The rate of heat-related morbidity and mortality increases with the process of climate change, especially for workers and athletes (1–3). Exposure to a hot and humid environment increases metabolic rates and heat production. Meanwhile, body heat dissipation also increases, with increase in sweating and cutaneous vasodilation. Consequently, the cardiovascular system responds by increasing heart rate and cardiac contractility and reducing blood flow from non-cutaneous regions (4). A huge body of studies has concluded that high environmental temperature negatively affects the physical performance and exacerbates poor cognitive function (5–8). Beyond that, a hot environment augments immune disturbance (9–11) and oxidative stress (production of reactive oxygen species (ROS) and lipid peroxidation, etc.) (12, 13). On the whole, all the physiological mechanisms believed to cause injury with hot conditions alone are markedly aggravated further with physical activities (14–17).

However, most of the studies are conducted to provide nutrient supplements under thermal conditions. In addition, there is no conclusive instruction about the kind and amount of nutrients to consume. Accumulating evidence has proven that chronic exposure to a hot environment leads to nutrient deficiency. For instance, several minerals (such as sodium, potassium, calcium, magnesium, iron, and iodine) and water-soluble vitamins (vitamin B and vitamin C) were lost while sweating (18–21). Some scientists recommended that it is not necessary to consume nutrient supplements since they could be replenished if they follow a normal diet. Notwithstanding, researchers found nutritional supplements to be an ergogenic aid and to repress oxidant and inflammatory responses. Carbohydrate supplementation had a benefit on endurance (22) and anaerobic (23) performance. Supplementation with sodium helped in preventing heat cramping (24). Vitamin C supplementation decreased post-exercise cortisol in athletes anticipating marathons in a hot environment (25).

Moreover, not all studies concluded that nutrient supplementation was effective when a single nutrient was used. Actually, it is not an independent consequence of a single mechanism but the complex interaction of the entire body that responds to the physical strain caused by the combination of a hot environment and physical activities. Given the scarcity of literature concerning this, the current study aimed to explore the effect of multiple-nutrient supplement supplementation on strenuous activity in a hot environment and its advantage, if any, over glucose and water consumption.

In this study, faster recovery from muscle damage and compromised liver and renal function were found with supplementation with multiple nutrients after exercising in hot conditions. A pilot trial and a randomised controlled trial were constructed in the present study. The change in BUN at POST and changes in AST, Cr, and UA at REC significantly decreased after a single-shot supplement in the pilot trial. Data obtained in the short-term supplement trial corroborate the findings in the pilot trial. Multiple-nutrient supplementation significantly decreased changes in AST, CK, and LDH in the REC after a 7-day supplement. Meanwhile, a tendency to suppress the elevation of Cr and UA was found.

Either intense physical activity or heat exposure depresses glomerular filtration and renal plasma flow, thus leading to retention of UA and Cr (33). Cr was produced from the breakdown of creatine phosphokinase in muscle. Nucleic acids released from damaged muscle increased UA generation. However, multiple-nutrient supplementation attenuated kidney excretion suppression and accelerated the clearance of metabolites in this study. Additionally, dehydration can lead to the elevation of Cr and BUN. The least elevation of multiple-nutrient supplement of Cr indicates better hydration in the pilot trial. It has been proven that heat- and exercise-induced muscle damage, inflammatory responses, and oxidative stress can cause acute kidney injury (34, 35). In the current study, multiple-nutrient supplementation may attenuate these stresses to protect the kidney.

Similarly, intense exercise under heat can induce muscle damage, liver hypoperfusion, and ischaemia. Then, the repair signal was activated, and the migration of circulating blood neutrophils and monocytes toward the damaged site was triggered. Immune cells promote the degradation of cellular debris and phagocytosis by producing free radicals, which leads to secondary damage and increased permeability of the membrane. As a result, increased levels of AST, CK, and LDH are released into the bloodstream (36). Our results support previous findings that the levels of AST, CK, and LDH increased after exercise (37, 38).

In the present study, we noticed a greater AST elevation in the multiple-nutrient supplement group immediately after the running test. However, it decreased rapidly during recovery, which means that its transient elevation could be physiological. Significantly greater AST, CK, and LDH activities for glucose and water supplementation during recovery suggest greater membrane damage caused by lipolytic enzymes activated by pro-inflammatory cytokines (36, 39).

Antioxidants were generally used in sports supplements. Recently, a meta-analysis concluded that vitamin C attenuated oxidative stress and the inflammatory response (40). Beyond that, studies found that taurine ingestion for 7 days to 8 weeks decreased oxidative stress in both cyclists and triathletes (41, 42). Previous studies found that antioxidants could protect the liver from exercise-induced damage by modulating the mRNA expression of both inflammation-related and oxidative-related signal transduction pathways (43, 44). Similarly, a greater elevation of SOD after the running test and a smaller change in 8-iso-PGF2α during recovery suggest that multiple-nutrient supplementation upregulated plasma antioxidant potential and helped prevent lipid peroxidation in this study. Simultaneously, greater elevations in inflammatory factors were detected after the running test in the carbohydrate group and water group than in the multiple-nutrient supplement group in our study. Therefore, it can be postulated that anti-inflammatory and antioxidative ingredients attenuate secondary damage to healthy myocytes.

Moreover, additional vitamin K2 was added to the multiple-nutrient supplement in the short-term supplement trial. Vitamin K2 (MK-7) was formerly used to prevent bone fracture. More recently, MK-7 has been found to be a bioactive compound that promotes ATP production by increasing the efficiency of the electronic transportable chain. Moreover, vitamin K2 could prevent inflammation and ROS accumulation without the risk of negative side effects or overdosing (45, 46). However, there is still a dearth of research focusing on its effect on physical exercise under heat. In the current study, an extra effect of decreased changes in CK, LDH, IL-6, TNF-α, and 8-iso-PGF2α during recovery was found, as expected, which indicated enhanced membrane integrity and reduced leakage of enzymes caused by secondary damage.

Furthermore, we found that serum glucose increased POSTs in both the single-shot supplement trial and short-term supplement trial. Similar results can be found from the former studies that exercise after fasting overnight does not necessarily lead to a drop in glucose concentration (47). This may be due to the breakdown of muscle glycogen during intense activities.

A large number of subjects were enrolled in this study. The findings of the short-term supplement trial can further confirm those in the pilot trial. However, there are still some limitations to this study. First, this study consisted of two single-blinded trials, which could introduce potential bias. However, this allowed us to respond to emergencies and gastrointestinal symptoms, for example, in time. Moreover, we managed to control for potential bias while conducting these two trials. Participants were numbered randomly, and all data collection was performed according to their number. Only researchers who distributed beverages knew the grouping, and those who helped collect and analyse data did not. These two trials further validated each other. Although we managed to be unbiased, we still do not think that they were enough to be called as double-blinded trials. Second, men are more likely to engage in occupations that need to perform physical activity in hot environments. Current research has not focused on whether multiple-nutrient supplementation is equally effective in women. Finally, we found the effect of multiple-nutrient supplementation on attenuating the elevation of CK and LDH in the second trial but not in the pilot trial. Whether the benefit is due to the longer period supplementation or the extra addition of vitamin K2 is not explored in this study. Further studies are warranted to investigate the exact effect and mechanism behind this.

The current study found that multiple nutrient supplements promoted the recovery of muscle damage, liver function, and kidney function, probably by reducing secondary damage and accelerating the clearance of metabolic products after exercising under heat. This study will provide evidence for further nutritional recommendations that instruct workers and athletes who engage in heavy physical activities under heat to recover in a timely manner.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by the 962nd Hospital of the PLA Joint Logistic Support Force Ethics Committee and Harbin Medical University Ethics Committee. The patients/participants provided their written informed consent to participate in this study.

YL, XuW, and CW contributed to conceiving and designing this study. CW, SZ, YZ, WG, SL, and BL performed the literature review, carried out the experiment, and collected data. YZ analysed and interpreted the data. CW and SZ wrote the first manuscript. WG, SK, and XuaW revised the manuscript. The final version of this manuscript was checked and approved by all the listed co-authors. All authors contributed to the article and approved the submitted version.

This study was supported by PLA logistic research project (NO. AWS16J023).

The 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.