I’ve previously discussed how blood pressure is one of the most important modifiable risk factors to optimize cardiovascular health. We have evidence from RCTs, observational studies, and mendelian randomization studies showing the importance of controlling and optimizing blood pressure to reduce major adverse cardiac events (MACE) and all-cause mortality.
Mendelian randomization (MR) studies have found a 45% relative lifetime risk reduction in cardiovascular events for every 10 mmHg decrease in systolic blood pressure.1 Mendelian randomization studies highlight the cumulative nature of risk increase that occurs with time, speaking for the importance of early intervention, which I’ve written about here.
At the same time, prospective cohort studies indicate that coronary artery disease and stroke mortality increase by at least two folds for every 20/10 mmHg increase in blood pressure, starting at 115/75 mmHg.2
Moreover, a number of large meta-analyses looking at randomized controlled trials have consistently found the rate of stroke and coronary artery disease (CAD) to be significantly less in people who have tight blood pressure control on treatment in comparison to those who don’t. Pharmacological lowering of blood pressure with 10/5 mmHg reduces strokes by at least 30% and reduced CAD-associated MACE by about 16%.3
So there’s really no questioning the importance of having near-optimal blood pressure if one wishes to avoid MACE. With the prevalence of hypertension and elevated blood pressure being as high as it is (about 50% of over 30yo are estimated to be hypertensive, i.e. having BP > 140/90 mmHg4), it’s clear that we’re not delivering on this crucial area of health. This has naturally led me to consider the low-hanging fruit for blood pressure optimization.
Maintaining a healthy body weight, regular exercise, not smoking, not consuming too much alcohol, maintaining emotional resiliency, and reducing stress are all things that we know impact BP in a positive direction. This being said, without overlooking the importance of a multimodal approach, I’m mostly going to focus here on salt and potassium. In Vaguely on Salt, I discussed some of the physiology and controversies related to the maintenance of sodium balance and the association between sodium intake and morality. Here I’m going to dig a bit deeper into the literature on especially sodium and potassium intake.
If nothing else, the one thing that every medical student takes with them from nephrology class is that western societies consume too much salt, that we far exceed the physiological requirements for sodium, and that we all should reduce our salt intake. And really, besides the many mechanistic arguments for why sodium would increase blood pressure and contribute to kidney disease, the associations between increased blood pressure, cardiovascular disease, and elevated sodium intake are not trivial, to say the least. And as convincing is the data on sodium restriction, up to a certain point, which further strengthens the case against sodium.
The studies looking at the correlation between sodium intake and any given outcome usually estimate intake based on urinary excretion. I could potentially imagine some situations where this is problematic, but as far as I’m aware this method has been established as accurate and representative of sodium intake.
The most often cited study when it comes to sodium intake might be Urinary Sodium and Potassium Excretion and Risk of Cardiovascular Events, in which the authors famously presented the U-shape relationship between sodium intake and mortality:
Compared with baseline sodium excretion of 4 to 5.99 g per day, higher baseline sodium excretion of 7-8 g/d and lower sodium excretion of 2-2.99 g/d were associated with an increased risk of the composite of CV death, MI, stroke, and hospitalization for CHF on multivariable analysis. (edited)
People whose sodium excretion was 7-8 g/d and over 8 g/d had 15% and 49% more adverse events, respectively, and people whose sodium excretion was 2-3 g/d and less than 2 g/d had 16% and 21% more adverse events, respectively. This speaks to an optimum sodium intake being somewhere around 5 grams of sodium per day, corresponding to about 12 grams of salt per day.
The same study also found an inverse association between stroke and potassium excretion:
Compared with an excretion of less than 1.5 g per day, higher potassium excretion was associated with a reduced risk of stroke (HR 0.77 for 1.5-1.99 g/d; HR 0.73 for 2-2.49 g/d; HR 0.71 for 2.5-3 g/d; and HR 0.68 for >3 g/d) on multivariable analysis. (edited)
29.8%, 37%, 41%, and 47% reduced risk for 1.5-1.99 g/d, 2-2.49 g/d, 2.5-3 g/d, and >3 g/d, respectively. This quite strongly speaks for a higher potassium intake when considering stroke risk, but the study didn’t establish any meaningful association between other adverse events and potassium intake.
Another quite often cited study, namely Intersalt: an international study of electrolyte excretion and blood pressure, and a secondary analysis named Intersalt revisited: further analyses of 24-hour sodium excretion and blood pressure within and across populations, seems to have established an association between higher blood pressure and increased sodium excretion:
Within population analyses, individual 24 hour urinary sodium excretion higher by 100 mmol (for example, 170 vs 70 mmol, = approx. 2.3g) was associated with systolic/diastolic blood pressure higher on average by 3/0 to 6/3 mm Hg (with and without body mass in analyses)
A closer look at the data unveils that the BMI-adjusted data for the younger cohort is weaker than the conclusion lets us believe (1.8 mmHg increase in systole and 0.9 decreases in diastole for every 2.3g increase). But what the data also seems to show us is that the older cohort is exponentially worse at handling higher sodium loads than the younger population, possibly making a case that increased sodium worsens age-related increases in blood pressure.5 Nevertheless, what is absolutely clear is that BMI is a massive confounding factor and one that should be dealt with when planning interventions.
The impacts of reducing sodium have also been studied in combination with dietary modifications. In Effects on Blood Pressure of Reduced Dietary Sodium and the Dietary Approaches to Stop Hypertension (DASH) Diet investigators compared the standard American diet with different controlled levels of sodium to the so-called “combination diet” (=DASH), with different levels of sodium.
The combination diet was rich in fruits, vegetables, and low-fat dairy foods and had reduced amounts of saturated fat, total fat, and cholesterol. This diet provided potassium, magnesium, and calcium at levels close to the 75th percentile of U.S. consumption, along with high amounts of fiber and protein.6
The results of this investigation speak strongly for the reduction in sodium intake, with some key findings to consider especially:
The reduction of sodium intake significantly lowered systolic and diastolic blood pressure in a stepwise fashion, with both the control diet and the DASH diet
The level of dietary sodium had approximately twice as great an effect on blood pressure with the control diet as it did with the DASH diet
The DASH diet, as compared with the control diet, resulted in a significantly lower systolic blood pressure at every sodium level and in a significantly lower diastolic blood pressure at the high and intermediate sodium levels
Reducing the sodium intake from the high to the low level, with either the control diet or the DASH diet, reduced systolic blood pressure in participants with and in those without hypertension
As compared with the combination of the control diet and a high level of sodium, the combination of the DASH diet and a low level of sodium lowered systolic blood pressure by 11.5 mm Hg in participants with hypertension, by 7.1 mm Hg in participants without hypertension, and by 6.8 mm Hg in men and 10.5 mm Hg in women
Let’s dig a bit deeper into the results of this investigation. There were 412 participants recruited for this investigation, of which circa 95% completed the study. This implies good compliance, possibly demonstrating good tolerability to lower sodium intake and easy adherence to the intervention diet. 412 participants are not that much though, and might not be fully representative of the general population.
Participants were assigned to eat either the standard American diet (SAD) or the DASH diet. Within either diet, the participants were assigned to eat low, intermediate, or high levels of sodium for 30 days, in random order, i.e. some people ate high, intermediate, low; some ate low, intermediate, high; some ate intermediate, high, low, and so on.
Some problems that might arise from a set-up like this are that people certainly know what diet they are eating.7 It undermines the difference in results between diets rather than salt intakes but is nevertheless something to consider. Secondly, people on the DASH diet were eating 3x as much potassium, magnesium, and calcium, as the people assigned to the SAD. This is something I'll bring up a bit later but has certainly attributed to the difference in results between the diets. The same holds true for fiber which the DASH diet includes 3x vs. the SAD (31g vs. 9g).
One might argue that yes, that IS what makes the DASH more healthy than the SAD, and I’d certainly agree, but since we’re looking at sodium and BP, the argument seems to be that sodium is what makes a diet either good or bad for BP, even though these other components might play at least some role.
Another issue, which might be my biggest criticism of this study, is the average BMI of the participants. An average BMI of 29-30 is classified as borderline obese (>30 = obese, >25 = overweight). We know that even a slight elevation in BMI, i.e. being slightly overweight, is highly correlative to increased blood pressure and hypertension. What’s more is that insulin resistance, a phenomenon that far exceeds the development and is ultimately the cause of type 2 diabetes8, is almost certainly manifesting itself in people who are even slightly overweight.9 We know that insulin resistance at the level of the kidneys causes changes contributing to hypertension and sodium retention, which is why we might observe the beneficial effects of lowering sodium in the study.10 That is all to say that the effects of lower sodium intake on blood pressure in healthy, lean, insulin-sensitive individuals might not be as significant, as when compared to overweight and obese participants.
In general, though, the setup and methods are rigorous.11 The high-sodium SAD group vs. the low-sodium DASH group had on average 11.8 mmHg higher systolic BP, which translates to an approx. 2-3x higher risk of MACE over a lifetime. The investigators seemed to control for most modifiable variables, such as changes in weight, other electrolytes, and so on, which strongly indicates that the two factors influencing blood pressure are the "quality" of the diet and the amount of sodium. The difference in systolic BP between the high vs. intermediate vs. low sodium DASH groups was -1.3 mmHg and -1.7 mmHg, totaling a difference of -3 mmHg between the high and low DASH groups. The differences in the SAD groups were -2.1 mmHg for the high vs. intermediate and -4.6mmHg for the intermediate vs. low, totaling a delta of -6.7 mmHg, which is substantial.
What I find so perplexing about this subject is the discordance between the amount of sodium that seems to be optimal based on the Urinary Sodium and Potassium Excretion and Risk of Cardiovascular Events mentioned earlier and both crossover and randomized trials. The observational data looking at events and mortality seems to suggest that an intake of no less than 5 grams of sodium (i.e. 12ish grams of salt) is optimal. In Effects on Blood Pressure of Reduced Dietary Sodium and the Dietary Approaches to Stop Hypertension (DASH) Diet both SBP and DBP were more desirable at increasingly lower levels of sodium intake, going from 3.3 grams to 2.5 grams to 1.5 grams of sodium. Quite a few meta-analyses of trials and prospective studies have also concluded that increasingly lower intakes translate to reduced BP and projected MACEs, even in children.1213 14 This discordance doesn't seem to be explained by differences in potassium intake either.
So what might be causing the differences? If the observational data is indicating that 5 grams of sodium is optimal vs. the trials showing benefits when moving from 3 grams lower, something doesn’t really make sense.
Michael H. Alderman argues in his critique Reducing Dietary Sodium: The Case for Caution that…
…modification of this single surrogate [sodium excretion] end point does not guarantee a health benefit as measured by morbidity or mortality. Instead, they note that salt restriction capable of reducing blood pressure also unfavorably affects other cardiovascular disease surrogates.
Surrogate markers, such as blood pressure, are not clinical events, but usually are associated with the incidence of subsequent stroke, myocardial infarction, kidney dysfunction, or heart failure. Multiple randomized clinical trials (RCTs) have established that reduction of sodium intake sufficient to lower blood pressure also increases sympathetic nerve activity, decreases insulin sensitivity, activates the renin-angiotensin system, and stimulates aldosterone secretion. The health effects of sodium reduction will be the net of these conflicting effects.
We actually have a meta-analysis pointing to at least some of these “unfavorable” effects of lowering sodium intake, especially in normotensive, healthy individuals. In Effects of Sodium Restriction on Blood Pressure, Renin, Aldosterone, Catecholamines, Cholesterols, and Triglyceride: a meta-analysis investigators looked at surrogate markers of exactly the things Alderman points to.
In plasma [of normotensive individuals], the renin level increased 3.6-fold, and the aldosterone level increased 3.2-fold; the increases were proportional to the degree of sodium reduction for both renin and aldosterone. Body weight decreased significantly, and noradrenaline, cholesterol, and low-density lipoprotein cholesterol levels increased. There was no effect on adrenaline, triglyceride, and high-density lipoprotein cholesterol.
The increase in renin and aldosterone clearly speaks to an activation of the RAA system, described in Vaguely on Salt. What seems to be known from trials of ARBs and ACEis is that inhibiting the RAA system is health-promoting, and especially that over-activation of it is detrimental to health. Moreover, the investigators observed a decrease in weight, but an increase in stress-related hormones, total cholesterol, and LDL-c, which isn’t really desirable. Meaningful? I don’t know. The stuff the meta-analysis looks at is extremely hard to draw pragmatic conclusions from, especially when the outcome-oriented literature is so conflicting. Furthermore, the meta-analysis should be scrutinized harder than I’m willing to do now, so we’ll take the author’s words as stated. But just so you, the reader know, I haven’t looked hard into the methods, etc of the investigation.
Alderman also points out the inherent limitations of observational studies, which have come to conflicting results, and the limited availability of randomized controlled trials.
Actually, the point of blood pressure only being a surrogate marker and not being fully representative of clinical events is important to take note of. The medical community, myself included, seems to be of the opinion that high BP is bad independent of the reason for it. The MR data seems to confirm this, as do the RCTs done on pharmacological interventions for hypertension. But what if the etiology of the high BP matters? Maybe reducing salt intake in someone whose core reason for high blood pressure is stress-related might actually do them more harm than good, even though their blood pressure would decrease. We cannot know this not to be true. Maybe the desirable effects of pharmacological interventions do not only work by reducing blood pressure but have pleiotropic (which they certainly do have) effects that account for many of the benefits with regard to outcomes. I’d need to look at the data on the pharmacological agents, as well as observational data on BP and MACEs to even come to a start on this hypothesis, so we’ll leave it for now, but it might be worthwhile to tackle.
So what about potassium? Physiologically we know potassium plays a key role in regulating sodium excretion15, but as mechanisms do not necessarily translate to macro-outcomes, let's turn to some reviews on the subject.
A systematic review and meta-analysis, Potassium Intake and Blood Pressure: A Dose‐Response Meta‐Analysis of Randomized Controlled Trials, included 32 studies investigating the impact of potassium intake on blood pressure. The studies included summed up a total of 1764 participants with ages ranging from 18 to 79 and different ethnic backgrounds.
“Most [studies] were conducted in participants with hypertension, in 6 of which prior treatment with antihypertensive medication (mainly β blockers, thiazide, or calcium channel blockers) was continued during the trial, whereas 4 trials were restricted to participants without hypertension”. This is of course a challenge with this review, as increased potassium intakes might lead to different outcomes in hypertensive people, and certainly does lead to different outcomes in people who are on antihypertensive medications.
So what did the investigators conclude?
…we found that mean SBP and DBP levels decreased in the supplemented group with increasing differences in potassium excretion, up to a value of ≈ 30 mmol/d. At higher levels of supplementation, the decrease in BP was reduced, up to approximately a net difference in urinary potassium of 80 mmol/d.
Increases of 30, 60, 90, and 120 mmol/d in net urinary potassium excretion differences between the supplemented and unsupplemented participants resulted in SBP changes of −3.3 (95% CI, −4.9 to −1.6), −2.0 (95% CI, −3.4 to −0.5), 1.1 (95% CI, −2.9 to 4.7), and 4.2 (95% CI, −2.3 to 10.6) mm Hg, respectively. For DBP, the corresponding changes were −2.3 (95% CI, −3.8 to −0.7), −1.3 (95% CI, −2.8 to 0.1), 0.86 (95% CI, −2.9 to 4.6), and 3.1 (95% CI, −3.5 to 9.7) mm Hg, respectively.
These results seem to suggest that on average, increasing potassium intake by around 30 mmol/d would result in significantly lower blood pressure. It’s important to realize here that the increases in BP observed with higher doses of potassium have confidence intervals crossing 0, i.e. some people experienced an increase and some a decrease in BP with higher doses.
The authors go on to investigate how these results would translate over to the total daily urinary excretion of potassium:
The SBP and DBP change remained constant in the range of 90 to 150 mmol/d (3500 - 5860 mg/d) of achieved potassium excretion. Below these ranges of achieved potassium excretion, the intervention effects on BP were unfavorable, and a weak BP increase also appeared to occur at >150 mmol/d.
A potassium excretion of 30, 60, 120, 150, and 180 mmol/d resulted in SBP changes of 9.1 (95% CI, 4.6–13.5), 3.9 (95% CI, 2.1–5.8), −0.9 (95% CI, −1.6 to −0.2), −0.2 (95% CI, −2.2 to 1.8), and 0.7 (95% CI, −2.9 to 4.2) mm Hg, respectively, compared with the SBP associated with an excretion of 90 mmol/d. The corresponding DBP changes were 5.3 (95% CI, 0.9–9.7), 2.3 (95% CI, 0.5–4.1), −0.4 (95% CI, −1.5 to 0.7), 0.2 (95% CI, −3.0 to −3.3), and 0.8 (95% CI, −4.6 to 6.2).
So it’s quite clear from this data that lower potassium intake is detrimental to blood pressure. We can observe that an intake (assuming equilibrium) of 120 and 150 mmol/d results in marginally lower BP compared to 90 mmol/d, but that the benefits seem to reverse when intake exceeds 150 mmol/d (5860 mg/d).
What’s more, is that the investigators looked at the difference in effects between hypertensive and non-hypertensive participants, as well as participants on antihypertensive mediations vs. not:
Considering the effects of achieved potassium excretion according to hypertension status and using 90 mmol/d as the reference value, in those in the normal BP category, we observed increasing BP levels for decreasing potassium exposure below the reference value, whereas >90 mmol/d DBP slightly increased while this did not occur for SBP. In participants with hypertension, the range of 90 to 120 mmol/d was associated with the lowest BP values, whereas above and much more strongly below this range, both SBP and DBP increased.16
For the increased BP levels following high amounts of potassium supplementation in participants with hypertension, it was considerably more evident in those receiving pharmacological treatment (starting at ≈ 60 mmol/d of difference in potassium excretion for the supplemented participants) compared with their counterparts not taking medications, for whom the BP increase started to occur at ≈ 110 mmol/d of excess potassium excretion.17
So, as I stated earlier, the results between non-hypertensive vs. hypertensive people, and people taking antihypertensive medications vs. not are different. That’s why it’s absolutely crucial to understand that recommendations for intake cannot be generalized for people with pre-existing blood pressure issues, something that seems to be lost for many advocates of salt reduction.
Let’s lastly look at one of the most important parts of the review, namely, the effect of higher potassium intake in concordance with different intakes of sodium. For me, this is the most important part of the investigation:
Dose‐response analyses stratified by increasing level of baseline sodium excretion showed that potassium supplementation had different effects on BP values, according to level of sodium excretion
Both the lowering and the enhancing effects on BP induced by potassium supplementation were much weaker in the bottom category of sodium intake, <3000 mg/d, particularly for DBP, whereas in the intermediate category of sodium exposure, the threshold from shifting from a BP‐lowering effect into a BP‐enhancing effect was ≈ 80 mmol/d of supplemental potassium excretion for SBP and 60 mmol/d for DBP.
The highest category of sodium exposure showed the largest decrease of both SBP and DPB, with no evidence of any BP increase, even for the highest amount of potassium supplementation
The takeaway from these results is that people who consume plenty of sodium better have their potassium intake optimized. We clearly observe that potassium has the most to offer in terms of BP lowering in the context of higher sodium intakes and that the undesirable impact of higher potassium intake is limited to lower and intermediate intakes of sodium.
What I’m left wanting to know is the absolute blood pressure values for the different sodium groups. If the group with high sodium intakes had significantly higher BP at the outset, the results aren’t that interesting. Conversely, if there’s no evident difference in BP between the sodium groups at the outset, the results speak for what I’m about to conclude next. But before that, let’s briefly take a look at a few more studies and their findings.
At the outset mentioned observational study looking at sodium and potassium excretion did not find a statistically significant reduction in MACE, excluding stroke, with increased potassium intake.
There was no significant association between potassium excretion and CV mortality, MI, and hospitalization for CHF
Compared with an excretion of less than 1.5 g per day, higher potassium excretion was associated with a reduced risk of stroke (4.7% [HR, 0.77; 95% CI, 0.63-0.94] for 1.5-1.99 g/d; 4.3% [HR, 0.73; 95% CI, 0.59-0.90] for 2-2.49 g/d; 3.9% [HR, 0.71; 95% CI, 0.56-0.91] for 2.5-3 g/d; and 3.5% [HR, 0.68; 95% CI, 0.49-0.92] for 3 g/d) on multivariable analysis
But the authors go on to point out that:
Although we did not observe significant interaction between potassium and sodium excretion, the lowest CV event rates occurred in the group with moderate sodium excretion and high potassium excretion. Participants with higher potassium excretion reported higher daily intake of fruit, but the association between potassium excretion and stroke remained significant after adjusting for fruit intake.
Based on the table it certainly looks like any way you move from the moderate sodium/high potassium intake, events increase.
Another review on this subject of potassium concluded the following:
Most published studies confirmed a BP-reducing effect of potassium intake by consumption of more fruits and vegetables, salt substitutes and enrichment, or supplementation, and these studies suggest that it also plays a cardioprotective role. The BP-lowering benefit has been reported in normotensive and hypertensive individuals.
High potassium intake, rather, may have the greatest effect when salt intake is high because potassium supplementation did not reduce BP in hypertensive men also maintained on a low-salt diet.
In addition to BP reduction, dietary potassium supplementation improved measures of endothelial function, vascular adherence, and cardiovascular structure and functional parameters.
So the data on potassium really speaks for itself. But how should we tie this all into one useful conclusion? The data on sodium is really messy and conflicting, and we really don’t know if changes in surrogate markers with increased potassium intake translate to decreased events, which is what we ultimately care about. After thinking about this for some time, looking at the literature, and listening to different opinions, I think I’ve come to a sound conclusion. But my confidence interval on this is quite large, so take it all with a grain of salt (no pun intended).
First of all, the best thing anyone can do for their blood pressure and cardiovascular mortality risk is to maintain healthy body weight, exercise regularly and enough, not smoke, not consume too much alcohol, maintain emotional resiliency, reduce stress, sleep enough, not being sedentary, and so on. The data on diet is so messy that I’m not going to go there, but I’ve previously written about my framework, so there are some ideas. Everyone needs to find what works best for them in the context of their own life and preferences, which means that if there’s an issue, you try to change your dietary pattern to see if that resolves the issue, but maintain agnosticism towards specific dietary choices. We have a lot of surrogate markers to look at when assessing if specific dietary choices are “working”, so that’s something to look at.
So what about salt and potassium then? Let’s remember that these “optimizations” come secondhand after the things I just mentioned, and apply only to completely healthy people. Reducing sodium intake seems really beneficial for people who have kidney diseases or heart failure, but that is not whom this post is for.
The first thing is to consume enough sodium. The observational data seems to suggest that a range of 4-6 grams of sodium is optimal, but who knows what’s right for the individual? I assume that going lower wouldn't be dangerous, but it makes mechanistically sense that it might cause issues in the long run. With this in mind, I would also consume high amounts of potassium. The literature is suggesting that up to 6 grams would be safe, but again, one needs to find their own optimum. A diet high in fruits, vegetables, low-fat non-processed meats, potatoes, and legumes is going to have high amounts of potassium.18 I’d also be cognizant of getting enough calcium and magnesium and drinking enough water throughout the day.
What’s actually most important in my mind is to regularly monitor one’s blood pressure. Some people’s blood pressure is highly salt sensitive, which can be tested by measuring one’s BP after meals, and there are some postprandial elevations, it might indicate salt sensitivity. I’d say that consuming salt liberally, maybe to taste, and being cognizant of getting high amounts of potassium is the way to go. On top of that regularly monitoring one’s BP to see that there’s nothing to worry about. If one’s BP is elevated (assuming metabolic health is fine), I’d be rigorous in my tracking of sodium and potassium intake to establish a baseline. I’d then try to add a bit of potassium, and also maybe supplement with magnesium. If that doesn’t help, reducing sodium might be the way to go. The intake ranges observed in the meta-analyses could be used to give some direction.
Thank you for reading this far. I want to remind you that nothing in this post should be construed as medical advice. If you have any worries about your health, please don’t hesitate to visit a healthcare professional.
Regards,
Daniel
I.e. people who are assigned to the DASH diet might know that the diet is “healthy”, which would impact their blood pressure vs. people eating the SAD.
Dose‐response meta‐analysis of changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels (as mm Hg), according to achieved potassium excretion levels between arms at the end of the trials in participants with no hypertension (N=5) and with hypertension (N=27). [Source]
Dose‐response meta‐analysis of changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels (as mm Hg), according to achieved potassium excretion levels between arms at the end of the trials in participants with hypertension not taking antihypertensive medications (N=22) and using antihypertensive medications (N=6). [Source]
https://fineli.fi/fineli/fi/elintarvikkeet?component=2192&sortByColumn=component&sortOrder=desc&offset=0