Dietary Theobromine Research Articles

Exploring the association between theobromine intake and hepatic steatosis in young people

The incidence of non-alcoholic fatty liver disease (NAFLD) tends to be younger. And the role of theobromine in fatty liver disease remains unclear. The purpose of this study was to investigate the relationship between dietary theobromine intake and degree of hepatic steatosis in individuals aged 45 and below, using data from the 2017–2020 National Health and Nutrition Examination Survey (NHANES) and liver ultrasonography transient elastography. A total of 1796 participants aged below 45 years were included from NHANES 2017–2020 data after applying exclusion criteria. Multivariate regression and subgroup analyses were conducted to examine the associations between theobromine intake and controlled attenuation parameter (CAP), adjusting for potential confounders. Generalized additive models and two-piecewise linear regression were used to analyze nonlinear relationships. In the unadjusted Model 1 and preliminarily adjusted Model 2, there was no significant correlation between theobromine intake and CAP values. However, in Models 3 and 4, which accounted for confounding factors, a higher intake of theobromine was significantly associated with lower CAP values. Subgroup analyses in the fully adjusted Model 4 revealed a significant negative correlation among individuals aged 18–45, women, and white populations. Nonlinear analysis revealed a U-shaped relationship in black Americans, with the lowest CAP values at 44.5 mg/day theobromine. This study provides evidence that higher theobromine intake is correlated with lower degree of hepatic steatosis in young people, especially those aged 18–45 years, women, and whites. For black Americans, maintaining theobromine intake around 44.5 mg/day may help minimize liver steatosis. These findings may help personalize clinical nutritional guidance, prevent the degree of hepatic steatosis, and provide pharmacological approaches to reverse fatty liver disease in young people.

Correlation between dietary theobromine intake and low cognitive performance in older adults in the United States: A cross-sectional study based on the National Health and Nutrition Examination Survey.

Few studies have investigated the effects of dietary theobromine intake on the cognitive performance of older adults. Therefore, we investigated these effects in older adults in the United States. In this cross-sectional study, we used data (2011-2014) from the National Health and Nutrition Examination Survey. Intake of theobromine intake was obtained through two 24-h dietary recall interviews and was adjusted by energy. Cognitive performance was assessed using the animal fluency test, Consortium to Establish a Registry for Alzheimer's Disease Word Learning subtest (CERAD), and Digit Symbol Substitution Test (DSST). Logistic regression and restricted cubic spline models were constructed to evaluate the correlation between the dietary intake of theobromine from different sources and the likelihood of low cognitive performance. The fully adjusted model revealed that compared with the lowest quintile, the odds ratios (with 95% confidence intervals) of cognitive performance in the CERAD test were 0.42 (0.28-0.64), 0.34 (0.14-0.83), 0.25 (0.07-0.87), and 0.35 (0.13-0.95) for the highest quintile of total theobromine intake and that from chocolate, coffee, and cream, respectively. Dose-response relationship analysis indicated nonlinear correlations between the likelihood of low cognitive performance and die-tary theobromine (total intake and that from chocolate, coffee, and cream). An L-shaped relationship was ob-served between total theobromine intake and cognitive performance in the CERAD test. The dietary intakes of theobromine (total and that from chocolate, coffee, and cream) may protect older adults, particularly men, against low cognitive performance.

Association between dietary theobromine with depression: a population-based study

ObjectiveThe purpose of this study is to investigate the possible link between dietary theobromine intake and symptoms of depression.Materials and methodsThese results are based on the responses of 3637 people who took part in the National Health and Nutrition Examination Survey in 2017–2018. Participants' daily theobromine intake was determined using a 24-h food questionnaire from the 2017–2018 cycle. Presence of depression was defined as a score of 5 or above on the Patient Health Questionnaire. Association between theobromine intake and depression was examined using a multivariate logistic regression adjusting for several relevant sociodemographic, lifestyle and health-related factors.ResultsA total of 6903 participants were included in the study. The results of multivariate logistic regression showed a correlation between depressive symptoms and theobromine intake (OR:1.17, 95%CI:1.02–1.34).ConclusionsOur cross-sectional population based study suggests that increased theobromine intake is associated with increased risk for depression. Nevertheless, more investigations are needed to confirm our findings.

Effects of long-term treatment with dietary theobromine on rat skeletal muscles.

Plastic changes of skeletal muscles, such as hypertrophy and atrophy, are dependent on physiological activities and regulated by a variety of signaling pathways, including cyclic adenosine monophosphate (cAMP) pathway. The cAMP inducing agents, such as the β2-adrenergic agonist clenbuterol, are known to induce muscle hypertrophy, and has been reported to induce slow-to-fast transitions in rat soleus muscle. Theobromine, one of the active components of cacao, functions as an inhibitor of phosphodiesterase and increases cAMP. This study hypothesized that theobromine, like clenbuterol, can induce muscle hypertrophy and influence contractile properties. Male Wistar rats were fed a normal diet or a diet containing 0.05% theobromine for 20weeks. Using biochemical, anatomical, and physiological techniques, effects of dietary theobromine on skeletal muscles (soleus, extensor digitorum longus, plantaris, and gastrocnemius) were examined. There were no significant differences in body weight, serum levels of proteins and lipids, muscle weights, dry/wet ratio of muscle weights, mitochondrial oxidation enzyme activity of muscles, isometric contractile properties of muscles, and muscle fatigue between control and theobromine-fed rats. Quantitative analysis of mRNA, however, revealed upregulation of myosin heavy chain 2x and myogenic differentiation 1, as previously reported in clenbuterol-treated muscles. The long-term theobromine (0.05%) diet in rats had no effect in inducing muscle hypertrophy and in changing contractile properties, although it had some similar effects of clenbuterol on muscle gene expression.

Association between Dietary Theobromine and Cognitive Function in a Representative American Population: A Cross-Sectional Study.

Despite reports on neuroprotective effects of dietary theobromine intake, whether dietary theobromine has beneficial effects on cognitive function is unclear. To investigate the association between dietary theobromine and cognitive function. A cross-sectional study. Data were collected from the 2011-2014 cycles of the National Health and Nutrition Examination Survey conducted by the Centers for Disease Control and Prevention of the USA. A representative American population aged ≥60 years. L-theobromine was treated as a log transform and dichotomous form (the highest quantile vs. others). Cognitive function was measured using four tests: Consortium to Establish a Registry for Alzheimer's Disease Word Learning tests, Consortium to Establish a Registry for Alzheimer's Disease delayed recall test, animal fluency test, and digit symbol substitution test. We conducted multiple regression analyses and subgroup analyses to study the association between theobromine and cognitive performance. Basic characteristics, lifestyle factors, disease history, and nutritional intake were adjusted for in these models. A total of 2,845 participants were included in the study. The highest quantile of L-theobromine intake was positively associated with sores of delayed recall, animal fluency, and digit symbol substitution tests (β, 95% confidence interval, P: 0.11, -0.00-0.30, 0.049; 0.50, 0.02-0.99, 0.043; 1.55, 0.33-2.77, 0.015; respectively) in the fully adjusted model, but not with immediate recall score (β=0.13, 95% confidence interval -0.16-0.43, P=0.361). Subgroup analyses showed that L-theobromine intake was associated with cognitive performance in the highest quantile of caffeine intake. Daily theobromine intake was associated with cognitive performance in a large nationally representative population. However, further research is needed to corroborate our findings.

Comparative toxicities of dietary caffeine and theobromine in the rat

Caffeine, incorporated into pulverized Purina Rat Chow at a concentration of 0.5%, was fed to male Sprague-Dawley rats for 7 or 8 wk and the effects were compared with those of 0.8% dietary theobromine, fed to male rats for 7 wk. Both dietary methylated xanthines produced significant decreases in food consumption and body-weight gain when compared to their respective control groups. Food consumption of caffeine-fed rat was 57.2% of controls and for theobromine-fed rats it was 77.9% of the respective controls. Theobromine produced significant decreases in thymus weights, with caffeine producing smaller decreases. The theobromine-fed rats showed severe testicular atrophy with extensive spermatogenic cell degeneration and necrosis, while the testes of rats fed caffeine for 7 or 8 wk showed only scattered vacuolar degeneration of spermatogenic cells. Caffeine appears to be more potent than theobromine as an anorexic agent in rats, but to be equivalent to theobromine in its potential for inducing thymic atrophy and spermatogenic cell with testicular atrophy.

Effects of continuous administration of dietary theobromine on rat testicular weight and morphology

Previous studies have shown that high dietary theobromine levels fed to rats results in testicular atrophy with changes in testicular cytology. An experiment was performed to determine whether these changes in rat testes are reversible. Proven breeder male rats were fed Purina lab chow containing 0, 0.2, 0.6, or 0.8% theobromine for 49 days. At that time, unilateral orchiectomy was performed on all rats. Testicular weights in the rats fed 0.6 and 0.8% theobromine-containing diets were significantly less than those from control rats and from rats fed 0.2% dietary theobromine ( p < 0.01). The seminiferous tubules from rats fed the 0.6 or 0.8% theobromine diets showed extensive severe cellular degeneration and necrosis and contained many multinucleated cells. The interstitial tissue was edematous and there was evidence of apparent proliferation of arterioles. The rats were allowed to recover and were fed the diet without theobromine for an additional 49 days. Testicular weights of the rats given 0.6 and 0.8% dietary theobromine in the first 49-day period remained significantly below those of control rats and of rats fed 0.2% dietary theobromine ( p < 0.01). Histologically, 70 to 90% of the seminiferous tubules from the rats given the two highest dietary levels of theobromine appeared almost deplete of well-formed spermatozoa. These results indicate that the theobromine-induced testicular injury appears to be irreversible over time in the affected seminiferous tubules.

Theobromine-induced testicular atrophy: Tarka, S. M., Jr, Zoumas, B. L. & Gans, J. H. (1981). Effects of continuous administration of dietary theobromine on rat testicular weight and morphology. Toxic. appl. Pharmac.58, 76

Theobromine-induced testicular atrophy: Tarka, S. M., Jr, Zoumas, B. L. & Gans, J. H. (1981). Effects of continuous administration of dietary theobromine on rat testicular weight and morphology. Toxic. appl. Pharmac.58, 76

Short-term effects of graded levels of theobromine in laboratory rodents

Theobromine was added to the diet of mature and immature male and female rats in concentrations of 0.0, 0.2, 0.4, 0.6, 0.8, or 1.0% in diets containing 22 or 10% casein and these diets were fed for 28 days. The prominent effects of increasing concentrations of dietary theobromine were anorexia (except in female rats given the 22% casein diet), decreases in body weight in mature rats, growth retardation in immature rats and atrophy of the thymus glands in rats of both sexes and testicular atrophy in male rats. Atrophy of the thymus gland and of the testes became prominent at the 0.6% die any theobromine level. There was a progressive decrease in thymic cortical lymphocytes with increasing intake of theobromine, and at the 1% level the shrunken thymus gland was composed only of stromal cells and scattered medullary lymphocytes. Testicular changes included seminiferous tubular cell degeneration and necrosis and multinucleate cell formation with degeneration and necrosis at the higher theobromine levels. A low protein diet enhanced the severity of theobromine effects on body weight and growth and on thymic and testicular weight changes and histopathology. The daily dose of theobromine which produced retrogressive changes in weight patterns and in the morphology of the thymus in both sexes and of the testes in males was approximately 250–300 mg/kg/day in mature rats and approximately 500 mg/kg/day in immature rats. Hamsters and mice were much more resistant to theobromine than were rats. A decrease in growth and in thymic weights occurred only at the highest dose levels of theobromine and testicular and thymic changes were completely absent in hamsters. Testicular changes in mice were seen only at dietary theobromine concentrations which produced considerable mortality.

Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogonial renewal.

The kinetics of spermatogenesis in mammals are reviewed with special emphasis on the seminiferous epithelium cycle and spermatogonial renewal . 2 features of the spermatogenic process are that for a given species each step of spermatogenesis has a constant duration and that many spermatogonial stem cells enter spermatogenesis simultaneously and almost synchronously. The seminiferous epithelium composed of 5 or 6 generations of germ cells form cellular associations of fixed compositi on. Spermatids at a given step of spermiogenesis are always associated with spermatocytes and spermatogonia at given steps of development. These cellular groupings were taken to represent stages of a cycle of the seminferous epithelium. The number of stages composing the cycle vary with the species and the criteria used to characterize them. The classifications of cell associations are particulary useful in investigations of the mode of renewal of the spermatogonial population. The stem cells that belong to the Type A category may be classified as "reserve" and "renewing" stem cells. The former appear to be actively involved in the production of spermatocytes in normal adult animals but the latter initiate at each cycle of the seminiferous epithelium a series of mitoses during which they renew themselves and simultaneously give rise to "differentiating" spermatogonia. The "nodal" or key mitosis that result appear to be equivalent in type and not bivalent.