A Clinical Perspective on Colorful Berries

Conventional wisdom recognizes that increasing dietary intake of fruits and vegetables high in antioxidant activity is important for healthy living and aging. A class of fruits that is increasingly popular due to the increasing awareness of its numerous health benefits, rich nutritional value, unique organoleptic properties and diversity of formulation and marketing options, is berries. Such attributes have helped position berries as “superfruits.” Further, considerable research supports a host of health benefits:

• Antioxidant Effects: reduction of neurological aging, potential memory enhancement, reduction of oxidative stress
• Blood Vessel Protection: reduction of vascular permeability and fragility, preventing glycoprotein accumulation, stimulation of vasodilator gas nitric oxide (NO), antioxidant of peroxide and peroxinitrite free radicals
• Cardiovascular Protection: preventing oxidation of low-density lipoprotein (LDL) cholesterol, reducing plaque formation, increasing plasma's antioxidant capacity
• Eye Health: potential regeneration of rodopsin, preventing eye lens oxidation-cataracts, increasing blood flow and strengthening micro-capillary blood vessels reducing incidence of macular degeneration
• Anti-Diabetic Effects: reducing diabetic angiopathy, improving digestion of starch
• Antiviral Properties: reduction of common cold onset and/or recovery time
• Antimicrobial Effects: protection from Helicobacter pylori, reduction of re-occurring urinary tract infection, general antibacterial

Although the exact active ingredients responsible for all these health benefits in berries have yet to be determined, it has been speculated that anthocyanins are a key class of compounds present acting singly or synergistically with other constituents causing this pluralistic effect. These are present in the form of glucosides (attached with sugar moieties) either singly, as monomers, responsible for the intense red colors noted with berries, or combined (proanthocyanins), which are colorless and serve as copigments or exhibit antimicrobial activity depending on the degree of polymerization.

Anthocyanins react with atmospheric oxygen or light, which can polymerize the compounds, losing their color and causing the browning of the fruits. The actual chemical composition of various berries obviously varies; however, common constituents exist and their relative quantities among berries are as follows: water (approximately 80 percent w/w); sugars (approximately 15-18 percent, mostly fructose, glucose, pectin and fiber); fat (mostly in seeds); and small amounts of protein, minerals, vitamins and flavonoids.

Botanically, berries are fruits, meaning they originate from mature ovaries of flowers that have been pollinated. Specifically, berries originate from single flowers with one superior ovary with one or more seeds that entirely ripens to an edible pericarp. A berry then can be described as a fleshy/pulpy fruit of specific origin with embedded seeds that remain undischarged (indehiscent). Berries have been used as drug preparations in Europe for treating various inflammatory and circulatory conditions associated with vascular health, specifically for treating venous inflammation (edemas and tiredness of lower limbs), treating capillary fragility of skin and soft tissue (gum and nose bleeding) and treating acute attack of piles and circulatory disorders of the retina.

Presently, there are numerous products in the market based upon various berries that exhibit variable consistency as measured for total phenolic compounds, anthocyanin content and antioxidant capacity. Such inconsistencies have caused a lack of trust toward suppliers and manufacturers and their offerings ranging from quality (potency, purity and adulteration) of the ingredients used to finished products not meeting label claims. Such quality issues range from poor testing procedures that lack specificity for the active principles (ORAC values or total phenolic content) to outright adulteration of expensive berries, such as in the case of bilberry adulteration. Complicating the situation further is an effort by various vendors to combine several different berries into products in order to increase the spectrum of actives with the anticipation that synergistic effects may be observed making the product more effective. While this is not necessarily a bad practice, it does increase the complexity in identifying the product’s active principles.

Adding further complexity to the situation is the fact that many berries are available in a range of product forms to meet specific marketing or formulation needs. Consider cranberry, which is available as a fruit juice concentrate, fruit concentrate liquid, fruit powder, fruit concentrate powder and powder extract, just to name a few forms. This raises the question, which form is to be chosen for a clinical evaluation regarding cranberry and its specific health benefits? How can the outcomes from one clinical study using one cranberry preparation be compared with those of another clinical study that used a different preparation?

Such inconsistencies have contributed to the variable outcomes of clinical studies performed with various preparations of berries. Further exacerbating this mosaic of variables is the ever-changing chemical composition of the berries due to environmental factors such as sunlight, temperature, air quality, cultivars, fruit size and storage conditions. Nevertheless, attempts have been made to standardize berry preparations using test methodologies that are specific and can profile a range of actives looking for specific ratios among them in order to improve their consistency and efficacy. However, the adoption of such methodologies is yet to become conventional among the various vendors.

This plethora of parameters that ultimately influence the outcome of clinical studies can evidently be categorized in two classes of variables; one pertinent to human and the other to nature's intervention:

• Human Intervention
• Supplier issues (lack of trust)
• QC issues (lack of standardization or standardization to a marker not the active, nonspecific test method)
• Combination of berries in one product
• Multiple offerings of raw materials from one berry
• Variable dosing (effective dose undefined)

Nature's Diversity

• Multiple actives (anthocyanins, acids, flavonols, lectins, tannins and oils)
• Synergy of actives (increases complexity and purification can diminish the effect)
• Unknown actives
• Changes in composition of actives (highly dependent on berry's condition)

There are additional challenges in conducting clinical trials with nutritional compounds. For example, when testing for antioxidant activity of a specific berry preparation, the outcome may be different when conducted on individuals under stress compared to healthy participants. This is due to the body’s homeostasis capacity that can metabolize nutrients differently depending on the body’s stress level. In this instance, the health condition of the individual can have a direct impact on the clinical outcome and invariably producing outcomes that are contradictory. It is clear that additional precautions need be considered when undertaking a clinical study regarding a nutraceutical preparation.

For more in-depth coverage of various berries, visit the following recent articles by Dr. Papadimitrou:

• Cranberries—A Clinical Perspective
• Chokeberries—A Clinical Perspective
• Blueberries—A Clinical Perspective
• Black Currant—A Clinical Perspective
• Bilberries— A Clinical Perspective
• Elderberry—A Clinical Perspective
• Wolfberry—A Clinical Perspective