Beyond Salt – our letter in the Lancet about salt, hypertension, and insulin.

We recently had this letter on salt and hypertension published in the British journal, The Lancet.[1] It’s unusual for the Lancet to publish favourable references to low carbohydrate diets. They tend to publish material supporting statins and fat-restricted dietary guidelines instead (thus setting up a series of controversies with the more reformist British Medical Journal. This probably helps the readership of both journals, and, by provoking open debate, generally advances the cause of science). So we’re very pleased that they thought the ideas in our letter sensible or informative enough to deserve publication.


Here we explain how we got drawn into this area, and why we think that the effects of LCHF on high blood pressure are relevant to people eating all kinds of diets.

Most people who start on a very low carbohydrate diet lose an extra pound or three or easily in the first week, and the conventional explanation is that this is nothing to get excited about as it’s water weight, water bound to glycogen that’s freed up when glycogen stores become depleted. We’ve never been happy with that explanation, because often the loss is much greater than the amount we’d expect from glycogen depletion.

In someone with hypertension, some of this water is actually part of the increased extracellular fluid volume that’s kept their blood pressure high. It’s good to be losing it.
In fact, if someone has high blood pressure, it’s very likely that they’ll be cutting down on medications quite soon after starting this diet – people with type 2 diabetes often reduce or come off blood pressure medication even before they cut down on blood sugar meds. We saw this in the very-low carb studies we reviewed for our New Zealand Medical Journal article on diabetes.

At the same time, you can start losing sodium easily, and you often need to supplement salt to keep your electrolytes in balance, when you cut carbs very low.

I’ve (GH) (and me (GS)) had this experience, getting cramps and feeling weak on a very low carbohydrate diet until I drank some water with extra salt, and I’ve also had the opposite experience of eating a salty high-carbohydrate meal in a Japanese restaurant and waking up visibly puffy from the retention of sodium and water. Such experiences are common.

The sodium (Na+) concentration in our body fluid needs to be kept within a quite narrow range, so if we’re retaining sodium we need to retain water and vice versa, and if losing, the opposite applies. And this system seems to be regulated by insulin – someone with type 1 diabetes who has no insulin will lose both electrolytes and fluid volume quickly.
So when we saw the study by Andrew Mente and colleagues in the Lancet, where most people tolerated high levels of salt long-term without increased systolic blood pressure or risk of CVD events or mortality, but in people with hypertension increases in blood pressure were associated with increasing sodium intakes, and increased CVD risk with high intakes, especially over 7 grams a day – which is a lot (in both groups low sodium intake, under 3 grams a day, was also associated with risk), we wondered whether the dietary context had an influence on this risk.[2]

We looked to see what’s known about sodium reabsorption in the kidney, and found several experiments. The experiment we cited as our reference 5[3] has a particularly brilliant design – linking it to both the glucose and insulin concentrations in the blood. We also found that it’s well-accepted that essential hypertension is part of the metabolic syndrome, along with high insulin, elevated blood sugar, high triglycerides and low HDL.
(Essential hypertension is supposedly hypertension without known cause, it “just is”.

Actually, the distinction is to contrast it with hypertension secondary to some diagnosable physiological abnormality or disease – for example, portal hypertension, when cirrhosis of the liver inhibits the removal of blood by the liver from the portal vein, or hypertension due to kidney disease and so on.)

So it seems there may be a more coherent view of hypertension which explains why it appears in the context of metabolic syndrome.

We thought it is worthwhile for researchers to assess how much hypertension is associated with elevations in the insulin response to glucose. In other words, it’s worth looking for evidence as to whether this is (as we put it in our letter) due to to their not tolerating the amount of carbohydrate in their usual diet.

Because budgetary factors are important to the chances of any large study (the study in Mente et al was huge, n=133,118), we suggested the cheapest proxy for insulin, the fasting triglyceride/HDL ratio, which correlates quite well with the 2-hour insulin response to an OGTT in people without diabetes, and which are data that are in most people’s medical records already. The use of this proxy could be validated with the 2-hour insulin response to an OGTT in a subgroup if necessary. It can be seen in this study, chosen at random, that a doubling of the HDL/TG ratio (from ~2 to ~4 here) correlates with a doubling of the 2-hour insulin level (in table 2).[4]


You can calculate the TG/HDL ratios in any study with the online calculator below and compare them with the 2 hour insulin (120′) level to see how well these correlate.

We already know that restricting carbohydrate in the diet is an effective tool for improving most cases of hypertension, but this sort of investigation would enable us to know with more certainty whether the consumption of modern high-carb diets lies somewhere on the causal pathway as well.

It’s not our position that dietary guidelines need to warn against high-carbohydrate diets – there’s no good evidence for that, they seem fine for plenty of people – but instead that they should supply clear information that restricted-carbohydrate diets are safe, and can be beneficial for weight management, blood sugar control, the management of blood pressure, and so on.

Researching this post brought up a very interesting animal study.[5] In this experiment, a naturally hypertensive breed of rat was treated with high insulin doses. This greatly increased the animals’ blood pressure over baseline, and 4 of the 8 insulin treated rats suffered heart attacks – despite having no atherosclerosis, and not being fed cholesterol and high fat diets. Animals that are given atherosclerosis with high cholesterol diets don’t usually suffer heart attacks or other adverse effects. The placebo-treated hypertensive rats, and the insulin-treated normal rats, didn’t suffer heart attacks.

Demonstrating, perhaps, that high blood pressure plus high insulin is a dangerous combination, even when cholesterol is low. The discussion section of this paper is an interesting summary of the evidence for hyperinsulinaemia as causal in heart disease.

However, nothing in biology is ever quite as simple as we’d like it to be. Fuenmayor et al in 1998 found that insulin resistance in salt-sensitive, but not salt-resistant hypertension was worsened by high salt intakes.[6] So these individuals may have an additional method to lower insulin, by avoiding high salt intakes. However high salt intake in this study was achieved by giving an extra 12 grams (3 teaspoons) of salt (4.6g sodium) a day on top of the low salt diet (this would take total intake to about 7g day), and this was not a cross-over study (7 days of low salt diet came first). Fasting and two-hour insulin in even the salt-resistant hypertensive cases was significantly higher than in non-hypertensive non-diabetics. The two-hour insulin is lower, as an artifact of the insulin suppression test used.


Fuenmayor et al concluded

Our observation is in line with the recent findings of increased insulin secretion in response to an oral glucose load in salt sensitive compared to salt resistant hypertensives. Therefore, carbohydrate administration (food intake) would induce silent hyperinsulinemia in salt sensitive patients. The elevated insulin levels may induce and worsen salt sensitivity and hypertension, and in the long term favor cardiovascular atherosclerotic complications.

Take-home message

Of course the quickest way to get too much salt and have your insulin raised too much by carbohydrate is to eat processed food. Avoid that, and it’s hard to overload on sodium just from occasional salty foods like feta, salted butter, and bacon. Use table salt (preferably iodised if you don’t eat a lot of seafood ) to taste. Have your blood pressure checked at the end of every doctor’s visit (seeing a doctor has been proven to raise your blood pressure, so only have it read once you’ve been seated for a while and have relaxed, if you can). If your blood pressure is too high, and you’re not eating heaps of salty or processed food, a LCHF diet may be a safer (and more effective) way to manage it than trying to cut salt as low as you can.

[2] Mente A, O’Donnell M, Rangarajan S et al. Associations of urinary sodium excretion with cardiovascular events in individuals with and without hypertension: a pooled analysis of data from four studies. Lancet. 2016 Jul 30;388(10043):465-75. doi: 10.1016/S0140-6736(16)30467-6. Epub 2016 May 20.
[3] Manhiani, MM, Cormican, MT, and Brands, MW. Chronic sodium-retaining action of insulin in diabetic dogs. Am J Physiol Renal Physiol. 2011; 300: F957–F965.

[4] Temelkova-Kurktschiev T, Henkel E , Schaper F, et al. Prevalence and atherosclerosis risk in different types of non-diabetic hyperglycemia. Is mild hyperglycemia an underestimated evil? Exp Clin Endocrinol Diabetes. 2000;108(2): 93-99.

[5] Zimlichman L, Zaidel S, Nofech-Mozes A et al. Hyperinsulinemia Induces Myocardial Infarctions and Arteriolar Medial Hypertrophy in Spontaneously Hypertensive Rats.
AJH 1997;10:646–653. zimlichman1997

[6] Fuenmayor N, Moreira E, Cubeddu LX. Salt sensitivity is associated with insulin resistance in essential hypertension. Am J Hypertens. 1998 Apr;11(4 Pt 1):397-402.


3 Comments on “Beyond Salt – our letter in the Lancet about salt, hypertension, and insulin.

  1. Pingback: Is Salt the Cause of Hypertension? – Health and Fitness 24

  2. Pingback: Is Salt the Cause of Hypertension? | Linda Gardner's Blog

  3. Pingback: SALT | Blaming the Wrong White Crystal - Insulean

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