Antioxidants and French Paradox

The “French Paradox” refers to the phenomenon that the moderate consumption of wine, especially red wine, is alleged to have healthy effects such as the reduction of the risk for coronary disease. [1, 2] Low quantities of alcohol and the polyphenols in the beverage are thought to be the substances causing this effect. [2] Current findings indicate that the antioxidative properties of the polyphenols — secondary plant substances — play an important role here. [3] 

Definition of Antioxidant

In its broadest sense, an antioxidant can be described as a substance that delays, prevents or repairs the oxidative damage of a target molecule (e.g. polyunsaturated fatty acids). Frequently, there is a lower concentration of the substance with the antioxidative effect than of the substance changed by oxidation. [4] 

Antioxidants as Radical Capturers

Molecular oxygen (O2) as it occurs in the air we breathe is a powerful oxidation agent. When chemically or physically activated, so-called ROS (reactive oxygen species) are produced, some of which have radical character. Radicals have one or more unpaired electrons instead of paired electrons (which stabilise the condition) and are consequently especially “reactive.” ROS are therefore highly reactive, aggressive oxygen molecules that can (for instance) damage cell structures and nucleic acids in the organism by modifying the chemical structure of the single building blocks through oxidation reactions.

Examples of ROS are “free radicals” such as the superoxide anion (O2–) and the hydroxyl radical (OH·). Hydrogen peroxide (H2O2), ozone (O3) and hydroperoxides (ROOH), on the other hand, belong to the non-radical ROS. ROS are created constantly during metabolic processes, primarily during cellular respiration in the mitochondria, but can also be produced by radiation or chemicals.

Antioxidants are antioxidation agents and act as radical capturers, i.e. they are oxidised preferentially in the presence of ROS. In this way, they act as antigens in the human organism to prevent the damage to cell membranes (lipid peroxidation), proteins, carbohydrates and nucleic acids caused by oxidants (ROS). There are various regeneration mechanisms for the consumed antioxidants so that frequently small concentrations are sufficient to protect cell systems effectively from oxidative damage.

Classification of Antioxidants

When we speak specifically about foods, ingredients with antioxidative effects can be subclassified according to various criteria. First of all, classification as either naturally occurring or synthetically added antioxidants is useful. The addition is especially relevant for foods rich in fat because lipids in the presence of oxygen are subject to lipid peroxidation, which produces aromatic, volatile compounds that cause a “rancid” unpleasant smell. Antioxidants therefore delay spoilage. [5] 

 

Natural Antioxidants

Plant and animal organisms have at their disposal various tools that prevent and counteract oxidative damage to body cells and molecules such as proteins, lipids and DNA. One group is the enzymes, the other the non-enzymatic antioxidants. [5, 6] 

The enzymes superoxide dismutase, catalase and glutathione peroxidase provide primary enzymatic protection from oxidative damage by preventing directly the formation of free radicals or by capturing any that appear. The activity of the enzymes glutathione reductase and glucose-6-phosphate hydrogenase, which has an indirect impact on radical formation (e.g. by production of the reduction agent NADPH) is classified as secondary enzymatic protection. NADPH is able to capture radicals or reactive oxygen species. [6] 

Non-enzymatic antioxidants can be classified in various subgroups according to their chemical structure. The most important groups and some representatives are described below.

Ascorbic acid (Vitamin C) and the tocopherols (Vitamin E) belong to the vitamins with antioxidative effects. The carotenoids such as ß-carotene (provitamin of Vitamin A), lycopene or lutein form another subgroup. Other groups include the enzymatic co-factors (e.g. ubiquinone 10, alpha lipoic acid), some minerals (zinc and selenium), nitrogen compounds (e.g. uric acid) and peptides such as glutathione. [5, 6] 

The phenolic compounds or the polyphenols as well, most of which have a vegetable origin, form a large subgroup of the non-enzymatic antioxidants. They break down further into various subgroups; some of the important ones are mentioned here.

Among them are the hydroxycinnamic acids such as coumaric or caffeic acid, which are also components of lignin. Phenolic acids such as gallic acid are yet another subgroup from which the hydrolysable tannins are derived. Finally, the stilbenes (e.g. resveratrol in wine) and the flavonoids belong to the phenolic compounds. Many different plant substances fall in this large class of flavonoids, including the anthocyanins (the berry and grape pigments cyanidin and malvidin), flavone-3-ols (quercetin in apples and onions), flavan-3-ols (catechin in tea) and isoflavones (genistein in soybeans).

Consumers ingest both enzymes and non-enzymatic antioxidants when they eat vegetable or animal products. The nutritional effect of the specific groups is difficult to determine because of the differences in the level of resorption and variances in the degree of breakdown in the gastro-intestinal tract.

 

Synthetic Antioxidants

Synthetic antioxidants are added to many industrially produced foods as well as pharmaceutical products to improve shelf life. These additives can be recognised by an E number with the figure 3 (e.g. E 320). These substances must meet a number of prerequisites before they can be used for this purpose. They must not show any toxicity whatsoever and should be highly effective in small quantities of 0.01% to 0.02%. Moreover, a change in the substances during the food processing is undesirable (“carry-through effect”). Frequently used representatives include butylated hydroxyanisole (BHA), butylhydroxytoluene (BHT) and dodecyl gallate. [5, 6] 

Studies indicate that synthetic antioxidants could have a carcinogenic effect, prompting a search for natural alternatives that are equally effective. [6] 

Foodstuffs as a source of antioxidants

In addition to endogenous mechanisms for the prevention of undesirable oxidation, a broad range of antioxidant substances is ingested in particular with daily food.

There are many foods and beverages that contain natural antioxidants. For instance, coffee, spices, red cabbage, pomegranates and red wine are rich in polyphenols; various types of fruit and vegetables contain high levels of carotenoids and Vitamin C; vegetable oil and nuts are rich in Vitamin E; Brazil nuts, grains and meat contain selenium; and spinach, muscle flesh and offal are sources of alpha lipoic acid.

In the battle against cancer, antioxidants are used for prevention and therapy. Significant inhibitors, for example, are the flavone-3-ol quercetin, the flavones apigenin and luteolin and the isoflavones daidzein and genistein. [7] These phenolic compounds are found primarily in foods of vegetable origin as are the essential Vitamins C and E and the trace element selenium that have antioxidative effects.

Especially in warmer climate zones, spices and herbs containing antioxidants have long been used to protect fatty foods, such as mutton. These herbs and spices include sage (Salvia sp.) and rosemary (Rosmarinus officinalis), with their antioxidant ingredients carnosole and carnosolic acid, which also contribute to the herbs bitter taste. Rheinberger Underberg is also especially rich in antioxidants because of the many different herbs used in its making. [8] 

What is the truth about the “French Paradox”?

The phenomenon known today as the “French Paradox” was mentioned for the first time in 1992. Although the level of consumption of saturated fats (from eating meat, for example) is high among the French population, observers have noted a very low frequency of cardiovascular disease. Owing to the regular, moderate wine consumption in this culture, a positive health effect, especially for red wine, was suspected. This was presumed to be caused by the polyphenols, especially the resveratrol, as well as the alcohol in the wines. [9, 10] 

First of all, studies looking for evidence of positive effects from alcohol are difficult to conduct and must be interpreted with caution. There are indications of an improvement in lipoprotein metabolism from ethanol. [11] Results cannot be isolated, but always need to be weighed in relation to possible side-effects and concomitant phenomena. Some of the negative effects increase with higher and regular consumption of alcohol and outweigh the positive effects (cf. Figure J curve [12] derived from the study of Corrao et al. [13] and confirmed by subsequent meta analyses [14]). Clear proof of a positive effect on health from alcohol is lacking. [9, 10] 

 

 

The situation is different with regard to the effect of polyphenols that are found (for example) in red wine in particular because of the way it is processed as well as in herbal spirits. [8, 11] The effects polyphenols have on the organism include interaction with cellular signal paths, the interaction with DNA and the reduction of oxidative stress. [3] A large range of positive effects on many different organ functions is said to come above all from the stilbene resveratrol. It is claimed to be anti-inflammatory, anti-proliferative and antioxidative and to prevent coronary diseases and cancer. [15] 

During the examination of the antioxidative potential of ten different herbal bitters and a red wine with a highly antioxidative effect as reference, three different tests were conducted. First, the comparison revealed that the polyphenol content of Underberg is especially high and comparable with that of red wine; moreover, the antioxidative potential is significantly higher than for the other herbal spirits. Studies of the absorption and bioavailability of the polyphenol components are not yet available, however, and are of high relevance for a comprehensive nutritional assessment. [8] 

Finally, there are studies that indicate that regular consumption of red wine does not have any fundamental impact on health condition or risk of death. [9] Critics of the “French Paradox” frequently point to socio-economic factors for their arguments. Moderate wine consumption is often related to a relaxed lifestyle with a lower level of stress. [11] In addition, moderate drinking is a sign of a higher social status, which leads to a beneficial clinical-biological profile. The distortion of the studies by regarding former drinkers as abstainers is also criticised. The number of cases of illness among non-drinkers increases substantially in comparison with moderate drinkers under this false assumption. [9] 

 

Studies showing the health effects of moderate alcohol consumption must be viewed with caution and are highly controversial.

The polyphenols found in red wine and herbal spirits, for instance, display clear antioxidative potential, however, and could possibly have a positive effect on health.

 

 

Sources

  1. Lippi, G., Francini, M., Guidi, GC. Red wine and cardiovascular health: The “French Paradox” revisited. International Journal of Wine Research, 2010, 2, S. 1-7.
  2. Böhm, M., Rosenkranz, S., Laufs, U. Das „French Paradox”. DMW-Deutsche Medizinische Wochenschrift 127.51/52, 2002, S. 2748-2756.
  3. Dávalos, A., Lasunción, MA. Health-promoting effects of wine phenolics. Wine chemistry and biochemistry, Springer New York, 2009, S. 571-591.
  4. Halliwell, B. Biochemistry of Oxidative Stress. Biochemical Society Transactions, 2007, 35, (5), S. 1147-1150.
  5. Belitz, H.D., Grosch, W. Lehrbuch der Lebensmittelchemie. Springer-Verlag Berlin-Heidelberg, 2008, S. 218-223 und 467-468.
  6. Shebis, Y., Iluz, D., Kinel-Tahan, Y., Dubinsky, Z., Yehoshua, Y. Natural antioxidants: function and sources. Food and Nutrition Sciences, 2013, 4, (6), S. 643-649.
  7. Pfaar, U., Kübler E., Gygax, D. Molekulare Regulation der Bildung und Inaktivierung reaktiver Sauerstoffspezies. Molekularmedizinische Grundlagen von para- und autokrinen Regulationsstörungen, Springer Berlin Heidelberg, 2006, S. 159-199.
  8. Imark, C, Kneubühl, M., Bodmer, S. Occurrence and activity of natural antioxidants in herbal spirits. Innovative Food Science & Emerging Technologies, 2000, 1.4, S. 239-243.
  9. Marco, B., Bertelli, A. Wine, alcohol and pills: what future for the French paradox? Life sciences, 2015, 131, S. 19-22.
  10. Chiva-Blanch, G., Arranz, S., Lamuela-Raventos, R. M., Estruch, R. Effects of wine, alcohol and polyphenols on cardiovascular disease risk factors: evidences from human studies. Alcohol and alcoholism, 2013, 48, (3), S. 270-277.
  11. Halbwirth, H. Polyphenole als Qualitätsfaktoren im Wein Polyphenols. Tagungsbericht 2013, 2013, S. 305.
  12. http://www.deutscheweinakademie.de/themen/kolumne-nachgeforscht/2017/die-j-kurve-existiert-nebenschauplaetze-wirken-zuweilen-nach/ vom 21.06.2017, Zugriff: 24.07.2017.
  13. Corrao, G., Bagnardi, V., Zambon, A., La Vecchia, C. A meta-analysis of alcohol consumption and the risk of 15 diseases. Preventive medicine, 2004, 38, (5), S. 613-619.
  14. Di Castelnuovo, A., Costanzo, S., Bagnardi, V., Donati, M. B., Iacoviello, L., De Gaetano, G. Alcohol dosing and total mortality in men and women: an updated meta-analysis of 34 prospective studies. Archives of internal medicine, 2006, 166, (22), S. 2437-2445.
  15. Weiskirchen, S., Weiskirchen, R. Resveratrol: how much wine do you have to drink to stay healthy? Advances in Nutrition: An International Review Journal, 2016, 7, (4), S. 706-718.