Salt and Weight Loss: Exploring the Conflicting Research

Introduction

Salt, primarily composed of sodium chloride (NaCl), plays a vital role in maintaining bodily functions such as regulating membrane potential, fluid volume, acid-base balance, and nervous system activity. While essential for health, excessive salt consumption, particularly in the form of purified salt found in processed foods, has been linked to various health issues, including high blood pressure and potentially obesity. However, recent research presents conflicting findings, with some studies suggesting that higher sodium intake may not stimulate thirst and fluid intake, but may promote weight loss by altering the body's energy needs. This article explores the complex relationship between salt intake and weight loss, examining the evidence from various studies and considering the different types of salt and their potential effects on metabolism.

Sodium Intake and Blood Pressure: The DASH-Sodium Trial

High blood pressure (BP) affects millions of adults in the United States, increasing their risk of heart attack and stroke. Because salt consumption is thought to contribute to high blood pressure by stimulating thirst and leading to greater fluid intake, reducing salt intake is widely considered an important strategy for lowering blood pressure.

The Dietary Approaches to Stop Hypertension (DASH)-Sodium trial, a randomized controlled-feeding study published in 2001, examined the effects of three different levels of sodium intake (low, medium, and high) on blood pressure in participants following two distinct diets: a typical American diet (control diet) or a healthy diet (the DASH Diet). The researchers found that reduced sodium intake decreased participants' thirst and urine volume (a marker of fluid intake), while effectively reducing blood pressure. However, the study also noted that reduced sodium intake did not affect the amount of energy required to maintain a stable weight.

The results of the DASH-Sodium trial support the traditional view that decreasing sodium intake is critical to managing hypertension.

Sources of Sodium Intake in the Modern Diet

A contemporary study aimed to provide data on the major sources of sodium intake in a larger, more diverse sample of adults, with a particular focus on the amount and sources of sodium in the diet (e.g. added at the table and in cooking vs. sodium inherent in food). The research involved multiple sites across the US, recruiting 450 adults from diverse race/ethnic groups, with equal numbers of women and men in each group.

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The study revealed that most of the sodium comes from sodium added to food outside the home, accounting for about 70% of total sodium intake. The next biggest source was sodium inherent to food, followed by salt added in home food preparation, and salt added to food at the table. These findings highlight the significant contribution of processed and restaurant foods to overall sodium consumption, underscoring the need for increased awareness and efforts to reduce sodium content in these sources.

The Role of Salt Type: Purified Salt vs. Sea Salt

Globally, many countries predominantly eat purified (iodized), rock, and sea salt. Purified salt (99% sodium chloride, NaCl; generally called table salt) is made from sodium ion (Na+) and chloride ion (Cl−) from sea water using an ion exchange membrane electrodialysis process, and is composed of more than 99% NaCl1. Sea salt (SS) is crystallized from seawater in salt ponds using sunlight and wind2. Unlike purified salt, SS generally contains 92.4~94.4% NaCl and various other minerals, such as potassium (K), magnesium (Mg), calcium (Ca), and sulfur (S)3. This imparts numerous health functionalities to SS4,5,6,7,8,9 and a unique taste10 as compared to purified salt.

High salt consumption has synergistic effects in western diet-induced metabolic diseases11. In Europe and Northern America, most people eat processed foods (added high salt content using purified salt) compared to home cooked foods (as high as 75% in USA and UK)12. Moreover, high-income English-speaking countries have the highest rate of obesity in the world13. In addition, beverage consumption has increased the obesity risk14,15 because of their salt (purified salt) and sucrose content. Overall, one possible reason for obesity is the high intake level of purified salt16, which is cheaper than naturally manufactured salt. Therefore, most manufactured beverages and foods include purified salt, and most people unwittingly add purified salt to their diet. Dietary foods (purified salt consumption) are associated with the incidence of obesity, and purified salt intake has also been reported to increase the incidence of obesity compared to naturally manufactured salt7. It has previously been reported that SS can help to prevent obesity in high fat diet-induced obese mice, indicating that the consumption of SS may help reduce the incidence of obesity7.

Other studies have also reported that SS can help to prevent cancer4,5,6, obesity7, diabetes8, and hypertension9, as compared to purified salt (NaCl). Generally, the minerals (except NaCl) in SS include various cations, such as Mg, Ca, K, zinc (Zn), and iron (Fe)3. Few studies have reported the relationship between minerals present in the salt composition and obesity. In our previous studies of interaction between SS intake and obesity7,17, the Na:K ratio and Mg content in SS correlate with obesity in mice7 and 3T3-L1 adipocytes17. These results suggest that the beneficial health effects of SS are due to the presence of various minerals.

Mg is an essential cation essential for human homeostasis and supporting the physiological functions in the heart, brain, and skeletal muscles. The daily intake of Mg, as suggested by the United States Food and Nutrition Board is 420 mg and 320 mg for men and women, respectively18. On the other hand, current reports estimate that only 40% of Americans consume the required daily amount19. Several studies have indicated an association between the body mass index (BMI) and Mg intake status in humans20,21,22,23, but because these results are controversial24, the relationship between obesity and Mg remains unclear25.

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Depending on their manufacturing process, salt crystals differ in shape. NaCl is produced using an ion exchange membrane and subsequently blended to a powder, whereas SS is crystallized by the direct evaporation of sea water, using sunlight and wind. The method of sea water crystallization is an important step26. Typically, manufactured SS is a mixture of old- and new seawater during evaporation (generally manufactured sea salt, GS), whereas another process using only new sea water during evaporation produces cube natural sea salt (CNS). This results in differing sizes, shapes, textures, and mineral contents of Mg and S.

Cube Natural Sea Salt (CNS) and Obesity: Animal and Cell Studies

CNS Reduces Obesity in Mice with Colorectal Cancer and High-Fat Diet

The study investigated the effects of CNS on mice with azoxymethane/dextran sodium sulfate + high fat diet induced colorectal cancer and obesity on C57BL/6 mice. The results showed that at seven weeks, the weight of the mice was observed to be the highest in the high fat diet group (32.2 ± 3.7 g), whereas the Normal (27.1 ± 1.2 g), A/D + HFD (azoxymethane (A)/dextran (D) + high fat diet (HFD)) (26.4 ± 0.9 g), A/D + HFD + GS (26.3 ± 1.7 g), and A/D + HFD + FS (FS, filtering sea water after evaporating sea salt) (26.2 ± 1.1 g) groups showed similar weights. The A/D + HFD + CNS group (24.3 ± 1.0 g) showed significantly lower body weight than the A/D + HFD group. At eight weeks (after fasting, except HFD), all mice body weights were similar, except for the HFD group. The normal group had a significantly different average food intake (AFI) compared to the other groups (Supplement Fig. 1A). The A/D + HFD-treated groups had a significantly different AFI compared to the HFD group at two and four weeks during the DSS treatment period, whereas at three and five-six weeks, the A/D + HFD groups were similar to the others. The normal group had a significantly increased food conversion ratio (FCR) compared to the HFD group at six and seven weeks (Supplement Fig. 1B). At two and four weeks, the standard deviations of the FCRs of the A/D + HFD as well as A/D + HFD + GS, FS, and CNS groups were large, and the FCR increased because the body weight gain value was negative upon the administration of D. At three and five-seven weeks, however, the group treated with A/D did not show a significant difference overall. The liver, testis, and kidney weights were similar among the groups (data not shown). Therefore, the A/D + HFD + CNS group had the lowest body weight at seven weeks, and 1% sea salt intake had no effect on AFI or FCR in mice.

The consumption of a HFD is associated with an increased size and number of adipocytes27. The epididymal fat size of all mice fed HFD was larger than that of normal mice. The CNS-treated mice showed a significantly reduced fat size and inflammation compared to the A/D + HFD group as well as a significantly reduced epididymal fat weight compared the A/D + HFD group (P < 0.05). Therefore, the CNS treatment reduced the fat size and weight in the fat and liver tissues as well as the body weight of A/D + HFD-induced mice.

CNS Regulates Obesity-Related Genes in Mice

The sterol regulatory element-binding protein 1 (SREBP-1) and fatty acid synthase (FAS) expression levels were elevated in the HFD group and significantly lower in all groups treated with A/D compared to the HFD group. On the other hand, in the case of peroxisome proliferator-activated receptor gamma (PPARγ), the A/D + HFD and A/D + HFD + GS groups were similar to the HFD group, whereas the A/D + HFD + FS and A/D+HFD + CNS groups showed lower PPARγ expression than the HFD group. In particular, the A/D + HFD + CNS group showed the lowest level of PPARγ mRNA expression, similar to that of the Normal group. The A/D-treated groups also showed lower diglyceride acyltransferase 2 (DGAT2) mRNA expression than the HFD group, and the A/D + HFD + CNS group showed the lowest DGAT2 expression (P < 0.05). The lipoprotein lipase (LPL) and DGAT2 levels were up-regulated in the HFD group compared to the Normal group. The A/D + HFD and A/D + HFD + GS groups showed the highest LPL and DGAT2 protein expression levels. On the other hand, the A/D + HFD + CNS group showed significantly lower LPL and DGAT2 levels in the liver and epididymal fat tissues compared to the A/D + HFD and A/D + HFD + GS groups (P < 0.05), whereas DGAT2 expression was similar to the Normal group.

Overall, CNS intake reduces obesity compared to other types of sea salt in A/D + HFD induced mice. On the other hand, the A/D + HFD model is a dual disease-induced mouse model. In this model, the mouse body weight loss and reduction of obesity-related gene expression cannot be attributed directly to the sea salt or A/D treatment. Therefore, this study investigated the relationship between sea salt and obesity in 3T3-L1 adipocytes and HFD-induced obese mice.

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CNS Treatment Reduces Obesity in 3T3-L1 Adipocytes

The survival rate of the 1% sea salt groups was not reduced significantly (Supplement Fig. 2A). NaCl was not used in the experiment because of the significantly different cytotoxicity between NaCl and CNS (Supplement Fig. 2B). In addition, 1% CNS reduced the cell viability of differentiated 3T3-L1 adipocytes compared to other salts (Supplement Fig. 2C).

CNS resulted in a significant reduction of Oil red O-stained fat compared to the Control, GS, and FS. CNS resulted in significantly decreased mRNA expression levels of PPARγ (0.39 ± 0.3), SREBP-1 (0.42 ± 0.21), CCAAT-enhancer-binding proteins alpha (C/EBPα) (0.14 ± 0.04), liver X receptor alpha (LXRα) (0.22 ± 0.17), FAS (0.44 ± 0.15), DGAT2 (0.53 ± 0.21), and LPL (0.42 ± 0.32) in differentiated 3T3-L1 adipocytes compared to the Control (P < 0.05). In addition, CNS resulted in significantly reduced levels of SREBP-1 protein expression (0.42 ± 0.02) compared to the Control (fold ratio: 1) (P < 0.05). Therefore, CNS inhibits adipo/lipogenesis via the regulation of related gene expression.

CNS Intake Reduces Obesity Parameters in Mice Fed a High-Fat Diet

A high fat diet (HFD) group of animals gains more weight than those fed a normal diet. Because this study focused on the interaction between HFD and salt samples, only the HFD and HFD + sample treated groups were compared; a normal diet group was not included. A significant decrease in body weight was observed in the CNS treatment group as compared to the NaCl (Reagent, Sigma-Aldrich Co., St. Louis, MO, USA) group at 12-16 weeks (P < 0.05). At 17 weeks, the reduction in body weight was significantly different in the CNS group (36.2 ± 4.9 g) than both the NaCl group (42.5 ± 3.5 g) and GS group (41.5 ± 5.0 g) (P < 0.05). No significant difference in the AFI was observed between the groups (Supplement Fig. 3A). On the other hand, the CNS group had a significantly higher FCR than the HFD group at 16 and 17 weeks (Supplement Fig. 3B). At nine weeks, all mice inadvertently showed a decrease in body weight with a reduced AFI and enhanced FCR. After nine weeks, however, the body weight, AFI, and FCR of all the mice returned to normal conditions.

The measured serum lipids profiles revealed a significant reduction of triglyceride (TG), total cholesterol (TC), and low density lipoprotein (LDL) in the CNS group as compared to the NaCl group (P < 0.05). In addition, the CNS group showed significantly reduced leptin levels (a serum obesity related hormone) as compared to HFD, NaCl, and GS groups (P < 0.05). The liver enzyme concentrations showed significant reduction of aspartate transaminase (AST) and alanine transaminase (ALT) in the CNS group as compared to the NaCl group (P < 0.05). On the other hand, the Na concentrations and glucose level in the serum remained unaffected with all salt treatments (Supplement Fig. 4A,B), indicating that the type of salt has no effect on the glucose metabolism, and 1% salt intake does not influence blood homeostasis in mice.

These observations showed that the CNS group had the lowest body weight at 17 weeks. Although the AFI or FCR were unaffected by 1% NaCl and the sea salt intake, the CNS group showed enhanced FCR at 16 and 17 weeks. In addition, the serum examination revealed reduced lipid accumulation, leptin and liver enzymes in the CNS group. Overall, NaCl intake increases obesity, but the CNS intake results in decreased obesity compared to NaCl intake in HFD-induced obese mice.

Salt Intake and Diet-Induced Thermogenesis (DIT)

High salt intake ranks among the most important risk factors for noncommunicable diseases. Western diets, which are typically high in salt, are associated with a high prevalence of obesity. High salt is thought to be a potential risk factor for obesity independent of energy intake, although the underlying mechanisms are insufficiently understood. A high salt diet could influence energy expenditure (EE), specifically diet-induced thermogenesis (DIT), which accounts for about 10% of total EE.

A randomized, double-blind, placebo-controlled, parallel-group study investigated the influence of high salt on DIT. Forty healthy subjects received either 6 g/d salt (NaCl) or placebo in capsules over 2 weeks. Before and after the intervention, resting EE, DIT, body composition, food intake, 24 h urine analysis, and blood pressure were obtained. EE was measured by indirect calorimetry after a 12 h overnight fast and a standardized 440 kcal meal.

The change in DIT differed significantly between groups (placebo vs. salt, p = 0.023). DIT decreased by 1.3% in the salt group (p = 0.048), but increased by 0.6% in the placebo group (NS). Substrate oxidation indicated by respiratory exchange ratio, body composition, resting blood pressure, fluid intake, hydration, and urine volume did not change significantly in either group. A moderate short-term increase in salt intake decreased DIT after a standardized meal.

Novel Approaches: Liquid Salts and Fat Absorption

A new study from Harvard's Wyss Institute for Biologically Inspired Engineering and John A. Paulson School of Engineering and Applied Sciences (SEAS) explored a novel approach to reducing fat absorption using a liquid salt. The orally administered liquid salt, called choline and geranate, or CAGE, can physically limit the absorption of fats from food with no discernable side effects in rats, and reduce total body weight by about 12 percent.

The researchers found that CAGE caused rats to gain 12 percent less weight than rats that received either a lower dose or no CAGE. Importantly, over the 30-day time period, no side effects were observed in the rats treated with CAGE, and there were no signs of inflammation or differences in the animals' organ structure or function.

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