European Journal of Cardiovascular Medicine

Rice was the only staple food of south Indian states like Kerala, Tamil Nadu, Karnataka, etc. Tapioca was introduced to the state of Kerala by the Maharaja of Travancore, after a great famine hit the state. It was brought from South America. It quickly became the staple food of the people of Kerala.^[1] Tapioca is inexpensive and more resistant to famines and pests compared to rice.^[2] It is a popular staple food in many poor African countries also. Kerala is the only state in India where tapioca is eaten as food. In other parts of India tapioca is grown only to produce cheap commercial starch for the textile industry. Tapioca is a good source of carbohydrates, dietary fibers, vitamins, calcium, potassium, etc. It is healthier than potatoes.^[3] It is a poor man’s food. The tapioca starches are cyanogenic glucoside (linamarin and lotaustralin). The gut bacteria convert it into hydrogen cyanide.^[4] If tapioca is not processed and cooked properly, it can lead to cyanide toxicity. Tapioca is banned in many parts of the world because of the risk of cyanide poisoning.^[5] Cyanide toxicity manifests as metabolic acidosis, hypoxia, bradycardia, altered mental status, etc. In severe cases it can lead to death.^[6] Cyanide toxicity causing central nervous system (CNS) is very common in many poor African countries with tapioca as the major staple food.^[7] Incompletely processed tapioca is common in areas with less water availability. The cyanide toxicity is decreased when the diet is rich in protein and iodine. Neurological conditions associated with tapioca are myeloneuropathy, konzon, epilepsy, behavioural and emotional problems, etc.^[8]

The hydrogen cyanide formed by the gut bacteria is metabolized into thiocyanate by the liver enzyme rhodanese which transfer a sulfur from thiosulfate to cyanide and make it into the nontoxic thiocyanate.^[9] Thiocyanate is water soluble and it has a half-life of about three days.^[10] Thiocyanate compete with iodine to enter the thyroid cells. It causes increased activity of thyroid gland to overcome the competitive inhibition. Higher amount of iodine in the diet is necessary for normal thyroid functions. Thiocyanate^[11] has been used to treat hypertension from the early 1920s. The usage has been stopped due to significant cardiac and neurologic toxicity.^[12] Thiocyanate reacts with the sulfhydryl groups and produce nitric oxide (NO). NO is a powerful vasodilator.^[13] It binds to vascular smooth muscles and cause relaxation of the vascular smooth muscles.^[14] It causes vasodilation of both peripheral arteries and peripheral veins.^[15] The thyroid gland secretes the thyroid hormones. The primary function of the thyroid hormone is to maintain the optimum metabolism of all body tissues.^[16] The thyroid hormone secretion is regulated by the thyroid stimulating hormone (TSH). TSH is secreted by the anterior pituitary lobe.^[17] The major hormones secreted by the thyroid gland is the thyroxine (T4), triiodothyronine (T3). Iodine in diet is taken up by the thyroid (20%) and the kidneys (80%). The thyroid cells contain a symporter that transport sodium and iodide ion (NIS). TSH acts on the nucleus of thyroid cells and increases the number of NIS.^[18] Thiocyanate (SCN^-) is an inhibiter of iodide uptake by NIS.^[19] The minimum requirement of iodine daily for normal thyroid function is about 150 microg/day.^[20] The population of Kerala is exposed to low doses of thiocyanate therefore the dietary requirement of iodine is much higher.

This study was conducted in a tertiary care teaching hospital of central Kerala to compare the blood pressure and TSH values between hypothyroid subjects, hyperthyroid subjects with matched controls. Thyroid Stimulating Hormone (TSH) or thyrotropin levels is the most accurate way to test the thyroid functions.^[21] Morning samples are best because TSH levels peak between midnight and 8 am. There is marked increase in the number of thyroid disorders all over the world including India.^[22]

We got ethical clearance from the institutional ethical committee, the Government Medical College, Ernakulam. The study was concluded within two months from April 2016 to October 2016. Inclusion criteria was all apparently healthy subjects attending the Medicine out-patient department within the age group 18-60 years. Exclusion criteria was all subjects with history of drug intake which interfere with thyroid function or blood pressure, eg. Lithium, amiodarone, glucocorticoids, dopamine, β-blockers, etc. we obtained informed consent from all subjects. A total of 209 subjects were studied, 66 males and 143 females. They were divided into three groups based on their TSH values - hypothyroid group, hyperthyroid group and matched controls. Blood was drawn after aseptic precautions were followed using a disposable syringe and needle.^[23] The blood sample were sent to the Biochemistry laboratory of the same institution to estimate the TSH values. A third generation VITROS TSH3 assay is used.^[24] The blood pressure was recorded in the sitting posture with a manual mercury sphygmomanometer and stethoscope. The BMI was calculated after measuring the height in meters and weight in kilograms, using the formula W/H² (weight divided by height square). The data obtained was entered into Microsoft Excel sheet. The data was analyzed with the help of Statistical Package for Social Sciences (SPSS) windows version 26. The results obtained were expressed as mean and standard deviation. The mean difference between the groups were analyzed using one way Analysis of Variation (ANOVA) P value, inter group P value and Kruskal Wallis P value. ANOVA, P value of < or = 0.05 is considered significant.

Total number of subjects with normal thyroid function were 120. Total number of subjects with hypothyroidism were 54. Total number of subjects with hyperthyroidism were 35 (see Table 1). Hypothyroidism is more in older age subjects (40yrs) (see Table 2). The prevalence of thyroid disorders was higher in females (85%) (See Table 3). Chi Square: 20.668 and P value: 0.001 (Significant). The TSH values were higher in the hypothyroid group. The TSH values were significantly lower in the hyperthyroid group. The systolic BP of hypothyroid group did not show significant change compared to the normal group (P=0.288). The systolic BP comparison between hyperthyroid group and normal controls did not show significant changes (P=0.915) (see Table 4). The diastolic BP of the hypothyroid group did not show significant change compared to normal controls (P=0.270). The diastolic BP of the hyperthyroid group did not show significant changes compared to normal controls (P=0.813). The Kruskal Wallis P value for BP was found to be significant (<0.001) (see Table 5). The mean BMI among the control group was found to be about 24.10. The mean BMI in the hypothyroid group was about 27.05. This value is significant (P=<0.001). The mean BMI in the hyperthyroid group was 23.34. This value is not significant (P=0.381) (see Table 6).

The age distribution of thyroid disorders in the study population was comparable to other similar studies. The sex distribution in the above study was comparable to other similar studies.^[25] Abnormal thyroid function increases blood pressure. Hypertension is a major risk factor for cardiovascular disease. Hypothyroidism weakens the heart muscle, increases peripheral resistance, causes weight gain and obesity. All these factors contribute to hypertension. Hyperthyroidism increases the heart rate and cardiac output. Both these factors increase systolic BP in hyperthyroidism.^[26] Numerous studies comparing BP in hypothyroidism and hyperthyroidism have shown significant increase in both systolic and diastolic blood pressure.^[27] The presence of thiocyanate in the blood of this population with tapioca as staple food might be the reason that there are no significant changes in blood pressure in this study population compared to other similar studies.^[28] The prevalence of hypertension^[29] is relatively low in Kerala (8.2%) compared to neighboring states like Tamil Nadu (33.9%) or Karnataka (>20%). The unique staple food might be a major contributing factor. BMI was more in the hypothyroid group compared to the hyperthyroid group.^[30] This is comparable with similar studies. Thyroid hormone plays an important role on the basic metabolism of the body. The body metabolism is decreased in hypothyroidism and it is increased in hyperthyroidism.^[31] Decrease in metabolism causes weight gain and increase in metabolism causes weight loss. This is comparable to other similar studies.^[32] The migrant Asian Indian living in other developed countries is found to have three times higher prevalence of coronary artery disease (CAD) compared to the native population.^[33] The rising prevalence has been linked to sedentary lifestyles, unhealthy diets, obesity, etc. Returning to traditional food that has survied the tests of time is always a safe choice.^[34]

STUDY LIMITATION

This study has not been conducted in the neighboring states due to difficulty in cooperation between the different states. Each state in India has its own government, unique language, culture, food habits and traditions.

In the above study there is no significant increase in systolic or diastolic blood pressure in the hypothyroid group or hyperthyroid group compared to the matched controls in this unique study population with tapioca as a staple food. This is an important finding. This indicate that the thiocyanate prevents the increase in blood pressure in this unique study population even in subjects with thyroid dysfunction. Tapioca is protective to the cardiovascular system and traditional foods are the best for health. The thiocyanate may interfere with the thyroid function only when associated iodine deficiency. Iodine supplements are useful in this population with tapioca as staple food to protect the thyroid. According to the NITI Aayog Health Index 2021, the state of Kerala is the healthiest among the larger states of India. It has the highest life expectancy of 77.3 yrs. compared to its neighbors Karnataka (70.8 yrs.) and Tamil Nadu (73.7 yrs.).^[35]

AUTHOR CONTRIBUTIONS

Dr Sona Truman designed, analyzed and wrote the paper. Paper is approved by all the contributing authors.

CONFLICT OF INTEREST

The authors declare no conflict of interests.

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