Importance of the Vegetable and Fruit Intake for Health Based on the Relationship between Urinary Potassium Excretion and Cerebro-cardiovascular-renal Events or All-cause Mortality

Abstract

Since it is widely accepted that there is a positive correlation between the salt intake and hypertension or cerebro-cardiovascular-renal events, salt intake restriction is currently widely recommended, especially in patients with hypertension. However, salt intake restriction does not always have beneficial effects. Indeed, an excessively low salt intake has been reported to be harmful to health. While a reasonable vegetable and fruit intake reportedly decreases blood pressure, whether or not vegetable and fruit intake truly leads to reductions in cerebro-cardiovascular-renal events or all-cause mortality remains unclear. We reviewed the importance of vegetable and fruit intake for health, focusing on the relationship between urinary potassium excretion, a marker of vegetable and fruit intake, and cerebro-cardiovascular-renal events or all-cause mortality. In conclusion, vegetable and fruit intake may be essential for reducing cerebro-cardiovascular-renal events and all-cause mortality.

Introduction

Hypertension is reportedly a risk factor for cerebro-cardiovascular-renal events (1-3). Since the very famous Intersalt Study demonstrated that the 24-hour urinary sodium excretion was positively correlated with systolic blood pressure and diastolic blood pressure (4), salt intake has been considered a cause of hypertension. Therefore, salt intake restriction is currently widely recommended, especially in patients with hypertension. However, whether or not salt intake restriction always has beneficial effects remains controversial, as it has been reported that an excessively low salt intake is harmful to health (5,6). Therefore, appropriate salt intake restriction is ideal.

Of note, when the findings of 4 centers (Yanomamo Indians, Xingu Indians, Papua New Guineans and Kenyans) from saltless culture societies were removed from the 52 total centers evaluated in the Intersalt Study, unexpectedly, the relationship between urinary sodium excretion and systolic/diastolic blood pressure disappeared among the remaining 48 centers (4). Therefore, salt intake may not always be a cause of hypertension.

One possible reason for this may be due to the presence of both salt-sensitive and non-salt-sensitive persons (7). However, when considering the total population of a society, efforts to restrict salt intake to the lowest amount necessary for health are meaningful, as salt-sensitive persons will consequently not become hypertensive thanks to these restrictions. According to the guidelines for the treatment of hypertension, at the initial stage of treatment, nonpharmacological treatment is recommended, with salt intake restriction implemented first, followed by efforts to increase vegetable and fruit intake (8).

In actual clinical settings, doctors usually recommend salt intake restriction for patients with hypertension. However, unexpectedly, few papers have shown that such salt intake restriction actually reduces cardiovascular events (9). Furthermore, recommendations by doctors for patients with hypertension to consume more fruits and vegetables seem to be less frequent than the implementation of salt intake restrictions. Although the guidelines for the treatment of hypertension state that vegetable and fruit intake does decrease blood pressure (8), limited evidence is available confirming that vegetable and fruit intake actually decreases rates of cerebro-cardiovascular-renal events, three main events of hypertension, as well as all-cause mortality.

The present review thus considers the relationship between urinary potassium (K) excretion and cerebro-cardiovascular-renal events or all-cause mortality based on previously published reports. Based on these findings, we should actively recommend that patients with hypertension and otherwise healthy people increase their consumption of vegetables and fruits.

Anti-hypertensive Effects of Vegetables and Fruits

It is well known that a high vegetable and fruit intake helps reduce hypertension. In a randomized crossover trial (6 weeks of general food intake and 6 weeks of vegetable-rich food intake), it was reported that 58 mildly hypertensive patients showed a significant decrease in systolic blood pressure during the 6-week intake of vegetable-rich food compared with during the 6-week period of general food intake (10). Furthermore, Borgi et al. reported that 3 large longitudinal cohort studies [Nurses' Health Study (n=62,175), Nurses' Health Study II (n=88,475) and Health Professionals Follow-up Study (n=36,803)] conducted for 18-26 years demonstrated that people who consumed vegetables and fruits more than 4 times per week showed a significant reduction in the onset risk of hypertension (11). In that report, carrot, broccoli, soy-based food (including tofu), raisins and apples were particularly recommended (11).

Relationship between Urinary K Excretion and Cerebro-cardiovascular-renal Diseases or All-cause Mortality

Because vegetables and fruits contain a large amount of K, urinary K excretion (g/day) can be regarded as an indicator of their intake (12).

O'Donnell et al., studying 28,880 patients with cardiovascular disease or diabetes mellitus in the ONTARGET and TRANSCEND trials with a median follow-up of 56 months, reported that lower urinary K excretion was associated with a higher risk of stroke (Fig. 1) (5). They further conducted a prospective multicenter cohort with 101,945 participants from general populations in 17 countries, with a mean follow-up of 3.7 years, demonstrating that those with lower urinary K excretion showed higher risks of cardiovascular diseases and higher all-cause mortality than others (Fig. 2) (6).

Figure 1.

Relationship between urinary K excretion (g/day) and stroke in 28,880 patients with cardiovascular disease or diabetes mellitus with a mean follow-up of 56 months (5).

Figure 2.

Relationship between urinary K excretion (g/day) and cardiovascular events or all-cause mortality in 101,945 ordinary persons with a mean follow-up of 3.7 years (6).

We performed a prospective multicenter (15 hospitals and 29 clinics) cohort study (NOBUNAGA study) in Gifu Prefecture Japan from December 2011 to September 2016 involving 3,210 patients with hypertension under treatment with anti-hypertensive drugs and measured urinary NaCl excretion (g/day) and urinary K excretion (g/day) every 6 months to investigate the relationship between these parameters and cerebro-cardiovascular-renal events or all-cause mortality (13). We found no marked association between urinary NaCl excretion (g/day) and cerebro-cardiovascular-renal events or all-cause mortality. These results may be because the systolic and diastolic blood pressure were well controlled by antihypertensive drugs, even in patients with increased urinary NaCl excretion. In contrast, a lower urinary K excretion was significantly correlated with a higher risk of cerebro-cardiovascular-renal events or all-cause mortality (Fig. 3).

Figure 3.

Relationship between urinary K excretion (g/day) and cerebro-cardiovascular-renal events or all-cause mortality in 3,210 hypertensive patients under treatment with anti-hypertensive drugs with a mean follow-up of 3.1 years (13)

Furthermore, the Europe EPIC-Norfolk Cohort trial, performed from 1993 to 2013 (enrollment from 1993-1997), demonstrated that the increased urinary K excretion group showed a significant reduction in cardiovascular events compared with the decreased urinary K excretion group when patients were divided into three groups (decreased urinary K excretion group, middle urinary K excretion group and increased urinary K excretion group) (14). These findings suggested that K has a cardioprotective effect in addition to an effect on Na excretion (14). Recently, Sahashi et al. reported a Japan public health center-based prospective study covering a period of 20.9 years in 94,658 participants, demonstrating an inverse association between the fruit and vegetable intake and all-cause mortality, with all-cause mortality significantly decreasing by 10% in people who consumed more fruits and vegetables compared with others (15).

Vegetable and Fruit Intake and Chronic Kidney Disease (CKD)

Since the outcome of the NOBUNAGA study was the composite outcome of cerebrovascular disease, cardiovascular disease and renal disease (13), we focused on CKD in this section.

It is generally accepted that we should carefully measure plasma K levels in patients with CKD, as such levels tend to be increased in patients with CKD, which may cause arrythmia. Therefore, doctors often recommend that CKD patients avoid consuming large amounts of vegetables and fruits in order to prevent the elevation of plasma K levels. However, surprisingly, the Modification of Diet in Renal Disease (MDRD) study on 5,840 patients with CKD over 4 years demonstrated that a lower urinary K excretion was significantly correlated with a higher risk of all-cause mortality (16). Furthermore, the Coronary Artery Risk Development in young Adults (CARDIA) study, in which the association between the dietary K intake calculated from 24-hour urine collection and the development of kidney disease was investigated in 1,030 young healthy adults, demonstrated that a higher dietary K intake was associated with a lower risk of albuminuria, suggesting that a higher dietary K intake may protect against the development of kidney damage (17). In addition, it was reported that a reduced urinary excretion of K was associated with the progression of CKD [a composite of a ≥50% decrease in the estimated glomerular filtration rate (eGFR) from baseline values and end-stage kidney disease] in 1,821 patients with CKD (18). However, short-term KCl supplementation in patients with CKD was reported to significantly increase K excretion and serum K levels without affecting the eGFR or albuminuria in patients with CKD, especially in older patients and those with elevated baseline serum K levels (19). In contrast, it has been reported that dietary K intake assessed by food records was not associated with serum K levels or hyperkalemia, defined as serum K >5.0 mEq/L, in either nondialysis dependent (NDD)-CKD (n=95) or hemodialysis (HD) (n=117) patients (20). Therefore, although vegetable and fruit intake may be appropriate even for patients with CKD, care should be taken with such recommendations in older patients and those with high baseline serum K levels.

Study Limitations

Every study in this review paper was an observational study. Therefore, the mechanisms by which the vegetable and fruit intake decrease the risk of cerebro-cardiovascular-renal events or all-cause mortality remain unclear. However, these outcomes may involve the antiatherosclerotic effect of K, which is abundantly contained in vegetables and fruits, as atherosclerosis is one of the main causes of cerebrovascular disease, cardiovascular disease and renal disease. Atherosclerosis is a chronic progressive inflammatory condition. K exerts beneficial effects on the vascular wall by reducing low-density lipoprotein oxidization, vascular smooth muscle proliferation and free radical generation (21), leading to the prevention of atherosclerosis progression. In addition to K, since vegetables and fruits also contain a number of different vitamins and minerals and a high fiber content, these factors may also contribute to the beneficial effects of these food items.

Clinical Perspective

Based on the reports mentioned above, vegetable and fruit intake decreases not only hypertension but also the risk of cerebro-cardiovascular-renal events and all-cause mortality. At present, the Ministry of Health, Labour and Welfare recommends an intake of 350 g/day of vegetables. However, a national nutrition survey conducted in 2019 demonstrated that people in Japan consume only 280.5 g/day of vegetables. This value is somewhat below the target. We should therefore make efforts to consume more vegetables, along with more fruits. In the clinical setting, we should recommend that patients consume more vegetables and fruits in addition to implementing salt intake restrictions to reduce the risk of cerebro-cardiovascular-renal events and all-cause mortality. To increase the K (vegetable and fruit) intake in patients, doctors should recognize that a lower urinary K excretion is associated with a higher risk of cerebro-cardiocrovascular-renal events and all-cause mortality, they should actually measure urinary K excretion in outpatients, and doctors or nutritionists should instruct outpatients to consume vegetables and fruits more when the measured value of urinary K excretion is low. We should make an effort to increase the vegetable and fruit intake in order to reduce cerebro-cardiovascular-renal events and all-cause mortality.

The author states that he has no Conflict of Interest (COI).