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Despite recent evidence pointing to sugar intake as a driver of hypertension,¹ it is still salt that is king, at least in terms of the evidence implicating it in hypertension risk. Taste preference for salt varies across the population, as does the impact that salt has on blood pressure and other cardiometabolic conditions. Two new studies highlight how both behavioral preferences and genetic differences affect cardiometabolic health in important ways and how these individual differences can play a major role in the ultimate impact.

First, a brief overview of the two studies, which are quite different in several ways. One is an interventional trial of the effect of dietary sodium on blood pressure within a sample from a primarily Black and female population.² The other examines preference for salt intake and incident type 2 diabetes (T2D) among over 400,000 primarily white participants in the UK Biobank.³ Both studies relate sodium intake to increased cardiometabolic risk; however, it is the individual differences among participants and their potential impact on personalizing treatment plans that are among the most relevant takeaways for practicing functional medicine clinicians.

Low-Sodium Diet and Blood Pressure Reduction

The first study mainly used participants from CARDIA (Coronary Artery Risk Development in Young Adults), a prospective observational cohort study that has been following individuals enrolled since 1985-1986 in four US cities (Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA). A total of 213 individuals (65% female, 64% Black) now aged 50 to 75 years attended a baseline visit while consuming their usual diet and then completed one-week high and low-sodium diets. Participants included people with normotension (25%), controlled hypertension (20%), uncontrolled hypertension (31%), and untreated hypertension (25%).²

In a crossover design, participants were assigned to either one week of a high or low-sodium diet and then switched to the other type of diet for the second week. These diets were achieved in very different ways: for the high-sodium diet, researchers simply provided participants with two bouillon packets (2,200 mg sodium) to add to their existing diet, while the low-sodium diet consisted of meals, snacks, and beverages prepared in metabolic kitchens along with instructions not to consume anything else. The low-sodium diet contained about 500 mg of sodium and 4,500 mg of potassium daily.²

The difference in systolic BP following one week on a high-sodium versus a low-sodium diet was 8 mm Hg as measured by 24-hour ambulatory monitoring (P<0.001). Mean differences in diastolic BP, mean arterial pressure (MAP), and pulse pressure (PP) between individuals randomized to a high vs low-sodium diet were also significant. What got the most attention in the media, though, was that the decline in BP going from a high to a low-sodium diet was the same (not significantly different), regardless of hypertension status and antihypertensive medications used.² This is interesting to note and provides an excellent demonstration of the fact that dietary interventions can have effects beyond those of pharmaceuticals even when taken together, but another important finding got less attention.

While some headlines said something along the lines of “everyone can benefit from lowering their salt intake,” the results actually do not bear that out. One of the primary goals of the study was to look at salt sensitivity of blood pressure (SSBP), the within-individual BP response to variation in sodium intake. Using the usual cutoff of 5 mm Hg, the study found that only 46% of those in the study showed such a decline, which generally accords with previous estimates that about half of people with hypertension, and a quarter of those without, are salt sensitive⁴ (about 75% of those in the study were hypertensive). The study, however, did not find a difference in SSBP between those with hypertension and those without, although the authors note that sample size may have made the study underpowered to find such an effect.

Perhaps more interesting was the huge variation in response to the low-sodium diet across participants. While MAP declined in about 73% of people following the low-sodium diet, it actually increased in more than 25% of individuals, and 5% of those actually showed inverse SSBP (an increase of 7 mm Hg or more on the low-sodium diet).² Moreover, the figure showing individual responses makes it clear that the average decline was driven by a small number of people who showed huge changes, followed by about a quarter of people who had clearly significant reductions. Many of the rest had no reduction (or indeed, an increase) or small reductions that may or may not be clinically significant.

While it is important to note that a one-week intervention might not be expected to have the same effect as longer-term dietary change, there is considerable variability among individuals. Due to genetics, metabolism, and other factors, people’s response to sodium intake changes is different, which should be taken into account when dietary interventions are designed for hypertension. For many individuals, reducing sodium intake may not have a meaningful impact on BP and thus we may want to prioritize other types of dietary interventions (listed below).

Finally, it is also important to note that consuming a high-sodium diet did not change BP when compared to baseline diets, showing a ceiling effect of sorts: this population already collectively consumed a high amount of salt (in this study, 24-hour urine sodium excretion estimated the median daily sodium intake at baseline as ~4.5 g), so 2 g more salt daily didn’t seem to do much to BP in this time frame. Also, while baseline potassium intake wasn’t reported, the 9:1 K+/Na+ ratio used in the low-sodium intervention is worlds apart far from the normal intake ratio of a Western diet.

Dietary Salt Preference and Type 2 Diabetes

Meanwhile, across the Atlantic, researchers examined the connection between personal use of salt as a seasoning on meals (post-cooking) and incident T2D in a prospective cohort study. They identified 402,982 participants (54% female, 95% white) in the UK Biobank who were healthy at baseline and had completed a questionnaire about the frequency with which they added salt to food (never, rarely, sometimes, usually, or always). After following participants for a mean of about 12 years until either diagnosis of diabetes, death, or the end of the study, they found that compared to those who “never” or “rarely” added salt to food, the sex- and age-adjusted hazard ratios (HRs) for developing T2D were 1.20, 1.32, and 1.86 for those who reported “sometimes,” “usually,” and “always” adding salt, respectively (P< .001). After adjusting for several lifestyle, socioeconomic, and other traditional risk factors for T2D, the results attenuated a bit but were all still significant. After collecting urine specimens that measured sodium intake, the researchers found a dose-dependent relationship across quintiles of urinary sodium and higher T2D risk, with HRs of 1 (reference), 1.12, 1.17, 1.28, and 1.34, respectively. Note that all groups had sodium excretion of over 3 g per day.³

The researchers noted that body fat percentage and body fat mass significantly mediated the association of adding salt with T2D, explaining an estimated (overlapping) 37.9% and 39.9% of the effect, respectively (both P < .001). Hs-CRP levels also accounted for about 9% of the variance. The researchers could not completely exclude the possibility that high frequency of adding salt to foods is a marker for an unhealthy lifestyle.³ The study did not examine the relationship between SSBP and those who developed diabetes, though it might be tempting to speculate that those who are sensitive to sodium would be more likely to develop health repercussions, including T2D.

Personalizing Diets

From an intervention perspective, it is interesting that little is known about the reasons driving individual differences among people in their propensity to add salt to their food. Perhaps it has much to do with tastes developed during childhood, or with some interaction of genetic and environmental factors. Clearly, sodium is a required nutrient that humans evolved to find rewarding thanks to the dopamine system. Why some people crave it more than others is still a matter of debate. Regardless, helping some patients decrease their salt usage should include some measure of meeting them where they are. Finding suitable substitutes and understanding that not everyone will be able to sustain a diet that has a 9:1 K+ to Na+ ratio is an important consideration.

As always in functional medicine, appreciating the individual differences among patients and adjusting dietary plans accordingly is crucial. Whether it is a dietary preference or a physiological response, every patient is different, and the only way to find a dietary plan that is both effective and sustainable is to listen to the patient and use all the information available to you to help tailor a plan that works. Keeping in mind that sodium may not be a major factor for many patients with hypertension suggests that considering prioritizing other dietary adjustment may provide more benefit, especially for those in which sodium reduction has been tried but is less effective. These may include limiting other known BP-increasing dietary factors such as added sugars¹ and saturated fatty acids^5,6 and increasing intake of elements associated with decreasing BP, such as unsaturated fats,⁷ protein,⁸ potassium,⁹ fiber,^10,11 and potentially magnesium.¹²

References

1. Mansoori S, Kushner N, Suminski RR, Farquhar WB, Chai SC. Added sugar intake is associated with blood pressure in older females. Nutrients. 2019;11(9):2060. doi:3390/nu11092060
2. Gupta DK, Lewis CE, Varady KA, et al. Effect of dietary sodium on blood pressure: a crossover trial. JAMA. Published online November 11, 2023. doi:1001/jama.2023.23651
3. Wang X, Ma H, Kou M, et al. Dietary sodium intake and risk of incident type 2 diabetes. Mayo Clin Proc. Published online October 11, 2023. doi:1016/j.mayocp.2023.02.029
4. Weinberger MH, Miller JZ, Luft FC, Grim CE, Fineberg NS. Definitions and characteristics of sodium sensitivity and blood pressure resistance.Hypertension. 1986;8(6 pt 2):II127-II134. doi:1161/01.HYP.8.6_Pt_2.II127
5. Nakamura H, Tsujiguchi H, Kambayashi Y, et al. Relationship between saturated fatty acid intake and hypertension and oxidative stress. Nutrition. 2019;61:8-15. doi:1016/j.nut.2018.10.020
6. Gou R, Gou Y, Qin J, et al. Association of dietary intake of saturated fatty acids with hypertension: 1999-2018 National Health and Nutrition Examination Survey. Front Nutr. 2022;9:1006247. doi:3389/fnut.2022.1006247
7. Schwingshackl L, Strasser B, Hoffmann G. Effects of monounsaturated fatty acids on cardiovascular risk factors: a systematic review and meta-analysis. Ann Nutr Metab. 2011;59(2-4):176-186. doi:1159/000334071
8. Rebholz CM, Friedman EE, Powers LJ, Arroyave WD, He J, Kelly TN. Dietary protein intake and blood pressure: a meta-analysis of randomized controlled trials. Am J Epidemiol. 2012;176 (Suppl 7):S27-S43. doi:1093/aje/kws245
9. Filippini T, Naska A, Kasdagli MI, et al. Potassium intake and blood pressure: a dose-response meta-analysis of randomized controlled trials. J Am Heart Assoc. 2020;9(12):e015719. doi:1161/JAHA.119.015719
10.  Whelton SP, Hyre AD, Pedersen B, Yi Y, Whelton PK, He J. Effect of dietary fiber intake on blood pressure: a meta-analysis of randomized, controlled clinical trials. J Hypertens. 2005;23(3):475-481. doi:1097/01.hjh.0000160199.51158.cf
11.  Reynolds AN, Akerman A, Kumar S, Diep Pham HT, Coffey S, Mann J. Dietary fibre in hypertension and cardiovascular disease management: systematic review and meta-analyses. BMC Med. 2022;20(1):139. doi:1186/s12916-022-02328-x
12.  Asbaghi O, Hosseini R, Boozari B, Ghaedi E, Kashkooli S, Moradi S. The effects of magnesium supplementation on blood pressure and obesity measure among type 2 diabetes patient: a systematic review and meta-analysis of randomized controlled trials. Biol Trace Elem Res. 2021;199(2):413-424. doi:1007/s12011-020-02157-0