Nutrients And Combinations: Fit For Purpose?

A common nutritional complaint regarding American eating habits is that the culture tends toward a mono-diet, meaning that only a handful of foods account for most of the diet. Favored foods typically include, either directly or in derived and hidden forms, corn, wheat, soy, potatoes, canola oil and a few other items along with foods based on these as feed, such as the meat, fish and fowl raised on them. There are a number of reasons for the narrowness of this range, one of the most powerful being subsidies to agriculture. Staple crops and foods are subsidized and relatively inexpensive whereas fresh fruit and vegetables along with most foods not on the favored lists of subsidies are expensive. One result is what economists term "externalities," in this case costs borne by individuals and society, such as poor health, higher medical and medical insurance costs along with shorter life spans. In contrast to the results of typical American eating habits, experience commonly demonstrates that merely increasing the range of food choices with an emphasis on fresh as opposed to canned, frozen and preserved foods can introduce considerable benefits. Similar benefits sometimes can be achieved through the proper use of dietary supplements with the catch, however, that not all supplements match the purposes for which they are being taken. (Note: some foods do well frozen, such as corn, peas and many fruits, especially berries; canning is more limited, but includes, for example, tomatoes. However, most vegetables need to start off fresh!)

Foods Rescue the Prostate

It is not necessary to consume large amounts of exotic nutrients to obtain significant benefits. In 2013 a group of British researchers performed a six month long experiment in which 203 adult males with prostate cancer consumed either a placebo or a simple supplement mixture consisting of powdered pomegranate, turmeric, green tea and broccoli.¹ Only the green tea was an extract, and even then providing roughly the same amount of actives as found in a cup or two of brewed green tea. Consumed three times a day, the active arm was comprised of:

• broccoli powder (Brassica oleracea) 100 mg
• turmeric powder (Curcuma longa) 100 mg
• pomegranate whole fruit powder (Punica granatum) 100 mg
• green tea 5:1 extract (Camellia sinensis) 20 mg, equivalent to 100 mg of crude green tea

After six months, the researchers found that prostate-specific antigen (PSA) levels, a possible marker for prostate cancer, were 63 percent lower among those taking the supplement than among those taking the placebo. This significant result was achieved with really quite tiny amounts of everyday foods and, except in the case of the green tea, these were not even extracts.

A number of studies have demonstrated that quite a range of compounds found in everyday foods are protective not just against prostate cancer, but also against many other cancers, as well. As another example, ursolic acid (found in apple peels and rosemary herb) in combination with turmeric’s ingredient curcumin or resveratrol (found in grapes and berries) blocks the uptake of glutamine by cancer cells yet do not interfere with the metabolism of normal cells—glutamine is a nutrient cancer cells need in order to grow.

Plant Colors, Plant Nutrients and Nutritional Synergy
Current government health recommendations include five servings per day of fruit and vegetables along with the suggestion that nine servings would be better. Unfortunately, this type of recommendation tends to be a bit misleading in that some fruits and vegetables are vastly more nutritious than others. For instance, cabbages in general are sources of compounds including isothiocyanates and indoles. However, cabbage-family members such as bok choy are comparatively light in nutrition compared with purple cabbage, which is rich in anthocyanidins as well as the expected precursors of sulforaphane. Similarly, leaf lettuces tend to be much more nutrient rich than is head lettuce. Below is a rough overview of some of the phytonutrients matched to associated colors in plants. There is a large degree of overlap and many phytonutrient polyphenols are almost colorless in the amounts found in foods. We tend to not associate black tea and coffee with nutrition, but the former is a source of theaflavin and the latter, if not overly roasted and freshly brewed, is a good source of chlorogenic acids.

Red—lycopene, associated with tomatoes, pink grapefruit and watermelon; anthocyanidins (cyanidin literally meaning "red color") associated with berries, other highly colored fruit, beets

Red/Purple—anthocyanidins, resveratrol and related compounds found in berries, other highly colored fruit, beets and eggplant, also found in black and other beans, black rice

Yellow/Orange—alpha- and beta-carotene, beta-cryptoxanthin; sources include carrots, citrus fruit, squashes, sweet potatoes, cantaloupes; hesperidin and diosmin are found in citrus fruit; rutin, related to hesperidin, is found in buckwheat

Yellow/Green—lutein, zeaxanthin, quercetin, catechin, epicatechins, ellagic acid, isothiocyanates and indoles found in peppers, kale, cabbage, many other green vegetables, green tea; the best single source of highly bioavailable lutein and zeaxanthin is the yolk of eggs from hens allowed to eat grass and insects

White/Green—allicin and related compounds, rutin in garlic and onions; isothiocyanates and indoles are found in cabbage family members, including cauliflower; many flavonoids; quercetin glycosides, phloretin glycoside (apple skin), chlorogenic acid and epicatechin found in "white" fruits (apples, pears), eggplant, green tea, freshly brewed coffee (chlorgenic acid)

Various polyphenols and other phytonutrients provide benefits, many of which overlap, but some of which are special to one or another family of compounds. One huge payoff from variety is that there can be unexpected synergisms. This is an issue dealt with in these pages several years ago in the article, "Beyond Synergy—the Entourage Effect in Nutrition and Herbalism." (Total Health, September 2015) It is worth repeating here a key example described in that essay.

At the 219th American Chemical Society National Meeting held in San Francisco on March 26–30, 2000 researchers associated with the company Polyphenolics presented studies that supported supplementing the diet with special plant-derived nutrients and consuming more whole fruits and vegetables. One of my associates pointed out that antioxidant vitamins are present in the human body at levels typically twenty to several hundred times the level of plant polyphenols. This is one reason that so much less research has focused on the antioxidant vitamins in foods and relatively little research has been done on the antioxidant roles of the other compounds present. By 2000, however, it already was becoming clear that these non-vitamin plant antioxidants have an impact on the antioxidant status of the body that is much beyond their representation in the blood and tissues. For instance, at the conference it was explained that an extract from grape seeds given to human volunteers led to a much greater increase in the antioxidant capacity of the subjects’ blood than was theoretically possible based on the compound alone. This was a finding that called for explanation. A second set of tests helped to clarify the result of the first—the same grape seed extract demonstrated significant synergism when tested in vitro with the antioxidant vitamins C and E, either alone or in combination.

To establish a quantitative baseline for the antioxidant power of each of the compounds, tests used the standard cupric ion generation of oxidation to look at the impact of combining our grape seed extract (Vixox Gold™) with vitamins C and E to gauge the synergy of the combinations. Vitamin C, vitamin E and grape seed extract were each tested individually to determine their effects at several concentrations. These baselines were added to yield the "Sum of Individual Inhibitions" which then was compared with the "Actual Inhibitions When Tested Together." The Actual Inhibitions minus the Sum of Individual Inhibitions times 100 yielded the percent of Synergism. This series of in vitro tests thus allowed the investigator to elegantly demonstrate the concentrations of maximal synergism amongst the three antioxidants. Strong synergism was shown for Vinox Gold™ plus vitamin C, for Vinox Gold™ plus vitamin E, and, finally, for Vinox Gold™ plus vitamin C and vitamin E.

Synergisms in the ranges shown here are good examples of why it is that consuming a diet rich in fruit and vegetables is so much more successful in terms of health than is eating a diet based on refined carbohydrates, protein and fats.

Cautionary Tales Regarding Supplements

Refining the "big three" macronutrients and then "adding back" nutrients/micronutrients loses the benefits of the plant compounds that otherwise are present in the original sources of carbohydrates and in partially refined oils, such as olive and sesame oils. Supplements are useful, but they do not take the place of fresh food properly prepared in a diet emphasizing adequate variety. Moreover, there are other reasons for being careful about the use of non-food interventions.

A good example, one that shows the overlap of how we sometimes use over-the-counter drugs and nutrients, is drawn from sports. Almost all of us, whether inclined towards athletics or not, have experience with soreness from exercise beyond our current level of physical preparation. "Weekend warriors" are familiar with this and so are high school, college and professional athletes. To overcome soreness from exertion beyond our capacity, it is common to take pain relievers. Hard physical training even in healthy you individuals, of course, is itself associated with post-exercise soreness.

To prevent this, researchers at various centers have explored whether taking aspirin or similar compounds can prevent the development of post-exercise soreness. The findings of these experiments were that taking aspirin or some other non-steroidal anti-inflammatory can, in fact, mitigate the development of soreness. That was the positive finding. The not-so-positive finding was that this approach also prevented improvements based on training or overload effects! It turned out that a certain amount of local damage to the tissues caused by overload is required to induce improvements in exercise capacity based on training.

That was a bit of a surprise even if, in scientific terms, it also was a very interesting and useful finding. More surprising still were the results of a variation on the theme of using NSAIDs prophylactically to prevent muscle pain. Researchers reasoned that tissue damage was due to, among other things, localized oxidative challenge associated with tissue damage. Instead of NSAIDs, classic powerful antioxidant vitamins and compounds were provided: vitamin C, E and N-acetyl cysteine (NAC). As was the case with the pre-workout use of NSAIDs, these antioxidants taken in quantity before training sessions did reduce soreness. Just as in the case of the NSAIDs, they also reduced the benefits of training.

More recently still, reports have emerged showing that very high dose resveratrol (250 mg) interferes with the benefits of exercise training.² This finding is not limited to resveratrol and potentially extends to quite a number of nutrients:

"support for beneficial effects of resveratrol in human [sic] is weak and studies even show that resveratrol supplementation, similarly to supplementation with other antioxidants, can counteract the positive effects of physical activity. Regular physical activity remains the most effective way of maintaining and improving vascular health status and caution should be taken regarding potential interference of supplements on training adaptations."³

It should be pointed out that such negative findings are balanced by other positive findings. In another study with older individuals 65–80 years of age, 500 mg per day resveratrol, although it did not improve cardiovascular risks compared to exercise alone, did improve the number of functional mitochondria in muscle and "subjects that [sic] were treated with RSV had an increase in knee extensor muscle peak torque (8 percent), average peak torque (14 percent), and power (14 percent) after training, whereas exercise did not increase these parameters in the placebotreated older subjects."^4,5

These findings can be reconciled in a variety of ways. For instance, one implication is that high dose resveratrol might be cycled to improve muscle quality and function, then removed from the cycle to allow for the emergence of other benefits. Those readers interested in further exploring the use of antioxidants in exercise and aging might do well to consult "Oxidative stress: role of physical exercise and antioxidant nutraceuticals in adulthood and aging."⁶

A second and more serious type of caveat emptor case involves taking a cocktail of supplements and finding that one of these undoes the benefits of the others. Several years back, a group of researchers at Georgetown University Medical Center, of whom I was one, examined whether avoiding insulin resistance, which is associated with aging, might lengthen life span in rodents as indicated by previous studies using caloric-restricted animals. We assessed whether consuming niacin-bound chromium (NBC) alone or in a formula containing other so-called "insulin sensitizers" would overcome various manifestations of aging and extend life span in Zucker Fatty Rats (ZFR).⁷ As we report in the abstract of our research, we "compared many metabolic parameters of ZFR fed NBC alone (n=12) or NBC in a unique formula (n=10) to a control group (n=10). In addition to NBC, the formula contained Allium sativum, Momordica charantia, Trigonella foenum-graecum and Gymnema sylvestre. The formula group received roughly ½ as much NBC daily as the NBC group. At week 44, all rats still lived, and no abnormalities in blood count (CBC), renal, or liver functions were found. In the two treatment groups compared to control, circulating glucose levels were significantly lower, with a trend toward lower HbA1C. Relatively elevated cholesterol and triglyceride concentrations occurred in the formula group. Compared to control, the NBC group had increased average lifespan (21.8%), median lifespan (14.1%), 30th percentile survival (19.6%), and maximum lifespan (22%). Despite similar beneficial effects on the glucose and blood pressure systems, a difference in aging was also found when the NBC group was compared to the formula group. When all rats in the other two groups had died, four in the NBC group continued to live at least a month longer."

The fact that the life extension benefits of supplementation with chromium were undone by the inclusion of the other ingredients despite similar improvements in markers, such as blood glucose and blood pressure, was the source of considerable discussion in our group. My position at the time was and remains that the "insulin sensitizer" approach is beneficial. However, one of the ingredients in the formula, Gymnema sylvestre, is not an insulin sensitizer; instead, it is an inducer of insulin release from the pancreas, thus can elevate insulin levels or prevent a lowering of such levels even in conjunction with better insulin sensitivity. Elevated levels of circulating insulin are damaging the arteries and to many systems of the body regardless of any apparent benefit in terms of lowering circulating glucose and HbA1C. Adding this inappropriate ingredient to the mix negated benefits in terms of actual final endpoints, in this case extended lifespan, as opposed to improving mere markers.

Conclusion
The American diet notoriously tends to be restricted in terms of the range and types of foods included. Surprisingly small changes in the diet that increase the variety of polyphenols and other nutrients, mostly plant-derived, can lead to quite outsized effects in terms of benefits. As described above in one example, plant nutrients equal to a small portion of a well-designed curry plus a cup of green tea yielded significant returns in terms of prostate health. Dietary supplements can be useful aids to enlarging the range of nutrients consumed each day, but supplements do not take the place of fresh food properly prepared and eaten in variety. Moreover, supplement interactions are not always obvious and need to be observed carefully.

Endnotes

1. van Die MD, Williams SG, Emery J, Bone KM, Taylor JM, Lusk E, Pirotta MV. A Placebo-Controlled Double-Blinded Randomized Pilot Study of Combination Phytotherapy in Biochemically Recurrent Prostate Cancer. Prostate. 2017 May;77(7):765 –75.
2. Gliemann L, Schmidt JF, Olesen J, Biensø RS, Peronard SL, Grandjean SU, Mortensen SP, Nyberg M, Bangsbo J, Pilegaard H, Hellsten Y. Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men. J Physiol. 2013 Oct 15;591(20):5047–59.
3. Gliemann L, Nyberg M, Hellsten Y. Effects of exercise training and resveratrol on vascular health in aging. Free Radic Biol Med. 2016 Sep;98:165–76.
4. Alway SE, McCrory JL, Kearcher K, Vickers A, Frear B, Gilleland DL, Bonner DE, Thomas JM, Donley DA, Lively MW, Mohamed JS. Resveratrol Enhances Exercise-Induced Cellular and Functional Adaptations of Skeletal Muscle in Older Men and Women. J Gerontol A Biol Sci Med Sci. 2017 Nov 9;72(12):1595 –1606.
5. Pollack RM, Barzilai N, Anghel V, Kulkarni AS, Golden A, O’Broin P, Sinclair DA, Bonkowski MS, Coleville AJ, Powell D, Kim S, Moaddel R, Stein D, Zhang K, Hawkins M, Crandall JP. Resveratrol Improves Vascular Function and Mitochondrial Number but Not Glucose Metabolism in Older Adults. J Gerontol A Biol Sci Med Sci. 2017 Nov 9;72(12):1703 – 09.
6. Simioni C, Zauli G, Martelli AM, Vitale M, Sacchetti G, Gonelli A, Neri LM. Oxidative stress: role of physical exercise and antioxidant nutraceuticals in adulthood and aging. Oncotarget. 2018 Mar 30;9(24):17181– 98.
7. Preuss HG, Echard B, Clouatre D, Bagchi D, Perricone NV. Niacin-bound chromium increases life span in Zucker Fatty Rats. J Inorg Biochem. 2011 Oct;105(10):1344 – 9.

lycopene prostate macronutrients resveratrol vascular health