The Effects of Citric and Malic Acid Found in Pomegranate Juice on Glycaemic Response to White Bread.
Condition: Hyperglycemia, Postprandial
MeSH terms: Hyperglycemia
Study type: Interventional

Summary: 
      Research has shown that diets that give rise to a high glucose response are associated with a
      number of abnormalities like increased risk of metabolic syndrome. Metabolic syndrome mostly
      comprises of insulin resistance and glucose intolerance which gives an increased risk of type
      2 diabetes. It also gives rise to other conditions like high blood pressure (arterial
      hypertension), elevated blood insulin levels (hyper-insulinemia), elevated amounts of fat in
      the liver (fatty hepatosis) and elevated amounts of lipids in the blood (dyslipidemia). After
      type 2 diabetes become clinically apparent, the risk of cardiovascular disease also rises.
      Research has also shown that foods/drinks which raise blood glucose levels gradually (low GI)
      rather than rapidly (high GI) have health benefits which include reducing the risk of
      metabolic syndrome. Laboratory studies have shown that polyphenols found in fruits,
      vegetables and plant based foods have a positive effect on carbohydrate metabolism and can
      lower the blood glucose levels.

      Therefore a lower glycemic index diet may have benefits in terms of type two diabetes and
      heart disease management, and as a method for weight loss. There has been some research into
      the effects of pomegranate on lowering blood glucose responses both chronically and acutely.
      Mechanistic evidence suggests that this effect could be down to the organic acids found
      within pomegranate juice. 16 volunteers were fed 50 g available carbohydrate from white bread
      (109 g), and either 200 ml water (control) or 200 ml solution (test) containing citric acid
      (3.8 g) and malic acid (119 mg) the quantities that are found in 200 ml pomegranate juice
      (Biona) as analysed. Blood glucose was measured at baseline, and at 30 - 60 minute increments
      over three hours. Glucose curves were plotted, and the area under the curve was calculated
      and compared between conditions for each participant.
    

Detailed description: 
      The world health organisation has reported that over 220 million people suffer from diabetes
      worldwide and that by the year 2030, this number will be doubled. The WHO also reports that
      in 2004, about 3.4 million people died from high blood sugar. About 90% of all diabetes cases
      is due to type II diabetes. Type 2 diabetes is largely due to overweight and lack of physical
      activity characterised by high glucose levels (hyperglycaemia).

      In the human diet, the source of blood glucose is carbohydrates. Dietary carbohydrate is
      important to maintain glycaemic homeostasis and provides the most of the energy in the diets
      of most people. The control of blood glucose is a hormonal process and it is very important
      to human physiology. Hormonal processes involve the release of insulin from the β- cells of
      the pancreatic cells which stimulates the uptake of glucose after a meal, to other tissues
      either for utilisation (glycolysis) or to be stored in the liver as glycogen (glycogenesis).
      When blood glucose falls below normal, glucagon is secreted from the pancreatic α-cells and
      it promotes liver glucose production by inducing the generation of glucose from
      non-carbohydrate substrates such as amino and fatty acids (gluconeogenesis) and the
      generation of glucose from glycogen (glycogenolysis).

      When the glucose homeostasis hormonal control fails, it entails high blood glucose levels
      (postprandial hyperglycaemia) which can lead to metabolic syndrome which includes obesity,
      impaired glucose tolerance (IGT), hypertension and dyslipidemia. Disturbance of glucose
      homeostasis can also lead to other symptoms such as inflammation and oxidative stress at the
      whole body level as well as disturbances of the functionality in several organs as well as
      diabetes. Therefore, as much as carbohydrates are required in the human body as a major
      source of energy, too much in the diet can have adverse health effects especially the one
      with high glycaemic effect.

      The proposed mechanism adapted from Aston, 2006 of how carbohydrates may affect human health
      is that when there is a continual presence of high glycaemic index foods in the diet, this
      gives rise to postprandial glucose rise as well as high insulin demand to act on the high
      blood glucose levels in the blood. Postprandial glucose rise and high insulin demand may lead
      to insulin resistance which is the major component of metabolic syndrome. High insulin demand
      may also lead to β-cell failure which may also result in hyperglycaemia which is also a cause
      of insulin resistance. Insulin resistance and hyperglycaemia are risk factors for metabolic
      syndrome and diabetes type 2.

      Scientific evidence suggest that postprandial hyperglycaemia in humans has a major role to
      play in health priorities like type 2 diabetes and blood glucose control. It has been
      reported that about 90% of all diabetes cases consist of type 2 diabetes. Apart from type I
      and type 2 diabetes, there are other related conditions which include pre-diabetes (impaired
      glucose tolerance (IGT) and impaired fasting glucose (IFG) as well as metabolic syndrome
      (obesity, hypertension and insulin resistance). It has been reported that pre-diabetes and
      metabolic syndrome increases the risk of developing cardiovascular disease and diabetes
      mellitus. The glycaemic index was originally proposed with the aim of managing diabetes.
      However, recent studies have shown that the GI has potential in the prevention of type 2
      diabetes as well as in the treatment of metabolic syndrome. Research has shown that high GI
      diets are associated with increased risk of developing type 2 diabetes. More research has
      shown that high GI diet is associated with a number of abnormalities like increased metabolic
      syndrome and insulin resistance. In the same way, a low GI diet is said to improve insulin
      sensitivity but more research is needed to support this. A few studies have shown this to be
      the case. However it was observed that it was difficult to know whether this was as a result
      of improved insulin sensitivity, or improved insulin secretion or due to reduced rate of
      glucose absorption.

      Potential solution having anything in the diet that can either slow down the digestion and
      absorption of carbohydrates can help reduce the risk. Among others, two potential solutions
      are that of consumption of low glycaemic index foods or having ingredients in the diet that
      can reduce the glycaemic index of foods as well as postprandial blood glucose levels. The
      presence of inhibiting components in the diet that can reduce postprandial glucose can also
      be a solution to reducing the risk. Drugs like acarbose are currently used in some countries
      for the management of type 2 diabetes which act by inhibiting carbohydrate digestive enzymes.
      However, the use of acarbose has side effects such as nausea, flatulence and diarrhoea. It
      has been reported that polyphenols also have the potential to inhibit the rise in blood
      glucose by hindering the rapid absorption of glucose.

      A recent review has reported that research using animal models as well as a limited number of
      human studies, have shown that polyphenols and polyphenol rich foods or beverages have the
      potential to affect postprandial glycaemic responses and fasting glycaemia as well as an
      improvement of acute insulin secretion and sensitivity. Other possible mechanisms as reported
      in the review include pancreatic β- cells stimulation to secrete insulin as well as
      activation of insulin receptors, modulation of the release of glucose from the liver as well
      as of intracellular signalling pathways and gene expression.

      Another recent review concluded that it is very possible that the effects of polyphenols in
      the diet will affect glycaemic index of foods as well as postprandial glucose responses in
      humans. The two mechanisms highlighted by which this can be achieved being the inhibition of
      sugar metabolising enzymes as well as transporters. This potential action of polyphenols can
      thus be compared to that of acarbose which acts by the same mechanism and research in chronic
      intervention studies has shown that it reduces diabetes risk.

      This study was carried out as a parallel control to another study which looked at the effects
      of polyphenols found in pomegranate juice. The aim was to determine the effects of the acids
      found in the pomegranate juice on glycaemic response to bread.
    

Intervention name(s): Control; Test
Intervention type(s): Other; Other
Intervention description(s): Control will be 109 g white bread to be consumed together with 200 mL water; Test will be 109 g white bread to be consumed together with 3.819 g citric acid and 119 mg malic acid dissolved in 200 mL water adjusted to pH 3.2.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science