Glossary

We talk about alcohol metabolism when alcohol is absorbed into the blood from the gastrointestinal tract by passive diffusion. On consumption, a small amount of alcohol is absorbed in the mouth and stomach but most of the absorption takes place in the small intestine. Usually 30–45 minutes after consumption the absorption of alcohol is at its maximum. The blood alcohol concentration (BAC) reached depends on several factors:

• the amount consumed
• the rate at which the amount is consumed
• gender
• body mass
• recent food intake and
• type of alcoholic beverage consumed.

The BAC reaches higher levels when both larger volumes of alcoholic beverages or higher alcohol percentage (ABV) are consumed. Alcohol is distributed from the blood into all tissues and fluids throughout the body in proportion to their relative content of water.

When drinking the same quantity of alcohol women usually reach a higher BAC level than men mostly because of their overall lower percentage of body water and higher percentage of body fat and average lower body weight compared to men. Similarly lean body mass and total body water is reduced in elderly individuals compared to younger individuals leading to a relatively higher BAC (= Blood alcohol concentration).

Another important factor in predicting a person’s BAC level is recent food intake. The same amount of alcohol can produce a BAC as much as 50% lower in a person who has recently eaten compared with a person who is drinking on an empty stomach.  The balance between the absorption and breakdown of alcohol determines how the BAC changes over time. Most of the alcohol is metabolised for elimination by the liver. As described earlier alcohol elimination is typically driven by specific alcohol-metabolising enzymes: alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH).  This enzyme system however becomes saturated at relatively low concentrations of alcohol.

Therefore during periods of heavy and binge drinking the liver’s microsomal ethanol oxidizing system (MEOS) an alternative pathway of alcohol metabolism gets involved and breaks down the excess ingested ethanol to help clear the ethanol faster from the body. During this process however free radicals (very reactive oxygen molecules) are created which can damage the cells of the liver (Cederbaum 2012).

Apoptosis is a type of cell death in which a series of molecular steps in a cell lead to its death. This is one method the body uses to get rid of unneeded or abnormal cells. Apoptosis plays a crucial role in developing and maintaining the health of the body by eliminating old cells unnecessary cells and unhealthy cells. The human body replaces perhaps one million cells per second. Too little or too much apoptosis can play a role in many diseases. The process of apoptosis may be blocked in cancer cells. When apoptosis does not work correctly cells that should be eliminated may persist and become immortal for example in cancer. When apoptosis works too well it kills too many cells and inflicts severe tissue damage. This is the case in strokes and neurodegenerative disorders such as Alzheimer's Huntington's and Parkinson's diseases. Also known as programmed cell death.

Binge drinking (consuming rapidly four or more alcoholic drinks over a short period of time) has been found to have a particularly negative impact on health (Roerecke et al 2014 Chen et al 2011). This pattern of consumption results in a rapid and relatively sustained increase in the alcohol concentration circulating throughout the body and brain (Wechsler et al 1998). Such a high blood alcohol concentration (BAC) can impact on metabolic processes in response to alcohol drinking such as the development of free radicals implicated in certain cancers (Brooks et al 2017). In these circumstances the elimination of alcohol from the body via the enzymes ADH and ALDH may not be sufficiently effective (Seitz et al 2007) and a high BAC continues to circulate until it triggers the MEOS system to switch on thereby increasing the capacity of the liver to eliminate the alcohol from the body.

Thus there is no doubt that binge drinkers have a high risk to develop cancer.

Gut microbiota is the name for the microbe population living in the human intestine.

The human gut microbiota contains tens of trillions of microorganisms including at least 1000 different species of known bacteria with more than 3 million genes. Microbiota can in total weigh up to 2 kg. One third of the gut microbiota is common to most individuals while two thirds are specific to each person. The microbiota in each intestine can therefore be considered as an individual’s identity card.

The gut microbiota:

• helps the body to digest certain foods that the stomach and small intestine have not been able to digest;
• helps with the production of some vitamins (B and K);
• helps to combat aggressions from other microorganisms maintaining the wholeness of the intestinal mucosa;
• plays an important role in the immune system performing a barrier effect;
• is key to ensuring proper digestive functioning when healthy and balanced

Inflammation is a type of nonspecific immune response that defends the body against the constant threat of microorganisms and chemical substances from the environment. All components of the gut participate in the intestinal immune response. The exchange of regulatory signals via the production of immune mediators (such as cytokines growth factors etc.) facilitates and amplifies cell interactions and/or activates inflammation. These mediators play an important role in the modulation of the intestinal immune system. Chronic intestinal inflammation primarily involves a dysfunction of the intestinal mucosa and an overproduction of the pro-inflammatory mediators.

Insulin resistance is a condition in which the body produces insulin but does not use it properly.Insulin a hormone made by the pancreas helps the body use glucose for energy. Glucose is a form of sugar that is the body’s main source of energy. The body’s digestive system breaks food down into glucose which then travels in the bloodstream to cells throughout the body. Glucose in the blood is called blood glucose also known as blood sugar. As the blood glucose level rises after a meal the pancreas releases insulin to help cells take in and use the glucose. When individuals are insulin resistant their muscle fat and liver cells do not respond properly to insulin. As a result their bodies need more insulin to help glucose enter cells. The pancreas tries to keep up with this increased demand for insulin by producing more. Eventually the pancreas fails to keep up with the body’s need for insulin. Excess glucose builds up in the bloodstream setting the stage for diabetes. Many people with insulin resistance have high levels of both glucose and insulin circulating in their blood at the same time. Insulin resistance increases the chance of developing type 2 diabetes and heart disease.

Interventional studies or clinical studies are considered to provide the most reliable evidence in epidemiological research.  Intervention studies are designed to analyse the cause-effect relation examining the effect of the introduction or modification of certain elements (either medical or behavioural) in a group and evaluate whether an agent or procedure reduces the risk of developing a particular disease among individuals free from that disease at the beginning of the trial. In intervention trials investigators apply treatments to individuals and then proceed to observe the effect of the treatments on the individuals (see observational studies).

The basic idea of the Mendelian randomization is to use genetic variables as instrumental variables i.e. genes associated with an exposure (in this study alcohol consumption or alcohol metabolism) but not directly related to outcome (in this study HDL-cholesterol and other lipid parameters).  Since the genetic pattern is determined before birth it should not (at least in theory) be confounded by later lifestyle exposures or outcome variables.  Thus it allows the investigators to make causal inference.

Mendelian randomization provides an approach to addressing questions of causality without many of the typical biases that impact the validity of traditional epidemiologic approaches. While Mendelian randomization studies can provide important suggestive evidence for causal relations between risk factor (consumption of alcoholic beverages in this case) and disease outcome (blood lipid levels) they are not true experiments and are dependent on several assumptions. Evidence from randomized controlled trials when possible should continue to guide clinical decisions.

A meta-analysis is a method of summarizing the results of the same research purpose and comprehensively evaluating its combined effect. It can be an objective systematic comprehensive qualitative and quantitative statistical analysis. It has functions that improve estimates of effect construct a general review method for omitting inadequate study conclusions and reinforce the effectiveness of statistical results to yield more comprehensive and reliable study results that are more representative of the general population.

Nitric oxide is a signaling molecule produced by the body that helps the body cells to communicate. It signals the body to release more blood to the organs when needed. One of the common ways to increase the concentration of NO in the body is through exercise. While working out body muscles need more oxygen which is supplied with blood. The heart pumps with high pressure to supply sufficient blood to the muscles; the lining of the arteries releases NO into the blood in order to relax and widen the vessel wall and thus more blood can pass through. However with age blood vessels and NO-systems become inefficient due to free radicals poor diet etc. causing veins and arteries to deteriorate. It helps in supplying the sufficient amount of blood flow to the tissues and therefore allows smooth muscles to relax.

Non-alcoholic-fatty-liver-disease is defined as the presence of fat in the liver (with > 5 5% of liver cells being fatty hepatic steatosis) after the excluding secondary causes of fat accumulation in the liver (e.g. significant alcohol consumption certain medications and other medical conditions). NAFLD occurs when the liver has problems breaking down lipids causing fat to build up in the liver tissue. NAFLD is now the most common chronic liver disease in high-income countries and it is estimated to affect at least 25%–40% of the general population. It can progress from simple steatosis to non-alcoholic steatohepatitis (NASH) and hepatic fibrosis to liver cancer.

The PREDIMED study is one of the few randomized controlled trials about the Mediterranean Diet. More than 7400 individuals at high risk of cardiovascular disease were recruited and tracked in 11 study sites.

The study participants were randomly assigned to one of three groups:

1. The participants receive advice on how to follow a Mediterranean diet as well as free extra-virgin olive oil
2. The participants receive advice on how to follow a Mediterranean diet as well as free nuts
3. The control group receives advice on how to follow a low-fat diet.

The main end-points that the researchers looked for were cardiovascular events such as heart attacks strokes and deaths from cardiovascular causes.

The study was stopped early after 4.8 years of follow-up as researchers found that the participants following a Mediterranean diet supplemented with olive oil or nuts had a 30% lower risk of cardiovascular disease compared to the control group.

Pancreatitis is an inflammatory disease of the pancreas associated with inappropriate release of digestive enzymes into the small intestine to aid the digestion of carbohydrates proteins and fat as well as the release of the hormones glucagon and insulin into the blood stream. These hormones are involved in the blood glucose metabolism.

Acute pancreatitis occurs suddenly and most often resolves within several days. Most cases of acute pancreatitis are linked to gallstones. Cigarette smoking and heavy alcohol use have been associated with risk of pancreatitis.

Chronic pancreatitis occurs most commonly after an episode of acute pancreatitis and is the result of ongoing inflammation of the pancreas. Damage to the pancreas from excessive alcohol use may not cause symptoms for many years but then the person may suddenly develop severe pancreatitis symptoms including severe pain and loss of pancreatic function resulting in digestion and blood sugar abnormalities.

Polyphenols are mainly phytochemicals found abundantly in natural plant food sources. The most important food sources are fruit and vegetables green tea black tea red wine coffee chocolate olives and extra virgin olive oil. Herbs and spices nuts and algae also supply certain polyphenols. Some polyphenols are specific to particular foods (ie. flavanones in citrus fruit isoflavones in soya phloridzin in apples). Others such as quercetin are found in all plant products such as fruit vegetables cereals leguminous plants tea and wine.

Wine contains phenolic compounds (polyphenols) which give wine its characteristic colour and flavour and are produced by plants in response to fungal infection and various chemical and physical stressors especially during ripening. They are extracted from the seeds and skins of grapes during fermentation of winemaking when the juice is in contact with the grape skins and seeds. The amount of polyphenols in red wine is generally greater than in white wine because the red juice has longer contact with the grape skins during fermentation enabling more phenolic substances to be extracted into the red juice. In general red wine will be richer in phenols abundant in the skin and seeds such as anthocyanin proanthocyanidins and flavonols  whereas the phenols in white wine will essentially originate from the pulp and these will be the phenolic acids together with lower amounts of catechins and stilbenes. Average total polyphenol content measured by the Folin method is 216 mg/100 ml for red wine and 32 mg/100 ml for white wine. The content of phenols in rosé wine (82 mg/100 ml) is intermediate between that in red and white wines (see flavonoids).

A prospective study (sometimes called a prospective cohort study) is a type of cohort study or group study where participants are enrolled into the study before they develop the disease or outcome in question. The opposite is a retrospective study where researchers enroll people who already have the disease/condition. Prospective studies typically last a few years with some lasting for decades.

Study participants typically have to meet certain criteria to be involved in the study. For example they may have to be of a certain age profession or race. Once the participants are enrolled they are followed for a period of time to see who gets the outcome in question (and who doesn’t).

Participants are followed for years and data is collected on the factors of interest which might include:

• When the subject develops the condition
• When they drop out of the study or become “lost”
• When their exposure status changes
• When they die.

https://www.statisticshowto.datasciencecentral.com/prospective-study/

Proteinuria is a condition where the urine contains an abnormal amount of proteins. Albumin is the main protein in the blood. Proteins are the building blocks for all body parts including muscles bones hair and nails. Proteins in the blood also perform a number of important functions. They protect the body from infection help blood clot and keep the right amount of fluid circulating throughout the body.

As blood passes through healthy kidneys the waste products are filtered out and proteins that the body needs like albumin and other proteins are kept. Most proteins are too big to pass through the kidneys' filters into the urine. However proteins from the blood can leak into the urine when the filters of the kidney called glomeruli are damaged.

Proteinuria is a sign of chronic kidney disease (CKD) which can result from diabetes high blood pressure and diseases that cause inflammation in the kidneys. If CKD progresses it can lead to end-stage renal disease (ESRD) when the kidneys fail completely. An individual with ESRD must receive a kidney transplant or regular blood-cleansing treatments called dialysis.