Leptin receptor mRNA is present in the hypothalamus, postulated as a potential site of action for leptin.32
Leptin production is increased in animal models of obesity associated with experimentally induced hypothalamic damage, including the MSG-treated model.33
One study found that leptin suppressed body weight gain in controls but did not suppress weight gain in MSG-treated rats.6
This finding suggests that destruction of neurons in the hypothalamus by MSG can attenuate the actions of leptin. Another study reported that leptin significantly inhibited food intake and caused weight loss in control rats whereas MSG-treated rats were unresponsive to leptin treatment.7
The authors suggested that the hypothalamic arcuate nucleus is essential for mediating the anorectic effects of leptin influencing energy balance. Human hypothalamic obesity has been reported in humans due to hypothalamic damage from tumour, 34, 35
as well as in animals after neonatal administration of MSG.5, 36
A recent study reported that MSG maintains its toxicity in animals when administered orally, and that MSG at concentrations only slightly surpassing those found in everyday human food has potential for damaging hypothalamic regulation of appetite.12
An alternative mechanism for the possible linkage of MSG to obesity is that MSG may regulate adipsin and thereby change body composition. Adipsin is synthesized and secreted by adipocytes. Depressed adipsin expression has been associated with obesity in animal models.37
Mice treated with MSG had 50% lower serum adipsin and over 2-fold higher percentage of body fat than lean controls.38
A positive association between MSG intake and overweight may be a result of greater voracity since MSG or leptin resistance can stimulate appetite. In the INTERMAP Chinese samples, participants with higher MSG intake tended to have higher total energy intake. However, our findings are independent of total energy intake. Presumably, the weight gain independent of total energy intake and physical activity was due to decreased non-exercise energy expenditure, e.g., thermogenesis.39, 40
Our findings are unlikely to be due to chance. The multivariable adjusted positive associations are statistically significant, and prevailed for men and women. Also, the associations were present using either the international standardized cut-off (BMI ≥25.0) or the WHO recommendation (BMI ≥23.0) for overweight for Asian populations.
One concern is the accuracy of the MSG measurement. Similar to other food additives such as table salt (NaCl), MSG intake is difficult to quantify accurately with existing dietary assessment instruments. However, our estimation of MSG intake in INTERMAP is unlikely to be substantially biased. First, all foods eaten by the great majority of INTERMAP Chinese participants were exclusively prepared in their households. Second, the amounts of MSG added to foods during preparation appear to be habitual and were demonstrable by participants in the diet assessment. Third, although estimates of absolute intake of MSG may have been limited in precision, we apparently were able to identify MSG users and non-users. In fact, the prevalence of overweight for MSG users was significantly higher compared to MSG non-users, in addition to the positive trend for relation of amount of MSG intake to BMI. Finally, measurement error is likely to be non-differential, tending to dilute any observed association.
Another relevant question is: why are Asian populations relatively lean since MSG use is popular in Asian cuisine? A possible explanation is that an adverse effect of MSG intake on body weight may be attenuated by lower caloric density of foods and other lifestyle factors such as greater physical activity in Asian populations compared to Western. For example, the average amount of heavy activity per day for INTERMAP rural Chinese participants was 2.4 hours (standard deviation=3.7) for men and 1.7 hours (3.2) for women, indicating relatively higher energy expenditure in this group.
In this study, our ability to examine the relation of MSG intake and obesity was limited by small number of persons (3%) with BMI ≥30.0. However, the partial correlation between MSG intake and BMI approached significance. Hence it is reasonable to infer that MSG intake is also associated with higher prevalence of obesity. This study is also limited by lack of data on leptin and adipsin concentrations. In addition, the INTERMAP findings are cross-sectional, but nevertheless unique; this topic has not been previously pursued in human population samples.
In conclusion, we found a positive relation of MSG intake to BMI that persisted with controlling for physical activity and total energy intake among apparently healthy Chinese adults. MSG intake was significantly related to prevalence of overweight. This study is of public health interest because MSG is increasingly used worldwide. This study also provides the first human data on this issue and raises a concern about MSG use and body weight in addition to allergenic effects. Further studies are needed to determine reproducibility of these findings, elucidate their etiopathogenetic pathway, and amass the evidence needed to assess whether the relation between MSG intake and body weight is causal.