Got soda ? – got neurological disease !

Got soda ?  – got neurological disease !


Cola-induced hypokalaemia: a super-sized problem


C. D. Packer

Louis Stokes Cleveland VA Medical Center
Associate Professor of Medicine,
Case Western Reserve University School of Medicine,
Cleveland, OH, USA

Consider this curious case: a 44-year-old ostrich farmer from the Australian outback developed sudden onset of muscle weakness after returning home from an evening of kangaroo-shooting. He had difficulty in getting out of his bath and was unable to stand while waiting for help to arrive. His respiratory status deteriorated, and he required intubation and mechanical ventilation. He was found to be profoundly hypokalaemic with a serum potassium level of 1.4 mmol/l. He had been drinking 4 l of Coca-Cola per day over the past 3 years, and drank up to 10 l to slake his thirst when he went for kangaroo-shooting at night. He was advised to curtail his cola drinking, and his potassium level normalised, his weakness resolved, and he made a full recovery (1).

My own patient’s case was less dramatic, but equally puzzling. He was a 51-year-old man with chronic obstructive pulmonary disease (COPD), hypertension and idiopathic gastroparesis. Over the course of 2 years, he had persistent hypokalaemia in the 2.7–3.3 mmol/l range and complained of ongoing generalised weakness and 2–3 loose stools per day. I stopped his hydrochlorothiazide and other drugs that might cause hypokalaemia, with no effect. Oral potassium supplements did not help. Laboratory testing ruled out renal potassium wasting, which in the absence of diuretic treatment seemed to point to a gastrointestinal (GI) cause. One day he showed up at my office with a 2-l bottle of Pepsi-Cola in the basket of his electric scooter. I asked him how much he drank, and he said that he sipped it continuously, 4 l per day. He was not willing to stop drinking cola, but he did agree to reduce his intake to 2 l per day. His potassium then rose to the normal range, and his weakness improved (2).

In 2007, worldwide consumption of soft drinks reached 552 billion litres or 82.5 l per person (3). This is projected to rise to 95 l per person by 2012. In the United States, annual soft drink consumption has been estimated to be 212 l per person. Sugar-sweetened soft drinks have been shown to cause obesity, type 2 diabetes, dental decay and metabolic syndrome. They appear also to increase the risk for osteoporosis, gout, gastroesophageal reflux disease, hypovitaminosis C, albuminuria and chronic kidney disease (CKD). Case reports have linked soft drinks with secondary hyperparathyroidism, oesophageal perforation, haematuria, swallow syncope, pseudoporphyria, tongue erosions, hyponatraemia and gastritis. The only therapeutic use of soft drinks is described in a few case reports of the successful use of Coca-Cola to dissolve phytobezoars.

In their review of cola-induced hypokalaemia, Tsimihodimos et al. make a compelling argument that potassium depletion should be added to the long list of soft drink-related health problems. In the cases they describe, chronic consumption of 3–10 l of sugar-sweetened cola per day led to severe hypokalaemia, hypokalaemic myopathy, and in some cases, hypokalaemic paralysis. One patient developed hypokalaemic nephropathy and subsequent nephrogenic diabetes insipidus. In all cases, the patients’ symptoms improved, and the hypokalaemia resolved with potassium repletion and reduction or cessation of cola drinking.

The proposed mechanisms of cola-induced hypokalaemia run practically the whole gamut of electrolyte physiology. First, the large glucose load can cause both an osmotic diuresis, with increased renal potassium wasting, and hyperinsulinaemia, causing intracellular redistribution of potassium. Second, drinks containing large amounts of high-fructose corn syrup send boluses of largely indigestible fructose into the GI tract, which causes potassium wasting via an osmotic diarrhoea. Third, caffeine has been shown to cause beta adrenergic stimulation, increase Na+/K+-ATPase via cellular phosphodiesterase inhibition, and produce metabolic alkalosis, diuresis and increased renin levels, all of which may contribute to hypokalaemia. The caffeine in a few cups of coffee can lower serum potassium by as much as 0.4 mmol/l (4). Based on case reports of hypokalaemia from both caffeine-free soft drinks and caffeine products (such as coffee and tea) without sugar or high-fructose corn syrup, any or all of the above mechanisms may be at work in various individuals drinking various beverages. However, soft drinks that combine large amounts of high-fructose corn syrup with caffeine, such as regular colas, might deplete potassium stores more effectively because of concurrent osmotic and caffeine-mediated potassium wasting. With his 4 l per day Pepsi-Cola habit, my patient was ingesting 396 g of fructose, enough to cause a chronic low-grade osmotic diarrhoea, and 400 mg of caffeine, the equivalent of about seven cups of coffee.

One might argue that people who drink 3–10 l of cola per day are outliers, and that excessive soft drink consumption at this level is so rare that it is not a public health issue. The problem is that we have every reason to think that it is not rare. We know, for instance, that for the period from 1999 to 2002, the 95th percentile of soft drink consumption for US male teenagers was 83 ounces per day, and for female teenagers, 61 ounces per day (5). This means that several million US teenagers were consuming two or more litres per day. Consider, too, the marketing of the soft drink. In the 1950s, soft drinks were sold in six and 1/2 ounce bottles. Twelve-ounce cans were introduced in the 1960s, followed by the 20-ounce plastic bottle in the 1990s. Today we find 24-ounce bottles in vending machines, which have apparently become the new standard for individual servings. Two 24-ounce bottles, two standard servings, equals 1.42 l. Another new development is the popular ‘Hugo’, a 42-ounce, 410 calorie super-sized soft drink sold at McDonald’s. Two of these behemoths in a day would total a whopping 2.48 l. Then (for the very thirsty), there is the 64-ounce ‘Big Gulp’ sold at 7-Eleven stores. With aggressive mass marketing, super-sizing of soft drinks, and the effects of caffeine tolerance and dependence, there is very little doubt that tens of millions of people in industrialised countries drink at least 2–3 l of cola per day. It follows that the serum potassium levels of these heavy cola drinkers are dropping, in some cases, to dangerous low levels.

Low potassium is well-tolerated in healthy adults (6), but even mild-to-moderate hypokalaemia is believed to increase the risk of morbidity and mortality in patients with cardiac ischaemia, heart failure or left ventricular hypertrophy (7). The Heart Outcomes and Prevention Evaluation study showed that even modest hypokalaemia (serum potassium < 3.5 mmol/l) increases the likelihood of myocardial infarction, cardiovascular death and stroke in high-risk patients (8). As our heavy cola drinkers age and develop obesity, hypertension and diabetes, they will become more vulnerable to the potentially lethal effects of chronic hypokalaemia.

Another concern is that even moderate chronic cola consumption has been found to be associated with CKD. A comparison of 465 patients with newly diagnosed CKD and 467 community controls in North Carolina showed a twofold increased risk of CKD in patients who drank two or more cola drinks (16 ounces) per day (9). Chronic hypokalaemia causes increased renin levels, increased sympathetic tone and altered nitric oxide metabolism. Over time, these changes can lead to vasoconstriction, salt-sensitivity, polydipsia, polyuria and tubulointerstitial injury. This hypokalaemic nephropathy is reversible if promptly treated with potassium repletion, but in long-term cases, it can lead to chronic renal insufficiency and sometimes progress to end-stage renal disease. In the North Carolina study, it was not clear what role hypokalaemia may have played; other possible causes of cola-associated CKD include diabetes, hypertension and phosphoric acid-induced kidney stone disease.

Most government responses to soft drink health concerns have focused on protecting children from youth-targeted advertising and in-school vending machines. This same focus seems to hold in the medical profession, where paediatricians are generally more aware of the health risks of soft drinks, and probably more likely than internists to discuss them with their patients. In addition to the usual questions about alcohol, tobacco and illicit drug use, internists need to start asking their adult patients about soft drink consumption. Cola drinks need to be added to the physician’s checklist of drugs and substances (such as liquorice) that can cause hypokalaemia. More work is needed on the epidemiology of cola consumption, hypokalaemia and cardiovascular disease rates. Finally, the soft drink industry needs to promote safe and moderate use of its products for all age groups, reduce serving sizes and pay heed to the rising call for healthier drinks. The tale of the thirsty kangaroo-hunter reminds us of the wisdom of Aristotle: ‘In all things, moderation’.



The author has not received funding or honoraria from any source.


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    EDITORIAL Cola-induced hypokalaemia: a super-sized problem   C. D. Packer Louis Stokes Cleveland VA Medical Center Associate Professor of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA Email: Consider this curious case: a 44-year-old ostrich farmer from the Australian outback developed sudden onset of muscle weakness after returning home from an…