Joint association of urinary sodium and potassium excretion with cardiovascular events and mortality: prospective cohort studyBMJ 2019; 364 doi: https://doi.org/10.1136/bmj.l772 (Published 13 March 2019) Cite this as: BMJ 2019;364:l772
All rapid responses
Inappropriate data analysis leads to misleading results on the association between sodium and potassium intake and cardiovascular outcomes
We were surprised to see another publication of the data from the Prospective Urban Rural Epidemiology (PURE) study , in spite of its many severe methodological problems, e.g. reverse causality, inaccurate estimation of sodium and potassium intake from spot urine using the Kawasaki formula . This latest analysis purported to study the joint association of urinary sodium and potassium excretion with cardiovascular events and mortality. However, it is bizarre that the authors omitted the ratio of sodium-to-potassium, which has already been shown to be a stronger predictor of blood pressure level , cardiovascular risk , and all-cause mortality  than either sodium or potassium alone. O’Donnell et al converted the sodium and potassium concentrations of spot urine into sodium and potassium intakes using the Kawasaki formula, then categorised their participants into categories of sodium and potassium intakes, before examining each category's risk of cardiovascular events and deaths over time . This resulted in a systematic bias in the estimation of salt and potassium intake, information loss (due to the categorisation of continuous variables), creating unnecessary uncertainty. These biases are further compounded by the fact that the Kawasaki formula uses parameters such as age, sex, weight, height, and creatinine concentration , most of which are strong predictors of cardiovascular outcomes; therefore, the use of the Kawasaki formula makes it impossible to disentangle the influence of sodium, potassium, age, sex, weight, and creatinine on the association with cardiovascular risk and mortality . The authors should, at the very least, publish the sodium-to-potassium ratio and its association with cardiovascular events and mortality as these measurements would not be confounded by the other risk factors.
Many well conducted studies have clearly demonstrated that the use of spot urine by the Kawasaki formula over-estimates sodium and potassium intake at lower levels and under-estimates it at higher levels, e.g. individuals commonly have errors of more than 3 g/d sodium [7,8]. Therefore, it is wrong to use findings based on spot urine to refute the current public health recommendations on sodium and potassium intake [9,10].
Indeed, there is overwhelming evidence on the benefits of reducing population sodium intake down to the level recommended by the World Health Organization . Furthermore, increasing potassium intake brings further health gains; although unlike sodium reduction, which can be done quite easily by the food industry slowly reducing the amount of salt they add to foods, as has occurred in the UK, increasing potassium intake requires individuals to make major changes in their eating habits.
Feng J He, Monique Tan, Graham A MacGregor
1 O’Donnell M, Mente A, Rangarajan S, et al. Joint association of urinary sodium and potassium excretion with cardiovascular events and mortality: prospective cohort study. BMJ 2019;:l772. doi:10.1136/bmj.l772
2 Tan M, He FJ, MacGregor GA. Salt and cardiovascular disease in PURE: A large sample size cannot make up for erroneous estimations. J Renin Angiotensin Aldosterone Syst 2018;19:1470320318810015. doi:10.1177/1470320318810015
3 Khaw KT, Barrett-Connor E. The association between blood pressure, age, and dietary sodium and potassium: a population study. Circulation 1988;77:53–61.
4 Cook NR. Joint Effects of Sodium and Potassium Intake on Subsequent Cardiovascular Disease: The Trials of Hypertension Prevention Follow-up Study. Archives of Internal Medicine 2009;169:32. doi:10.1001/archinternmed.2008.523
5 Cook NR, Appel LJ, Whelton PK. Sodium Intake and All-Cause Mortality Over 20 Years in the Trials of Hypertension Prevention. Journal of the American College of Cardiology 2016;68:1609–17. doi:10.1016/j.jacc.2016.07.745
6 Kawasaki T, Itoh K, Uezono K, et al. A simple method for estimating 24 h urinary sodium and potassium excretion from second morning voiding urine specimen in adults. Clin Exp Pharmacol Physiol 1993;20:7–14.
7 He FJ, Campbell NRC, Ma Y, et al. Errors in estimating usual sodium intake by the Kawasaki formula alter its relationship with mortality: implications for public health. Int J Epidemiol Published Online First: 2018. doi:10.1093/ije/dyy114
8 Cogswell ME, Wang C-Y, Chen T-C, et al. Validity of predictive equations for 24-h urinary sodium excretion in adults aged 18-39 y. Am J Clin Nutr 2013;98:1502–13. doi:10.3945/ajcn.113.059436
9 World Health Organization. Guideline: sodium intake for adults and children. World Health Organization, Department of Nutrition for Health and Development 2012.
10 World Health Organization. Guideline: potassium intake for adults and children. Geneva: : World Health Organization, Department of Nutrition for Health and Development 2012.
11 He FJ, MacGregor GA. Role of salt intake in prevention of cardiovascular disease: controversies and challenges. Nature Reviews Cardiology 2018;15:371–7. doi:10.1038/s41569-018-0004-1
Competing interests: FJH is a member of the Consensus Action on Salt & Health (CASH) group, a non-profit charitable organisation, and its international branch World Action on Salt & Health (WASH) and does not receive any financial support from CASH or WASH. GAM is the Chairman of Blood Pressure UK (BPUK), Chairman of CASH and Chairman of WASH and does not receive any financial support from any of these organisations. BPUK, CASH and WASH are non-profit charitable organisations. MT has no competing interests to declare.
Re: Joint association of urinary sodium and potassium excretion with cardiovascular events and mortality: prospective cohort study
A systematic review and meta-analysis of 21 randomised controlled trials (RCTs) concluded that low-sodium salt substitutes had no effect on detected hypertension, overall mortality and intermediate outcomes.
Competing interests: No competing interests
Thank you to the authors for this thought-provoking and fascinating article. The data of morning fasting urine for 103570 people reveals that the World Health Organization (WHO’s) advice of low sodium intake (<2 g) with high potassium intake (>3.5 g) every day is infrequent, which suggests that moderate sodium intake (3-5 g/day) with high potassium intake is associated with the lowest risk of mortality and cardiovascular diseases. I think the major scientific basis is as follows: the potassium channel is a regulating selectivity filter gating mechanism of drug activation; Excessive sodium consumption is related to cardiovascular diseases; 99.2% of the global adult population from 181 countries have mean sodium intakes > 2 g/day, with reduced dietary sodium in 183 countries. WHO’s target is extremely uncommon that it is similar to a fatal difficulty of sustaining regular consumption, such as nearly 10000 kinds of health products in the Chinese market cannot solve the problem of chronic disease outbreak. Although these important results have had an impact on WHO guidelines, the development of dietary sodium intake (<2 g/day) that meets the WHO guidelines is essential.
I agree that the technology of low sodium intake (<2 g) with high potassium intake (>3.5 g) every day is not the problem, it has much more to do with system change. According to our 40 patents license of Chinese invention, we have developed a Living-Plant Dry Pulverizer, which is used to transform living plant (barley grass) directly into ultrafine powder and nutritious water in 3 minutes below 50 ºC; the cost is only 1/10 of the cost of freeze drying and half of the cost of general processing. Intracellular potassium and extracellular sodium are indispensable elements in life. This device of cell wall breaking will greatly enhance the intake efficacy of intracellular potassium in functional foods. Zeng’s review points out that more than 30 functional ingredients in barley grass exert potent preventive effects in more than 20 chronic diseases, especially major mechanism with rich in GABA, ﬂavonoids, SOD, K-Ca,vitamins and tryptophan. Potassium content (3384 mg/100g) in barley grass is 10.3 times higher than that of sodium, which prevents cardiovascular heart diseases, regulates blood pressure, increases cognition, improves sleep and so on. The average content (1825mg/100g) of potassium in barley grass for 31 cultivars that we bred is 63.8 fold higher than that of sodium when planted in the mountainous red soil; It contains 62 times GABA (327.5 mg/100g) as well as 99 times Ca and 31 times K than that of polished rice. The average content (3183 mg/100g) of potassium in barley grass for 193 RILs that we bred is 7.4 fold higher than that of sodium in crops planted in vegetable fields that often use human urine and feces.
Higher potassium intake (fruit, vegetables, nuts) is a marker of healthier food, however low potassium intake with cardiovascular risk reflects lower intake of fruits and vegetables. However fruits, vegetables and whole grains were indispensable among four top diets i.e. DASH (lower blood pressure), Flexitarian (lose weight), MIND (brain health), especially Mediterranean diet (whole grains, fruits, vegetables, beans, herbs, spices, nuts and olive oil) with significant lower cardiovascular disease and mortality. The ten healthiest countries in the world are associated with the Mediterranean diet and island effect, i.e. Spain, Italy, Iceland, Japan, Switzerland, Sweden, Australia, Singapore, Norway, and Israel, which ranks 169 economies according to factors that contribute to overall health from WHO and United Nations Population Division and the World Bank (https://www.untvweb.com/news/spain-is-2019s-healthiest-country-bloomberg/). These diets with high potassium intake are related to the African center of crop origin (Mediterranean, Ethiopia,West and Cental Africa) for Paleohuman’s foods.
Therefore in my opinion, human chronic disease outbreak due to staple foods ranging from ancient brown rice and barley with high potassium intake to modern white rice and wheat white flour with low potassium intake, which are associated with six major dietary structures from early hominids to modern humans, especially sustaining major foods + barley grass powder are the most healthy dietary guidelines for modern humans. This guide is conducive to achieving the WHO’s target of of low sodium intake (<2 g) with high potassium intake (>3.5 g) every day.
 O’Donnell M,et al. BMJ 2019;364:l772
 Schewe M, et al. Science 2019; 363 (6429): 875-880
 Webb M, et al. BMJ 2017;356:i6699
 Zeng YW, et al. Oxid Med Cell Longev 2018;2018:3232080
 Zeng YW, et al. http://science.sciencemag.org/content/363/6426/538/tab-e-letters
 Zeng YW, et al. Genet Mol Res 2016;15(4): gmr15049103
 Zeng YW. http://science.sciencemag.org/content/362/6416/762/tab-e-letters
Competing interests: No competing interests