Flavonoid Research: Once Called Quackery, Now Called Quality

Back around 1970, when I was in high school, I saw a few mentions of “bioflavonoids” in weight training magazines. One mention came in an article about a conversation between two guys. The first guy told the second guy that if he took vitamin C, he should also take bioflavonoids (because they had actions complimentary to vitamin C). The second guy responded: “The bio-who-zinoids???” So, these compounds didn’t occupy a prominent spot in nutrition consciousness.

Fast forward to 1982 when I was about to complete my biochemistry PhD dissertation research. I saw a paper in a somewhat obscure research journal. The research dealt with catechin, a basic version of a flavonoid family in green tea and some other foods. Two things jumped out at me. One, the “bio” prefix in front of the term flavonoid seemed to have been dropped. Second, and more importantly, the research suggested that catechin might boost a copper function that our lab studied (a function that affects blood vessel strength). I asked my major professor if I could do a short side study on catechin and copper. My supervisor said I could do the work ONLY if I used just surplus supplies (because he said that nobody cared about flavonoids). When I got good results, he didn’t want to publish them (because he didn’t want to be associated with quack ideas). However, we did publish in the fine journal Biochemical Pharmacology (1). Today, this “quack” field has become a major research area.

Although in 1982, few biomedical researchers cared about flavonoids and other polyphenols, the idea that flavonoids had health benefits was not new. Way back in the 1930s, a researcher named Albert Szent-Györgyi studied flavonoids from red peppers as well as lemon juice. Dr. Szent-Györgyi had already gained notoriety for purifying vitamin C (which won him a Noble Prize). This researcher went on to find that flavonoid extracts could help repair fragile, highly permeable blood capillary walls. Vitamin C didn’t have the same action in this study. However, because vitamin C does affect capillary health in other ways, the idea of a complimentary association with flavonoids was born. Dr. Szent-Györgyi decided that the flavonoid extracts must contain a vitamin; he named it vitamin P. The P stood for permeability since the flavonoid extract could impact capillary permeability.

Eventually, the vitamin idea was dropped. A vitamin has to perform functions essential for life. Flavonoids belong to a classification now called phytochemicals. These plant compounds can contribute to health, but do not perform actions absolutely essential for life. In other words, a person could survive on a low phytochemical diet. However, quality of life and longevity could be compromised. Therefore, I describe phytochemicals by saying: You can live without them, but you will live longer and better with them.

An illustration of this was shown in a study I led (2). My lab received serum samples from people on renal dialysis. These people had consumed one of three types of liquid diets for 3 weeks. These diets contained all the essential nutrients, but lacked flavonoids and other phytochemicals. We found that with all three liquid diets, after 3 weeks, an indicator of antioxidant protection capacity declined noticeably. This was not due to a drop in serum vitamin E, a classic antioxidant. In a subsequent experiment, I looked at a low phytochemical diet plus or minus addition of the flavonoid catechin. The addition produced high values for antioxidant protection capacity (3). Thus, a low phytochemical diet can compromise antioxidant capacities, but consuming a phytochemical flavonoid can produce high capacities.

So, based on what I have said so far, flavonoids can give antioxidant protection and strengthen blood capillaries and other blood vessels. However, two questions can be asked:
1. Can flavonoids do anything else?
2. Do flavonoids actions actually make any practical and important impacts on health?

To answer the first question, I can say that flavonoids and other polyphenols do have many potentially beneficial biochemical actions. Just a few examples are:
• Anti-inflammatory properties (partly due to antioxidant effects, but also due to other actions)
• Blood circulation influences
• Nervous system modulations
• Anti-cancer effects

Different flavonoids are better at some actions than others. Thus, consuming a variety of plant foods will get you a variety of flavonoids with a variety of actions. Some foods contain particularly high amounts of certain flavonoids. Here are a few examples:
• Green tea
• High isoflavone soy products
• Citrus products
• Certain spices like turmeric
• Berries

Now, to the second question: Can flavonoid actions actually affect health to a practical degree? Well, many studies have shown how these compounds can do a range of cool things in test tube systems and cultured cells. Such studies provide valuable information, but they don’t tell exactly what happens in people in various circumstances. To fill this gap, many diet survey studies have identified people with high intakes of good sources of flavonoids and other polyphenols. The studies have found that such intakes are associated with higher rates of certain good health outcomes (and with lower incidence of some bad outcomes). One of these studies saw that getting a variety of flavonoids was particularly useful (4). However, with these type studies, it’s hard to tease out the effects of flavonoids from other good properties of such diets. Also, the types of people who consume such diets may just tend to have good health habits in general. Nonetheless, the volume and diversity of the research make it likely that flavonoids do account for some of the health effects of these diets.

Other studies have had people intentionally consume foods high in flavonoids and/or other polyphenols for a period of time. For example, our lab had middle aged adults eat an apple a day for a month (5). This intervention produced a striking decrease in oxidized LDL, a contributor to hardening of the arteries. The same type of effect was seen for a high flavonoid apple extract, though the effect was not as strong. Still, this shows that flavonoids contributed to at least part of the apple lowering of oxidized LDL. A placebo extract did not produce this action. Some other studies of flavonoid extracts of foods or spices have also shown positive effects.

One limitation of such work is that so far, studies have been mostly short and small. In addition, the research has examined only certain types of people and have used a limited range of measures. Also, some studies of foods or extracts have shown only small or no effects on what was being measured. For instance, in one of my studies (6), a citrus flavonoid extract didn’t impact a measure related to oxidized LDL.

Studies that have seen little or no effect on a given measure may suffer from design limitations. For instance, these studies have usually examined just one group of flavonoids (which may not have been the right group for a given measure). Also, the biggest responses to flavonoids may need help from other phytochemicals plus a good intake of certain essential nutrients. In addition, max response to flavonoids may require combination with a healthy general lifestyle. Yet, despite these research limitations, substantial data does make a case for flavonoids health benefits. So, as we wait for more research, why not eat a variety of high flavonoid foods now?

Since I mentioned flavonoid extract supplements, you may be wondering about the merit of such supplements. As noted earlier, in our apple study, the extract didn’t do as well as the whole apples. Why the difference? Maybe it was due to whole apples having other useful food components. In addition, some studies suggest that flavonoid absorption from the digestive tract may run higher for food sources versus supplements. Someone could argue that absorption may not be needed for all the benefits. Intestinal bacteria can change the structure of ingested flavonoids into compounds that may promote health. However, for full value, the ingested flavonoids likely need some absorption.

Another concern about supplements is that many supplements are made with just one flavonoid (or mostly one flavonoid). These single, or predominantly single, flavonoid supplements can be less effective than foods with multiple flavonoids. Also, the doses of these single (or semi-single) ingredients can run high compared to the same individual flavonoid from diet. This could render these supplements not always completely safe.

Yet, despite what I just said, supplements may have utility in some situations. For example, the apple extract noted earlier, though not as potent as whole apples, did have an effect. However, the quality of flavonoid supplements really varies. The apple product just mentioned may have health and safety advantages over products with just one, or mostly just one flavonoid. Also, supplement flavonoid doses can really differ (some too low, some very high, and some about right). In addition, the concern about low absorption of flavonoids from supplements seems to depend on the supplement. For instance, my group found respectable absorption of the citrus flavonoid supplement mentioned earlier (6). Moreover, some supplement companies use various procedures to boost absorption. An example is Longvida® curcumin sold by companies like Now Foods. Enhancing absorption should improve benefits, but this may also increase the chances for problems.

So, choosing flavonoid supplements for efficacy and safety requires some discernment and caution. I will cover this topic more in my upcoming book called The Authoritative Guide to Nutritional Supplements (subtitled The Good, The Bad, and the Unknown).

One other point about flavonoids and other polyphenols is that they are being considered for drug applications. For instance, in Europe, a flavonoid drug called Daflon 500 has been used to treat venous insufficiency and other problems. Drug directions for flavonoids hold a lot of promise, but this application definitely needs more research.

In summary, eating a variety of foods and spices rich in flavonoids and other polyphenols provides a generally safe and a likely beneficial approach to promoting health. Flavonoid supplements may also sometimes have value, but use can get tricky. Flavonoid drugs represent a promising area of research.