Sign-Up for the Life Health Performance Newsletter

Payment Processing

102 Studies Can't Be Wrong!

When it comes to your health, you probably believe in doing your homework.  Medical literature and nutritional science journals are filled with studies that demonstrate the sound science behind whole food concentrates.  We've given you a jumpstart on your homework by sorting through all the information that's out there. On this page, you'll find citations to the leading nutritional research that guides each and every one of BerryBoost's formulas.

Section 1: General Health Issues

Section 2: Chokeberry

Section 3: Elderberry

Section 4: Black Currant



Section 1: General Health Issues

Benefits of fruits and vegetables and whole food concentrates

1. Stich, E., Kloos, K. (2000) Fruit and vegetable extracts rich in dietary phytochemicals. Food Industry Journal. Issue 3.
Summary: For years a diet rich in fresh fruits and vegetables has been promoted for optimal health. The basis of this recommendation has been their vitamin content. There is now growing evidence that the PRIMARY benefit of fruits and vegetables is the secondary plant substances or dietary phytochemicals (DPCs). Dietary phytochemicals are micronutrients designed to help the plants fight off disease, pests, and sun damage. DPCs are estimated to be in the range of 10,000 to 30,000 in various plants. These exist in very small amounts and cannot be found in vitamin supplements - even those that contain isolates such as lutein and lycopene. Moreover, unlike many vitamins, DPCs cannot be produced by the human system. Scientific evidence demonstrating the role of DPCs in health and disease prevention is growing rapidly. Science now believe that DPCs play a vital role in the prevention of cancer, heart disease, strengthening the immune system, and possess anti-viral and anti-inflammatory effects and may help to reduce cholesterol and blood pressure.  For individuals who are not able to obtain the full range of fruits and vegetables in high enough quantities, whole food concentrates offer a perfect way to eat healthy. The article highlights elderberry and chokeberry as possessing the highest levels of anthocyanins, one of the most important DPCs found. This article also highlights the importance of proper harvesting and processing to preserve the DPC content. Functional food concentrates are likely to contain higher levels of DPCs due to the fact they are harvested and processed in ways to preserve their nutrient content. On the other hand, many fresh fruits and vegetables lose a great deal of their DPC content due to the long process of storage before and after arriving at the store. The time of year that functional whole food concentrates are harvested is also important in maximizing DPC content. Another benefit of functional whole food concentrates is that undesirable components such as sugars and acids are reduced. The result is finished products with standardized DPC content.

2. Dubois, R. Oxidative stress in the pathogenesis of disease and aging; opportunity for intervention. Center for Treatment of Infectious Diseases. Atlanta, Georgia.
“Normal metabolism produces free radical molecules. Oxidative stress is the imbalance between free radical production and the antioxidant cascade. This stress is associated with the pathogenesis of multiple disorders including cancer, stroke, coronary heart disease, cataracts, macular degeneration, depression, and even the rate of aging. ..There are thousand of phytochemicals that are not designated as vitamins that have an important role in human nutrition. As antioxidants, phytochemicals are destroyed and must be replenished or reconstituted continuously. That is, we must eat them every day. Only 9% of Americans eat five servings of vegetables and four servings of fruit each day. Cooking can destroy up to 98% of the free folic acid in foods. Aging is nutrition and oxidative stress dependent. Free radical damage increases with age and is less well contained and repaired by aged cells. Vitamins A, C, and E did not prevent Age Related Macular Degeneration. Consumption of green leafy vegetables was associated with 43% less cataracts and a serving of green leafy vegetables on a daily basis was associated with 86% less risk of AMD. Lutien/zeaxanthin is the antioxidant associated with protection of the macula. Multiple studies have shown exercise, particularly distance running, produces oxidative stress and cumulative damage with increased risk of infection. The pathogenesis of Alzheimer's disease may involve oxidative stress and the accumulation of free radicals. Isolated supplements have shown paradoxical, conflicting and even harmful results in careful studies. This is the result of efforts to use single components of the antioxidant cascade without taking into account the balance and interdependence of the system. Whole foods are the best source of micronutrients; they have thousands of as yet unidentified phytochemicals of presumed benefit for human nutrition. Bioavailability of micronutrients from powdered fresh fruits, vegetables and grains in some situations may actually be better than from standard food sources. Bioavailability, safety, and efficacy of powdered fruits, vegetable and grains has been demonstrated.”

3. Wise, J., Morin, R., Sanderson, R., and Blum, K. (1996). Changes in Plasma carotenoid, alpha-tocopherol, and lipid peroxide levels in response to supplementation with concentrated fruit and vegetable extracts: a pilot study. Current Therapeutic Research. 57(6): June.
Summary: “Free radical damage to cell membranes, DNA, and other vital cell constituents may contribute to cardiovascular disease, cancer, and other degenerative diseases. Epidemiological evidence has equated high dietary (versus vitamin isolates) intake of vitamins E and C and carotonoids with a reduced risk of coronary heart disease, cancer, stroke and cataracts. Studies in which blood levels of these same compounds were measured showed that as blood levels of these antioxidants increase, the risk of disease decreases. Furthermore, sub optimal levels of each factor increase the risk singly, whereas combined deficits of antioxidants increase risk by a multiple factor. In recent intervention trials for the prevention of cancer or CHD, large oral doses of beta-carotene (isolate) have not been shown to have any effect on the outcome of either disease; other studies have shown beta-carotene to have adverse effects on cancer and CHD in smokers…These conflicting and disappointing studies failed to sufficiently consider the potential interactions of these bio protective nutrients, and the effects of high doses of a single nutrient on absorption, transport, recycling, and tissue specificity of other dietary constituents. ...We enrolled 15 healthy subjects with no history of gastrointestinal surgery, diabetes mellitus, or other serious pathogenetic condition.” Participants were given fruit and vegetable extracts. Diets were not altered. After supplementation, plasma beta-carotene levels increased approximately sixfold, but represented only 10.4% of plasma carotenoids, whereas alpha-carotene, lutein, zeaxanthin, and especially lycopene levels increases significantly. Overall, the increases in plasma carotenoids in response to supplementation with fruit and vegetable powders appears to be substantially greater than with similar quantities of carotenoids in food. Given the modest levels of beta-carotene and even lowers levels of other carotenoids supplemented daily, it appears that they are much more readily absorbed than are the same micronutrients in foods.”

4. Smith, M., Inserra, P., Watson, R., Wise, J., and O’Neill, K. (1999). Supplementation with fruit and vegetable extracts may decrease DNA damage in the peripheral lymphocytes of an elderly population. Nutrition Research. 19(10): 1507-1518.
Summary: “We tested the concept that a daily regimen of supplementation with fruit and vegetable extracts would reduce DNA damage in the peripheral lymphocytes in the elderly. In a blind study, a group of twenty elderly volunteers mean age 68 were given supplements twice daily for 80 days with blood samples drawn before and after intervention. In this initial study, we conclude that a daily course of fruit and vegetable extract supplementation may reduce the level of DNA damage found in the peripheral lymphocytes of seniors. … Oxidative damage to cells has been proposed as a mechanism for the aging process. … Oxidative insults to DNA can lead to mutations in crucial genes, which ultimately may lead to cancer. Potent antioxidants and nutrients from fruits and vegetables may be able to quell the effects of oxidative DNA damage in the aged, in addition to lowering rates of heart disease and the overall risk for cancer.

5. Kaats, G., Wise, J., Morin, R., Pullin, D., Squires, W., and Hesslink, R. (1997). Positive effects of nutritional supplements on body composition biomarkers of aging during a weight loss program. Study presented in part at the 5th International conference on Anti-aging Medicine and Bio Medical Technology, Las Vegas, NV: December 13-15, 1997.
Summary: “Since oxidative stress is known to increase during caloric restriction, enhanced antioxidant protection would be expected to be beneficial. The weakening of the body caused by a change in body composition in favor of fat and at the expense of muscle, “sarcopenia”, is an important biomarker of aging. This gradual loss of muscle mass can be slowed or reversed by interventions including exercise and dietary changes. Weight loss diets focus only on scale weight and result in significant losses in lean muscle mass, thus accelerating the aging process. In this study body composition changes were used to evaluate the success of a weight loss program using nutraceutical-based dietary supplements. An experimental and control group, each containing 50 subjects, were assessed for baseline body composition using Lunar Dual Energy X-ray Absorptiometry scanning technology. During the 60-day test period, both groups followed the same behavior modification program and dietary plan with modest calorie restrictions. In addition, the experimental group consumer nutraceutical-containing nutritional supplements designed to support lean muscle and reduce body fat, while the control group consumed placebo. Post study tests showed that both groups lost scale weight, but the difference was not significant. However, the experimental group had a greater reduction in body fat (-2.4% vs. -.8%) lost 2.5 times more body fat and gained more fat free mass and achieved a threefold greater improvement in overall body composition. The results provide compelling evidence for the efficacy of these dietary supplements to improve body composition by reversing sarcopenia through the depletion of excess body fat while simultaneously increasing lean muscle mass. This suggests that well-designed nutritional supplements should be considered as a necessary component of programs designed to deplete excess body fat while preserving or enhancing lean muscle mass.”

6. Panagiotakos, D., Pitsavos, C. et al. (2003). Consumption of fruits and vegetables in relation to the risk of developing acute coronary syndromes; the Cardio 2000 case-control study. Nutrition Journal. 2(1): 2
Summary: consumption of fruits and vegetables seems to offer significant protection against Coronary Heart Disease. The higher the intake of fruits and vegetables, the lower the risk. Compounds such as flavonoids, phytakes, lycopene, carotonoids, and other phytochemicals in fruits and vegetables may have a significant protective effect in reducing CHD.

7. Hagfors, L., Leanderson, P., et al. (2003)Antioxidant intake. Plasma antioxidants and oxidative stress in a randomized, controlled, parallel, Mediterranean dietary prevention study on patients with rheumatoid arthritis. Journal of Nutrition. 2(1): 5
Summary: patients with rheumatoid arthritis that adopted a Cretan Mediterranean diet obtained a reduction in inflammatory activity, and increase in physical function and in vitality. There is evidence that low anti oxidant status is associated with a higher risk of developing RA. Furthermore, the rheumatoid inflammation is associated with an increased generation of free radicals. Most controlled studies investigating the therapeutic effect of antioxidant vitamin isolates have not shown any significant effects on RA symptoms. Since many antioxidant compounds interact in the body, supplementation with individual antioxidants may not be the best way to strengthen antioxidant defense.

8. Cristofalo, V., Adelman, AR., and Schaie, K. (2002). Annual Review of gerontology and geriatrics: focus on modern topics in the biology of aging. New York: Springer Publishing. “There is a long history of evidence showing a significant association between fruit and vegetable intake and decreased mortality from cardiovascular disease. Therefore, it may be that increasing the intake of dietary antioxidants may have protective effects on CNS function similar to those seen with respect to cancer and cardiovascular disease. Subsequent research showed that fruit and vegetable extracts containing high levels of anthocyanins and other flavonoids also exhibited increased levels of total antioxidant activity as assessed via the ORAC assay.“ pp. 206-207

9. Haber, D. (2003). Health Promotion and Aging. New York: Springer Publishing
Summary: Nutritional intake declines with age. Absorption of important nutrients decreases with age. Problems with vitamin isolates. “There are good reasons to be more cautious taking dietary supplements than the general public appears to be. Most dietary supplements are narrowly targeted while the nutrients in foods work in synergy. Phytochemicals are an example of this distinction. There are recently discovered chemical compounds found in abundance in fruits and vegetables, which seem to exert powerful synergistic effect in cancer prevention. These compounds are presently impossible to replicate in pill form. In addition, people on medication need to be careful with taking dietary supplements. For instance someone taking coumadin, a blood thinning medication, should avoid vitamin K and also avoid several herbs like gingko biloba. Antioxidants are found primarily in fruits and vegetables. Few Americans get adequate servings of fruits and vegetables."

10. Victoroff, J. (2002). Saving your brain. New York: Bantam Books.
Summary: “few studies confirm that vitamins by themselves do the trick (supplying enough antioxidants). If vitamins can’t fully explain the benefits of plant-rich diets, then something else must be going on. That something else is probably phytochemicals. … Evidence is growing that a fruit and vegetable rich diet does even more. By keeping brain vessels open, blocking free radical attacks, protecting DNA, and reducing inflammation, such a diet directly opposes many of the demonic forces that underlie Alzheimer’s itself…I can’t put this strongly enough: though much more research is needed and the size of the benefit may not be determined for years to come, a fresh fruit and vegetable rich diet is a sensible and remarkably safe bet to keep your brain in top working order.” Most dementia including Alzheimer’s as well as cardiovascular disease can be traced to free radical damage. “ Can antioxidants (from fruits and vegetables) prevent stroke, protect or even enhance human cognition, and help save the brain from Alzheimer’s? The answers are probably yes, yes, yes.” On the other hand, antioxidant isolates such as vitamin C and E can actually undercut the benefits of cholesterol lowering drugs. “I favor the whole foods approach, because the blueberry may contain a dozen antioxidants, so its better to eat the whole blueberry rather than a pill containing just one antioxidant.“ pp. 210-245.

11. Inserra, P., Shuguang, J., Solkoff, D., Lee, J., et al (1999). Immune Function in elderly smokers and nonsmokers improves during supplementation with fruit and vegetable extracts. Integrative Medicine. 2(1): 3-10.
Summary: “Epidemiological evidence suggests fruits and vegetables reduce risk of cardiovascular disease and cancer. Immune function declines with age as CVD and cancer incidence rises and may be related to poor antioxidant status. The study investigated how fruit and vegetable extracts containing multiple antioxidants and phytonutrients affect immune function in the elderly. 53 subjects with mean age of 68 consumed extracts for 80 days. Blood samples were taken at baseline, 40, and 80 days. Significant increases were found in serum antioxidants when baseline values were compared at 80 days. Spontaneous proliferation of PBM cells increased significantly. Natural killer cells (NK) cell cytoatoxicity significantly increased at effector to target cell ratios of 100:1. Supernatatn from PBM cells stimulated with phytohemaglutinin resulted in significant two fold increases in interleuken-2. Additionally, statistically significant increases in IL-2 production were seen in smokers. Fruit and vegetable extract supplementation significantly enhanced multiple measures of immune function in elderly subjects, and improved IL-2 levels in smokers. Fruit and vegetable extract supplementation offers a novel way to improve compliance with current nutritional recommendations and may potentially lower disease risk…Fruits and vegetable extracts are a safe and well-tolerated supplement to dietary fruits and vegetables.”

12. Can Foods Forestall aging? (1999) Agricultural Research. February.
Summary: “ Studies at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University suggest that consuming fruits and vegetables with a high ORAC value may help slow the aging process in both body and brain. …Foods contain more than 4,000 flavonoids. These constitute a major class of dietary antioxidants and appear to be responsible for a large part of the protective power of fruits and vegetables. … Food antioxidants not only are absorbed, they boost the antioxidant power of the blood. “Increasing the level of fruits and vegetables increases the ORAC absorbed evidenced by increases in blood antioxidant levels. The increase in plasma ORAC can’t be fully explained by the increases in plasma levels of vitamin C, vitamin E, or carotenoids, so the body must be absorbing other components in these fruits and vegetables. The antioxidant capacity of the blood seems to be tightly regulated. Still a significant increase of 15 to 20 percent is possible by increasing consumption of fruits and vegetables, particularly those high in antioxidant capacity. The ORAC values of fruits and vegetables cover such a broad range, you can pick seven with low values and get only about 1,300 ORAC units, or you can eat seven with high values and reach 6,000 ORAC units or more. ORAC consumption intake should be increased to between 3,000 and 5,000 ORAC units to have a significant impact on plasma and tissue antioxidant capacity.

13. Knekt, P., Kumpulainen, J., vinen, R., et al. (2002). Flavonoid intake and risk of chronic diseases. American Journal of Clinical Nutrition. Spet76(3):560-8. The association between flavonoid intake and risk of several chronic diseases was studied. Persons with higher quercetin intakes had lower overall mortality from ischemic heart disease. Men with higher quercetin intake had a lower lung cancer incidence and men with higher myricetin intakes had a lower prostate cancer risk. A trend toward a reduction in risk of type 2 diabetes was associated with higher quercetin and myricetin intakes.

14. Manson, J., Shari, S., Bassuk, D. et al. (2003). Does vitamin E supplementation prevent cardio vascular events? Journal of Women’s Health. 12(2):123-136. Summary: “At this time there is insufficient evidence for making a public health recommendation to use vitamin E supplements to prevent cardiovascular disease. In contrast, increased intake of antioxidant rich fruits and vegetables should be promoted as an important part of a healthy diet because such foods provide a range of nutritional benefits beyond any potential effects of antioxidant(supplements).”

15. John, J., Ziebland, s., Yudkin, P., et al. (2002). Effects of fruit and vegetable consumption on plasma antioxidant concentrations and blood pressure: a randomized controlled trial. The Lancet. June 8: 359(9322): 1969-1974. The study evaluated the effects of an intervention to increase fruit and vegetable consumption on plasma concentrations of antioxidant vitamins, blood pressure, and daily fruit and vegetable intake. The authors concluded that fruit and vegetable interventions over the short term have beneficial effects on risk factors for CVD. Increasing fruit and vegetable intake has a positive effect on blood pressure and would lead to reductions in heart disease.

Berries and disease prevention, including diseases of the brain such as Alzheimer's

1. Joseph, J., Shukitt-Hale, B., Dnisova, N., (1999). Reversals of Age-related declines in neuronal signal transduction, cognitive , and motor behavorial deficits with blueberry, spinach, or strawberry supplementation. The Journal of Neuroscience, September 19(18):8114-8121.
Summary: ample research supports the belief that oxidative stress creates age-related neuronal-behavior decrements that may be mitigated with anti oxidants. This study showed that functional whole food concentrates blueberry, strawberry, and spinach in dose dependent amounts backed up previous research in showing how effective these substances were in reversing age-related deficits in several neuronal and behavioral parameters. The study suggests that in addition to their known beneficial effects on cancer and heart disease, phytochemicals present in anti oxidant rich foods may be beneficial in reversing the course of neuronal and behavioral aging. (Chokeberry and elderberry are both higher in antioxidant power and anthocyanin content than blueberry, strawberry, or spinach(see ORAC chart)

2. Cristofalo, V., Adelman, AR., and Schaie, K.(Eds) (2002). Chapter 9. Neuronal environment and age-related neurodegenerative disease: nutritional modification. Joseph, J., Denisovea, N., Youdim, K., Bielinski, D. et al. Annual Review of gerontology and geriatrics: focus on modern topics in the biology of aging. New York: Springer Publishing. “Blueberry concentrate was effective in reversing age-related deficits in several neuronal and behavioral parameters”. P. 207. “We have shown for example that the anthocyanins and hydroxycinnamates in blueberry have very potent antioxidant properties and anti-inflammatory properties (against tumor necrosis factor, TNFalpha) in vascular endothelial cells, and blueberry extract is effective against TNFalpha-induced decrements in calcium buffering in M1AchR-transfected COS7 cells” 208-209. (Chokeberry and elderberry are higher in ORAC and anthocyanin content than blueberry.)

Anthocyanins: benefits, safety, absorbability

Hou, D. (2003). Potential mechanisms of cancer chemoprevention by anthocyanins; Current Molecular Medicine. 3:149-159
Epidemiological studies support the thesis that ingestion of fruits and vegetables containing anthocyanins lower the risk of cardio vascular disease and improvement of visual function. This article summarized the most recent findings regarding anthocyanins and cancer chemoprevention.
“Anthocycanins can be directly absorbed and distributed in the blood.”
Potential effects of anthocyanins on health:
1. Antioxidation: anthocyanins are powerful anti and can re-establish plasma antioxidant capacity and decrease vitamin E deficiency in cases of low vitamin E intake.
2. Anticarcinogenesis: Anthocyanins, particularly cyanidin (present at high levels in elderberry and chokeberry) showed reduced lesion development in colons of rats as well as other anti-tumoric activities.
3. “Apoptosis plays an important role in elimination of seriously damaged cells or tumor cells by chemo preventative agents.” Anthocyanins, particularly cyanidin (present at high levels in chokeberry and elderberry) induced apoptosis.
4. Anti-mutagenicity: “Cyanadin showed stronger activity of anti-mutagenicity than peonidin. Based on additional studies with enzyme activity, the authors concluded that anthocyanins protected against the mutagenesis.”
5. Anti-inflammatory activity: “cyanidin showed better anti-inflammatory activity than aspirin” The anti inflammatory activity of cyanadin was comparable to that of naproxen, which is a non-steroidal anti-inflammatory drug.”
6. Anthocyanins may reduce the oxidative stress of nitric oxide and increase the protective effects against cardiovascular and chronic inflammatory disease.
7. Potent inhibitor of the epidermal growth-factor receptor (EGFR). ”EGFR is one of cell-surface proteins conveying growth stimulatory signals across the cell membrane. EGFR is involved in the aberrant growth of many types of human cancer cells. Meiers et al found that cyanidin and delphinidin (contained in black currant) inhibited the tyrosine kinase activity of EFGR and suggest that cyanidin and delphinidin may be potent inhibitors of EGFR.”
8. Potent inhibition of tumor cell invasiveness. Metastasis is the major cause of cancer mortality. Delphinidin (contained in black currant) may inhibit tumor cell invasiveness.
9. Estrogenic activity. Test results “suggest that anthocyanins exert estrogen activity, which might play a role in altering the development of hormone-dependent adverse effects.”
10. Bioavailability. Most results indicated that anthocyanins were directly absorbed and bioavailable to humans. Anthocyanins can be absorbed within two hours of ingestion. Other tests show plasma antioxidant capacity was significantly elevated within thirty minutes. Another test showed that anthocyanins are absorbed in their unchanged glycated forms in elderly women.
11. Tolerability and Safety. “A highly purified extract from V. myrtillus berries containing 36% anthocyanins has been used to test the tolerability and safety of anthocyanins in animals.” Extremely high doses given over six months to mice and rats and dogs did not cause death or any toxic effects and did not affect fertility in rats. The extract did not show any teratogenic effect and mutagenic activity. “The clinical safety was confirmed in a post marketing surveillance study. Most persons took 160 mg twice daily for six months. In most cases, the extract was well or very well tolerated. Only 4% of persons complained of side effects, mainly gastrointestinal or concerning skin and cutaneous annexes, and nervous system.”

Conclusion: tests support the antioxidant, anti-mutagenicity, anti-inflammatory, anti-carcinogenis and apoptosis induction of malignant cells, in cancer chemo prevention. The studies generally relied on very high doses supporting the idea that results are dose dependent.

Bioavailability of elderberry and chokeberry anthocyanins versus other flavonoids

Walle, T. (2004. Serial Review: flavaonoids and isolfalvones(Pytoestrogens): Absorption, Metabolism, and bioactivity. Free Radical Biology and Medicine 36(7) pp. 829-837

This article reviews the bioavailability of various flavonoids. "Dietary flavonoids, a class of semi-essential food components, have long been believed to exert protective effects against many diseases, in particular cardiovascular disease and cancer …The anthocyanin branch of the flavonoid family has numerous members, which are found mainly in berries and have biological properties suitable for disease prevention. They exist in the diet mainly as glucosides with cyanidin3-glucoside as the prototype (elderberry). The key difference compared with other flavonoid glucosides, however, is that they appear to be absorbed after oral ingestion…The consistency of findings of oral absorption of these flavonoid conjugates, compared with flavonoids in general, warrants special attention. … Anthocyanins are positively charged oxonium compounds compared with the other, largely neutral, flavonoids. One could speculate that the positively charged anthocyanins may be affected by MRP2 efflux, which seriously limits absorption of other flavonoid glycosides …The limiting factors for tea flavonoids in humans appear to be a combination of poor transport across the enterocyte and very efficient metabolism of the compounds by conjugation."

Free radicals and diseases often associated with aging including Alzheimer's Disease, cardiovascular diseases including stroke and heart attack, osteoporosis, macular degeneration, cancer, cognitive decline, diabetes, osteo and rheumatoid arthritis

1. Short, R. Williams, D., and Bowden, D. (1997) Circulating antioxidants as determinants of the rate of biological aging in pigtailed macaques. The Journals of Gerontology: Biological Sciences and Medical Sciences 52(1): B26-B38.
The effect of anti oxidant activity on the rate of biological aging was studied in 39 pigtailed macaques 7-30 years of age. The rate of biological aging was formed from seven physiological variables that met a stringent set of criteria as biomarkers of aging. The study results further validated the rate of biological aging variable as a measure of the rate of biological aging and supported the concept that anti oxidant activity influences both the rate of biological aging and vulnerability to disease.

2. Chatgilialoglu, C., and O’Neill, P. (2001). Free radicals associated with DNA damage. Experimental Gerontology September; 36 (9):1459-71 This short review focuses on the chemical events related to DNA damage induced by free radicals.

3. Komosinska, K., Olczyk, K. (199%). The role of free radicals in pathogenesis of insulin dependent diabetes mellitus. Postepy Hig Med Dosw. 49(6);733-46.
Summary: explains the role of free radicals in the development of diabetes mellitus.

4. Mori, A., Liu, J., Want, X., Kawai, M. Free radical scavenging by brain omogenate: implication to free radical damage and anti oxidant defense in brain. Neurochem Int. March;24(3):201-7.
Summary: confirmed role of free radicals and brain damage and the role of anti oxidants from food in mitigating brain damage.

5. Hajizadeh, S., DeGroot, J., TeKoppele, J., Tarkowski, A., Collins, L. (2003) Extracellular mitochondrial DNA and oxidatively damaged DNA in synovial fluid of patients with rheumatoid arthritis. Arthritis Therapy. 5(5):234-240
Summary: discusses the role of oxidative stress from free radicals in the inflammatory process and relationship to RA.

6. Alagiakrishran, K., Juby, A., hanley, D., Tymchak, W., Sclater, A. (2003). Role of vascular factors in osteoporosis. Journal of Gerontology: Medical Sciences 58(4):362-366.
Summary: discusses the role of vascular health and disease in the prevalence of osteoporosis due to the role of the blood supply to the bone. A diminished supply of blood appears to increase the risk for osteoporosis. Endothelial dysfunction plays a role because it is an early marker for vascular disease. In animal studies, the inhibition of NO production was marked by significant bone loss.

7. University of California, Irvine College of Medicine. (2000). Link found between excess free radicals and high blood pressure. Medscape Medical News.
Summary: a team of researchers at UCI College of Medicine found that high blood pressure and can be increased and then reduced by changing the levels of highly reactive oxygen molecules called free radicals and nitric oxide, which is currently being studied for its role in cardiovascular disease and other functions in the body. The researches found a link between low levels of nitric oxide and high blood pressure. “This study showed that although hypertension is a highly complex disorder that can arise from a number of causes, nitric oxide and oxidative stress play a major role in regulating blood pressure. We think this study provides the first insight into the interaction between oxidative stress and nitric oxide … Antioxidants are powerful regulators of blood pressure, and our studies show that multiple types of these chemicals, found in a diet heavy in fruits and vegetables, could help mitigate blood pressure.”

8. Schoonover, L. (2001). Oxidative stress and the role of antioxidants in cardiovascular risk reduction. Progressive Cardiovascular Nurse. 16(1):30-32.
Summary: The contribution of free radicals and vascular damage is well accepted. The impact of dietary supplementation and treatment with antioxidant vitamin isolates remains controversial. The injury caused by oxidative stress can affect all organ systems. Oxidation of LDL cholesterol is a key factor in the development of atherosclerosis. Free radicals appear to be involved throughout this process. Reports of clinical studies of antioxidant vitamin isolate supplementation have documented controversial and contradictory outcomes. Due to the lack of conclusive data in the setting of primary prevention of cardiovascular events and the potential detrimental effects of vitamin isolates, The American Heart Association recommends consumption of antioxidant rich foods as opposed to vitamin supplementation.

9. McDermott, J. (2000). Antioxidant nutrients: current dietary recommendations and research update. Journal of American Pharmacological Association. 40(6):785-799.
Summary: a meta analysis of research on antioxidants. “Overall it appears that antioxidant nutrients, especially in food sources, have an important role in preventing pathogenic processes related to cancer, heart disease, macular degeneration, cataracts, and may enhance immune function. Isolation of specific antioxidant nutrients may not confer the same health benefits as do whole foods. The greatest benefits of antioxidant nutrients are seen in epidemiological surveys in which antioxidant nutrients are primarily derived from dietary sources, particularly fruits and vegetables.”

10. Laties, A., (1999). Search for Medical therapy: Focus on oxidative stress. Digest Journal of Ophthalmology. 5(1).
Summary: discusses link between free radicals and diseases of the eye. Suggests that high intakes of fruits and vegetables may inhibit occurrence of eye diseases. Focus on role of lutein and zeaxanthin in prevention.

11. Schmeichel, A., Schmelzer, J., Low, P. (2003). Oxidative Injury and apoptosis of dorsal root ganglion neurons in chronic experimental diabetic neuropathy. Diabetes. 52(1):165-171.
Summary: oxidative stress increases with diabetes. Oxidative stress is associated with a number of diseases including heart disease possibly explaining the role of diabetes and heart disease increases.

12. Hadjigogos, K. (2003). The role of free radicals in the pathogenesis of rheumatoid arthritis. Panmiverva Medicine. March;45(1):7-13
Summary: There is mounting evidence that free radicals contribute to various disease entities including inflammatory joint disease. This reaction may be self-perpetuating within the rheumatoid joint, suggesting free radicals play a role in the chronicity of the inflammatory reaction which is a key question regarding to which extent free radicals contribute to the consequences of inflammation, such as the cartilage and bone destruction. (ISSN:0031-0808)

Exercise and Stress, Muscle Damage, and Immune Function

1. Supinski, G. (1998)Free Radical induced respiratory muscle dysfunction. Molecular Cell Biochemistry. Feb;179(1-2):99-110.
Summary: A series of studies discovered that free radicals generated during strenuous exercise may modulate respiratory muscle contraction and contribute to the development of muscle fatigue. The data supporting this concept include: (a) studies that evidence heightened free radical production in contracting muscle, (b) evidence that pharmacologic depletion of muscle antioxidant stores increases muscle fatigue present after a period of exercise and (c) evidence that the administration of agents that act as free radical scavengers retard development of muscle fatigue.

2. Buck, C.(2003) Harvest of Champions. Outside, March.
“Chief among the protective substances (from fruits and vegetables) are phytochemicals, powerful antioxidants that counteract the cellular damage all exercise inflicts. It’s oxidative damage – breaking down of muscle tissue by vicious atom clusters called free radicals – that make you sore.”

3. Hoffman, J., Maresh, C., Newton, R., Rubin, M. et al. (2002). Performance, biochemical, and endocrine changes during a competitive football game. Medical Science Sports Exercise. Nov. 34(11):1845-53.
This study represents the first time that anaerobic power performance was examined during an actual intercollegiate American football game. Biochemical and endocrine responses also were examined to access the physiological stress imposed by this competitive contest. Cortisol concentrations were significantly higher for ST and IP than RS. Conclusions: performance, biochemical, and endocrine changes in these NCAA Division III football players reflected the stress and muscle damage that occurs as a result of a competitive American football game.

4. Venkatraman, J., and Pendergast, D. (2002). Effect of dietary intake on immune function in athletes. Sports Medicine. 32(5):323-37.
Athletes are exposed to acute and chronic stress that may lead to suppression of the immune system and increased oxidative species (free radical) generation. In addition, the tendency to consume fewer calories that expensed and to avoid fats may further compromise the immune system and anti oxidant mechanisms. The exercise stress is proportional to the intensity and duration of the exercise. Muscle glycogen depletion compromises exercise performance and it also increases stress. Many athletes do not take in enough nutrients to support exercise performance, immune competence and antioxidant defenses. Either overtraining or under-nutrition may lead to an increased risk of infections. Exercise stress leads to a proportional increase in stress hormone levels and concomitant changes in several aspects of immunity, including the following: high cortisol; neutrophilia; lympopenia; decreases in granulocyte oxidative burst, nasal mucociliary clearance, natural killer cell activity, lymphocyte proliferation, the delayed-type sensitivity response, the production of cytokines in response to mitogens, nasal and salivary immunoglobulin A levels; blunted major histocompatibility complex II expression in macrophages; and increases in blood granulocyte and monocyte phagocytosis, and pro-and anti-inflammatory cytokines. In summary, athletes should eat adequate calories and nutrients.

5.  Dressendorfer, R., Peteresen, S., Moss, L., Hannon, j., et al.(2002) Performance enhancement with maintenance of resting immune status after intensified cycle training. Clinical Journal of Sports Medicine. Sept, 12(5):301-7.
Unaccustomed intense endurance exercise is associated with short-term suppression of natural immunity.

6.  Fitzgerald, M. (2002). Drink to your health. Fitness Runner: Sept. Oct. pp. 20-22.
25 to 50% of runners suffer overuse injury that prevents them from a period of time. Other research indicates that runners in intense training modes are more likely to contract an upper respiratory infection than inactive individuals. Well-formulated sports drinks can help prevent these injuries and illnesses. With proper ingredients, these drinks can help prevent and even repair injured tissue and bolster the immune system.
During heavy workouts, the immune system is suppressed. This suppression can last up to 72 hours. Cortisol is the primary cause of this problem.
Oxidative stress caused by free radicals increases dramatically during exercise. Cortisol is released when glycogen runs low and the body is required to break down more protein for energy. “Cortisol does the breaking and destroys muscle protein in the process. Sports drinks can delay and reduce this action in the same way they protect the immune system: by conserving muscle glycogen and by stimulating insulin release.”

7. Pedersen, B., Rohde, T., Ostrowski, K. (1998) Recovery of the immune system after exercise. Acta Physiology Scandanavia. March; 162(3):325-32.
In the recovery phase after intense exercise is found suppressed blood concentrations of lymphocytes, suppressed natural immunity of blood lymphocytes, decreased concentrations of secretory IgA in mucosa, but increased blood concentration of neutrophils and increased levels in the blood of inflammatory cytokines. Thus, after intense long-term exercise, the immune system is characterized by concomitant inflammation and temporary suppression of the cellular immune system, the most pronounced findings being 2-4 hours after exercise. The underlying mechanisms are multifactorial and include neuroendocrinological and metabolic factors. High levels of cytokines, especially interleukin-6, are found in the recovery period after eccentric exercise, and it has been demonstrated that a close association exists between muscle damage and increased levels of interleukin-6.

8.  Stupa, N., Lowther, S., Chorneyko, K., bourgeois, J., Hogben, C., Tarnopolosky, M. (2000). Gender differences in muscle inflammation after eccentric exercise. Journal of Applied Physiology. Dec;89(6):2325-32.
Unaccustomed exercise is followed by delayed onset muscle soreness and morpholocal changes in skeletal muscle. The researchers studied the effect of eccentric exercise in untrained male and female subjects. The study concluded that muscle damage is similar between genders, yet the inflammatory response is attenuated in women versus men. Exercise may stimulate the expression of proteins involved in apoptosis in skeletal muscle.

9.  Adams, A., Best, T. (2002). The role of antioxidants in exercise and disease prevention. The Physician and Sports Medicine. May30(5): Summary: Excess free radicals have been associated with the diseases of aging including, cancer, heart disease, brain diseases, macular degeneration, and exercise associated muscle damage. Antioxidant supplements such as vitamin C, E, and beta-carotene have been promoted as enhancing exercise and for preventing certain diseases. Because "study results have been contradictory, individual supplement recommendations must be offered with caution. The most beneficial prescription is probably a daily diet containing five to seven servings of fruits and vegetables.”

10.  Ajmani, R. Fleg, J., Demehin, A., Wright, J., et al. (2003). Oxidative stress and hemorheological changes induced by acute treadmill exercise. Clinical Hemorheol Microcirculation. 28(1);29-40.
The researchers studied the acute effect of aerobic exercise on oxidative stress and the flow properties of the blood. Post exercise significant increases were observed inn plasma lipid hydroperoxides and the relative concentrations of plasma fluorescent products associated with red cell peroxidation, and increase in plasma viscosity, and increase in red cell rigidity, and a decrease in erythrocyte sedimentation rate. The findings suggest that acute aerobic exercise induces oxidative damage to red blood cells and adversely affects rheological properties of the peripheral blood.

11.  Gleeson, M., Bishop, N. (2000). Special feature for the Olympics: effects of exercise on the immune system: medication of immune responses to exercise by carbohydrate, glutamine and anti-oxidant supplements. Immunology Cell Biology. Oct;78(5):554-61.
Training and competition surroundings may increase the athlete’s exposure to pathogens and provide optimal conditions for pathogen transmission. Heavy prolonged exertion is associated with numerous hormonal and biochemical changes, many of which potentially have detrimental effects on immune function. Furthermore, improper nutrition can compound negative influence of heavy exertion on immunocompetence. Evidence that high doses of anti-oxidant vitamins can prevent exercise-induced immunosuppression is lacking.

12.  Pearson, R., Ungpakorn, G. and Harrison, G. (1995). Catecholamine and cortisol levels in Oxford college rowers. British Journal of Sports Medicine. Sept;29(3):174-7.
Urinary catecholamines and cortisol levels in two teams of Oxford oarsmen were compared. Adrenaline and cortisol were raised on racing and training days compared to non-training days. Noradrenaline was raised on training days, reflecting longer periods of physical exercise during training.

13. Hamlin, M., Shearman, J., Hopkins, W. (2002). Changes in physiological parameters in overtrained standardbred racehorses. Jul; 34(4):383-8.
Various changes in physiological parameters are associated with overtraining which can be a serious problem for human and equine athletes. The researchers studied the effects of an acute training overload on physiological parameters in 10 standardbred racehorses. Acute overtraining coincided with an increase in blood lactate concentration after the time trial and submaximal test. There were also substantial decreases in bodyweight, plasma cortisol concentration and packed cell volume after the time trial, and in the velocity of heart rate. Parameters that showed no clear cut change with overtraining included maximal and recovery heart rate, basal plasma cortisol, plasma and red cell volume, and markers of skeletal damage. Bodyweight, post exercise blood lactate and plasma cortisol concentrations may all be useful for detecting acute overtraining in equine athletes.

14. Steinacker, J., Lormes, W., Reissnecker, S. and Liu, Y. (2004). New aspects of the hormone and cytokine response to training. European Journal of Applied Physiology. April;91(4):382-91.
Exercise training is associated with peripheral cellular and central cerebral processes, hormonal-neuronal regulation and transmission mechanisms. Glycogen deficiency is associated with increased expression of local cytokines, decreased expression of glucose transporters, increased cortisol and decreased insulin secretion and beta-adrenergic stimulation. Muscle damage and repair processes may involve the expression of inflammatory cytokines (tumor necrosis factor-alpha, TNF-alpha) and of stress proteins. These alterations are influenced by exercise-induced hypercortisolism and by decreased somatotropic hormones. The hypothalamus integrates various error signals and therefore pituitary releasing hormones represent the functional status of an athlete and long-term hypothalamic hormonal and sympathoadrenal downregulation and some of the prominent hormonal signs of prolonged overtraining and performance incompetence syndrome.

15. Shen, W. Zhang, X., Zhoa, G., Wolin, m. et al. (1995). Nitric Oxide production and NO synthase gene expression contribute to vascular regulation during exercise. Medical Science Sports Exercise. Aug;27(8):1125-34.
Nitric oxide is a vasodilator produced under normal physiological conditions primarily by the vascular endothelium lining all blood vessels. The primary stimulus for the production of nitric oxide by the constitutive endothelial nitric oxide synthase found in blood vessels is most likely the shear stress, the frictional force, caused by blood flowing through blood vessels. During exercise there is an increase in cardiac output and redistribution of blood flow to increase blood flow in skeletal muscle and in the coronary circulation. These adjustments provide increased oxygen delivery to support aerobic energy production and to sustain the exercise response. NO may be involved in the regulation of vascular tone in exercising skeletal and cardiac muscle by promoting, enhancing the metabolic vasodilation. In addition, the production of NO capillary endothelium may regulate oxygen consumption by mitochondria through chemical interactions between NO and the iron-sulfur center of these enzymes. Finally, brief exercise training may alter the gene expression for the enzyme, the constitutive endothelial NO synthase, which forms NO and may be part of the vascular adaptation seen after aerobic exercise training. Furthermore, if there is a genetic predisposition to produce NO, as in world class athletes or animals bred to race, NO may contribute to spectacular exercise performance.

16. Poynter, S., and Eikenberry, N. The antioxidant defense system and exercise.
Summarizes articles supporting increased oxidative stress and exercise. Authors conclude that anti-oxidant supplements are ineffective in diminishing oxidative stress related to exercise, but suggest increasing levels of fruit and vegetables in the diet to mitigate free radical damage.

17. Tsopanakis, C. and Tsopanakis, A. (1998). Stress hormonal factors, fatigue, and antioxidant responses to prolonged speed driving. Pharmacology and Biochemical Behavior. July;60(3):747-51.
Seven racecar drivers of national level were examined before, during, and immediately after the trial of speed driving on a test designed to check endurance to stress. Results indicate that as stress levels increase, fatigue and oxidative stress increase.

18. Ginsburg, G., O’Toole, M., Rimm, E., et al. (2001). Gender differences in exercise-induced changes in sex hormone levels and lipid peroxidation in athletes participating in the Hawaii Ironman triathlon. Clinical Chim Acta. March;305(1-2):131-9.
Although exercise reduces the risk of coronary heart disease in men and women, it may, paradoxically, promote free-radical formation, lipid peroxidation and vascular tissue injury. The researchers studied the effects of exercise on men and women to determine if the stress affected them equally during a triathlon. Lipid changes after exercise were similar for men and women. However, the susceptibility of plasma lipids to peroxidation was reduced 61% in men and only 14% in women post race. These changes were not associated with the supplemental use or levels of antioxidants. In addition, in men there was an increase of 58% in the antioxidant sex hormone estradiol and a decrease of 58% in testosterone post race. No significant changes were noted for the two hormones in women. Conclusion: there are significant gender-specific differences in the susceptibility of lipids to peroxidation and in changes in estradiol and testosterone levels as a result of ultra-endurance exercise. These changes may in part explain the salutary effect of exercise on the development of vascular disease.

19. Kraemer, W., Fry, A., Rubin., et al. (2001). Physiological and performance responses to tournament wrestling. Medical Science Sports Exercise. Aug;33(8):1367-78.
The purpose of the study was to investigate the physiological and performance response to a simulated freestyle wrestling tournament after typical weight loss techniques used by amateur wrestlers. Results: lower body power and upper body isometric strength were significantly reduced as the tournament progressed. Tournament wrestling augments the physiological and performance decrements of weight loss and its impact is progressive over two days of competition. The combined effects of these stresses may ultimately be reflected in a wrestler’s ability to maintain physical performance throughout a tournament.

20. Brooks, G., Fahey, T., White, T., and Baldwin, K. (2000)Exercise Physiology. Human Bioenergetics and its applications. #rd. Ed. McGraw Hill Higher Education: New York, New York. P. 808.
“The utilization of O2 in mitochondria is associated with the liberation of free radicals, which present a real threat to mitochondria. Indeed, K.J.A. Davies and colleagues (1982) at the University of California have supplied evidence of mitochondrial damage due to free radical accumulation at the point of fatigue.”

Dangers of Vitamin Isolates

1. McArdle, W., Katch, F., and Katch, V.(2000). Essentials of Exercise Physiology. Lippincott Williams &Wilkins. Baltimore, MD. p. 74.

“British researchers have reported that a vitamin C supplement of 500mg daily for six weeks produced a pro-oxidant effect (increased free radicals) in addition to the expected antioxidant effect on DNA. The excess vitamin C promoted genetic damage by free radicals to the adenine base of DNA, not previously measured in studies of vitamin C’s oxidative properties. Vitamin C in natural form like orange juice does not act as a pro-oxidant."

“Any significant excesses of vitamins function as chemicals (drugs) in the body. For example, a mega dose of water-soluble vitamin C increases serum uric acid levels that precipitate gout in people predisposed to this disease. At intakes greater than 1000mg daily, urinary excretion of oxalate (a breakdown product of vitamin C) increases, accelerating kidney stone formation in susceptible individuals. In iron-deficient individuals, mega doses of vitamin C may destroy significant amounts of vitamin B-12. In healthy people, vitamin C supplements frequently irritate the bowel and cause diarrhea.”

“Excess vitamin B6 may induce liver and nerve damage. Excessive vitamin B2 intake can impair vision, where a mega dose of niacin can act as a potent vasodilator and inhibit fatty acid mobilization during exercise. This could more rapidly deplete muscle glycogen. Folic acid concentrated in supplement form can trigger an allergic response producing hives, light-headedness, and breathing difficulties. Mega doses of vitamin A can induce toxicity to the nervous system, and kidney damage can result from excess vitamin D intake.”

2. Vitamin C May Increase Mortality in Diabetic Women.
http://nutraingredients-usa.com/news/ng.asp?id=56100&n=dh321&c=tcqxewmdlnjffnz

3. Zinc and Copper buildup may cause Alzheimer’s Disease. Medinew.com. September 12, 2004. “In the view of Dr. Ashley Bush of Harvard Medical School, Alzheimer’s Disease is caused by a copper and zinc buildup in the brain. He believes that accumulated copper and zinc mix with beta amyloid in the brains of Alzheimer’s patients and oxidize, thereby destroying nerve cells.”

4. The Dangers of Too Much Vitamin A. Doctors are warning that freely available dietary supplements contain 25,000 IU of vitamin A – more than double the 10,000 IU recommended by the National Academy of Sciences Institute of Medicine. Too much vitamin A can be harmful and result in liver and nerve damage, bone and joint pain, bone loss, and birth defects. Vitamin A deficiency is not a problem in the US.

5. Dixon, Suzanne. Review of article published in Jouranl of the National Cancer Institute investigating zinc supplements and prostate cancer. Summary: study indicates that taking more than 100 mg of supplemental zinc increases prostate cancer risk.

6. Haber, D. (2003). Health Promotion and Aging. New York: Springer Publishing
Summary: Nutritional intake declines with age. Absorption of important nutrients decreases with age. Problems with vitamin isolates. “There are good reasons to be more cautious taking dietary supplements than the general public appears to be. Most dietary supplements are narrowly targeted while the nutrients in foods work in synergy. Phytochemicals are an example of this distinction. There are recently discovered chemical compounds found in abundance in fruits and vegetables, which seem to exert powerful synergistic effect in cancer prevention. These compounds are presently impossible to replicate in pill form. In addition, people on medication need to be careful with taking dietary supplements. For instance someone taking coumadin, a blood thinning medication, should avoid vitamin K and also avoid several herbs like gingko biloba. Antioxidants are found primarily in fruits and vegetables. Few Americans get adequate servings of fruits and vegetables.

7. Schneider, E. Miles, E., (2003) Ageless. St. Martin Press. “Many multivitamins contain the potent oxidants (as opposed to ant oxidants) iron and copper which may speed cellular aging and contribute to the development of arterial plaque … Another problem with multivitamins is all the other stuff that manufacturers throw in as added bait for you to buy them, from plant extracts such as ginseng, with no known biological effects, to untested, potentially harmful additions like the so-called fat-burner chromium picolinate … The pill you are taking, for example, may contain less than the label professes – or more, including contaminants.” p. 23. 

8. Victoroff, J. (2002). Saving your brain. New York: Bantam Books. Excess zinc could damage the brain. Antioxidant isolates such as vitamin C and E can actually undercut the benefits of cholesterol lowering drugs. pp. 210-245

9. Basu, T., Sedgwick, G. (2002) Niacin in non-physiological doses causes hyperhomocysteinaemia in Sprague-Dawley rats. British Journal of Nutrition. Feb; 87(2):115-9.
Summary: niacin is often prescribed as a natural alternative to reducing cholesterol. This study found that niacin therapy created hyperhomocycteineaemia and was accompanied by a significant decrease in plasma concentrations of B6 and B12, which are cofactors for the metabolism of homocysteine. This is of great concern because hyperhomocysteineaemia is considered an independent risk factor for arterial occlusive disease.

10. Sastre, Juan. The IX biennial meeting of the international society for free radical research, Sao Paulo, Brazil, Sept 7-11, 1998. Meeting Report. Free Radical Res. Vol 30, 99. 329-339.
Summary ; “Free radial detection and biomarkers”. Dr. Kalyanaraman reported that superoxide generation by endothelial nitric oxide synthase is enhanced by flavins, but abolished by concomitant addition of L-arginine and tetrahydrobiopterin.

11. Lenhardt, S. et al. (1999). Vitamins for the management of cardiovascular disease: A simple solution to a complex problem? Pharmacotherapy. 19(12): 1400-1414.
Summary: Investigated the role of B vitamins and antioxidants and cardiovascular disease. “ Data regarding antioxidant vitamins for the management of cardiovascular disease are somewhat confusing. Although Vitamin E appears to decrease the risk of nonfatal myocardial infarction in patients with atherosclerosis, no benefit has been shown for preventing fatal myocardial infarction, and it may, in fact, increase overall mortality risks. In addition, effects of long-term vitamin E supplementation are not known. Beta carotene should not be prescribed as it may increase mortality”

12. Dixon, S.(2003). Summary of article in Cancer Epidemiological Biomarker Prevention, 2003;12(4):350-358.
Summary: “This study indicates that beta-carotene supplements negate (cancel out) the beneficial cancer protective effect of fruits and vegetables in people who smoke.”

13. January 13, 2004. Varying doses in coenzyme Q10 products.  
“Health professionals are being cautioned about the strength discrepancies of some Coenzyme Q10 products. A patient can go from a zero dose to 175% dose just by switching brands.”

14. Schoonover, L. (2001). Oxidative stress and the role of antioxidants in cardiovascular risk reduction. Progressive Cardiovascular Nurse. 16(1):30-32.
Summary: The contribution of free radicals and vascular damage is well accepted. The impact of dietary supplementation and treatment with antioxidant vitamin isolates remains controversial. The injury caused by oxidative stress can affect all organ systems. Oxidation of LDL cholesterol is a key factor in the development of atherosclerosis. Free radicals appear to be involved throughout this process. Reports of clinical studies of antioxidant vitamin isolate supplementation have documented controversial and contradictory outcomes. Due to the lack of conclusive data in the setting of primary prevention of cardiovascular events and the potential detrimental effects of vitamin isolates, The American Heart Association recommends consumption of antioxidant rich foods as opposed to vitamin supplementation.

15. Vitamin A supplementation linked to increased risk for hip fracture. www.medscape.com/viewarticle/470046 Use of vitamin A supplementation by postmenopausal women is a marker for excessive intake of vitamin A, which is associated with a 20% increase in risk for hip fracture, according to a study reported at Preventative Medicine 2004.

16. Journal of the American Nutraceutical Association. www.americanutra.com
46 natural food products were tested for ORAC units. The supplements ranged from 16 to 3985 ORAC units. There are no standards for the antioxidant capacity of natural products and thus little assurance of a high quality product according to chemist Ron Prior at the USDA Human Nutrition Research Center at Tufts. A single serving of fresh fruits and vegetables supplies an average of 300 to 400 ORAC units. By contrast, 28 of the natural products tested had only 300 ORAC units.

17. Kaack, K., Austed, T. 1998. Interactionn of vitamin C and flavonoids in elderberry during juice processing. Plant foods and Human Nutrition. 52(3):187-98.
Summary: anthocyanin and quercitin content of fruits including elderberry can be subject to oxidation during processing and juicing if precautions are not taken.

18. Negative effects of zinc supplements on early mental development.
http://nutraingredients-usa.com/news/news-NG.asp?id=23509
Study reported in The Lancet suggests that pregnant women in developing countries who are given zinc supplements may in fact be harming their children’s chances during early mental development.

19. Kirchheimer, S. Reviewed by Nazario, B. M.D. WebMD Medical News, may 3, 2004 . A study published in the Journal of Clinical Investigation. Do antioxidants contribute to heart disease?
“Taking antioxidant vitamins may actually contribute to heart disease by boosting production of bad cholesterol. Fisher's team found that vitamin E prevented normal breakdown of fats in rat and mouse liver cells. In other words, these antioxidants prevented the liver from destroying fats such as VLDL, the precursor to bad LDL cholesterol. The antioxidant supplements caused more VLDL to be present.

20. Athlete supplements fail to meet quality standards. http://nutraingredients-usa.com/news/ng.asp?n=dh117&c=tcqxewmdlnjffnz&id=51641
 “Some supplements targeted at professional athletes contain banned substances which are not listed on their labels. A team from ConsumerLab.com also found that products with unlisted banned substances are not limited to performance enhancers but include products ranging from multivitamins to sleep aids. The most common unlisted substances were stimulants such as ephedrine and caffeine."

 

Section 2: Chokeberry

Chokeberry anti-inflammatory effects

1. Borissova, P., Valcheva, S., Belcheva, A. (1994). Anti-inflammatory effect of flavonoids in the natural juice from chokeberry, rutin and rutin-magnesium complex on an experimental model of inflammation induced by histamine and serotonin. Acta Physiol Pharmacol Bulg. 20(1);25-30.
Summary: Chokeberry juice was compared to rutin and rutin-magnesium complex as an anti-inflammatory agent. The results of the tests showed that the anthocyanin flavonoids form the natural juice of chokeberry exerted more pronounced anti-inflammatory than either rutin or rutin-magnesium complex.

2. Zheng, W., Wang, S. (2003). ORAC capacity of phenolics in blueberries, cranberries, chokeberries, and lingonberries. Journal of Agriculture and Food Chemistry. Jan 15;51(2):502-9.
Summary: Phenolics such as quercitin and cyaniding in these berries had highly effective radical scavenging structures.

Chokeberry (Aronia) anti-oxidant ability and absorbability

1. Kahkonen, M., Hopia, A., Vuorela, H., Rauha, J., Pihlaja, K., Kujala, T., Heinonen, M. (1999). Antioxidant activity of plant extracts containing phenolic compounds. Journal of Agricultural and Food Chemistry. Oct;47(10):3954-62.
Summary: the antioxidant activity of 92 phenolic extracts from edible berries and nonedible plant materials was examined. Among edible plant materials remarkable high antioxidant activity and high total phenolic content were found in berries, especially chokeberry and crowberry.

2. Orechovich Institute of biomedical Chemistry.( 2003)Antioxidant effect of chokeberry leaf extract. Vopr Medical Khim . March-April;49(2):165-76.
Summary: tested antioxidant power of chokeberry and found that the extract contained a powerful combination of antioxidants with different free radical scavenging activities.

3. Pawlowicz, P. et al (2000). Administration of natural anthocyanins derived from chokeberry retard idiopathic and pre-eclamptic origin. Ginekol Pol. Aug;71(8):848-53
Summary: demonstrates ability of chokeberry to control oxidative stress during pregnancy complicated by intrauterine growth retardation.

Chokeberry: Arterial Protection: Blood pressure, blood clots, atherosclerosis, NO production

1. Kowalczyk, E., Kopff, A., Niedworok, J., Kopff, M., Jankowski, A. (2002) Anthocyanins-an adjunct to cardiovascular therapy? Kardiology Poland.
Oct; 57(10):332-6.
Summary: anthocyanins are one of the most important water-soluble plant pigments. They belong to flavonoids and have antioxidant and anti-inflammatory properties and, therefore, may be potentially used to combat oxidative stress, frequently present in cardiovascular diseases. This study aimed to assess the effects of anthocyanins from chokeberry on some parameters of oxidation reduction balance in animals. The tests showed that the anthocyanins from chokeberry decrease lipid peroxidation, which may be potentially used to combat oxidative stress (and diseases of the brain).

2. Benz, D., Cadet, P., Mantione, K., Zhu, W., Stefano, G. (2002). Tonal nitric oxide and health – a free radical and a scavenger of free radicals.
Summary: Basal/tonal NO production helps maintain particular microenvironments, i.e., vascular. Besides NO’s function in controlling the activation state of various tissues such as immune cells, its presence appears to modulate free radical levels in these same tissues and indeed these processes may be one and the same. Thus by being a free radical, along with its ability to scavenge free radicals, NO is placed in a pivotal regulatory position. We surmise that in the absence of adequate NO release other free radicals may go unchecked and therefore, initiate tissue damage. Furthermore, under these circumstances, pro inflammatory events will occur due to heightened cell sensitivity and a diminished control of NF-kappaB. In an excess situation, and one without an appropriate circumstance, i.e., microbial action, NO may become the harmful agent. Hence, balancing basal NO production in body compartments may represent a fundamental process in maintaining general, long-term health.

3. Bell, David R., Phd, and Gochenaur, Kristin, B.S. (2002). Characterization of coronary arterial reactivity of berry anthocyanins. Presentation at American Physiological Society (APS) annual meeting in New Orleans, LA.
Summary: the researchers looked at the effects of nitric oxide produced by endothelial cells lining the inner surface of blood vessels. Nitric oxide is a strong relaxing agent of the smooth muscle found in arteries. Nitric oxide plays a major role in keeping blood pressure from becoming dangerously high. It also helps to prevent spasms in blood vessels. Nitric oxide also shows the ability to inhibit the development of blood clots as well as the early processes involved in developing atherosclerosis. The researchers found that chokeberry extract was the most potent in helping relax arteries, aid blood flow, and protect coronary arteries from free radical injury (oxidative stress). They concluded that chokeberry extract in concentrations likely to be found following reasonable ingestion of this compound, could help maintain arterial function.

Chokeberry and diabetes

Simeonov, S., Botushanov, N., Karahanian, E. Oavlova, M., Husianitis, H., Troev, D., (2002). Effects of chokeberry juice as part of the dietary regimen in patients with diabetes mellitus. Folia Med(PlOvdiv) 44(3):20-3
Summary: Accumulated data by the researchers illustrated the hypoglycemic potential of chokeberry juice. While the precise mechanism is unknown, its beneficial effects make it a valuable adjunct to the dietary treatment of patients with diabetes mellitus.

APEXChokeberry and diabetes

Maslov, D., Ipatova, O., Abakumova, O et al. 2002. Hypoglycemic effect of an extract from Aronia Melancarpa leaves(Chokeberry). Vopr Medical Khim. May-June;48(3):271-277. The action of the extract to blood glucose levels was investigated. It was shown that incorporated into drinking water and administered intraperitoneally, the extract significantly reduced the blood glucose level of streptozotocin (STZ) in diabetic and normal rats.

Chokeberry anti-tumoric benefits

Christidou, M., Rooprai, HK., Rucklidge, G., Davis, D., Clayton, PR., Zicha, D., Pilkington, GJ., The effect of three berry flavonoids on malignant human brain tumor cell lines in vitro.
Summary: Tested a hypothesis that naturally occurring flavonoids from berries may serve as potent anti-cancer agents in the management of brain tumors. Flavonoids are ubiquitous in fruits, plants, and vegetables. Extracts of chokeberry (Aronia Melanocarpa), bilberry (Vaccinium Myrtillus) and elderberry (Sambucus NigraL.) are composed of phenolic acids, catechins, flavones, and anthocyanins. The aim of the study is to evaluate the effect of the three berry extracts on various parameters in vitro. Increased cell death was observed with chokeberry and bilberry, which was confirmed by flow cytometry.


Section 3: Elderberry

Elderberry Cardiovascular protection

1. HerbalGram. 2000;50:55 American Botanical Society
“At the scientific heart of the elderberry boom, Doctors Werner Pfaqnnhauser and Michael Murkovic at Austria’s University of Graz research the biological activity of elderberry anthocyanins. Their studies show that elderberry anthocyanins are absorbed into plasma and possess in vitro antioxidant activity. These findings corroborate the work of Cao and Prior at Tufts University, who have tracked anthocyanins in human plasma after ingestion. Pfannhauser and Murkovic have further found that elderberry extract reduces oxidation of LDL cholesterol. While cholesterol is an essential component manufactured in the liver, oxidation of LDL cholesterol is implicated in atherogenesis, thus contributing to cardiovascular disease, especially heart attacks and strokes. Both researchers express optimism that elderberry and its extracts may be used for cardio protective purposes in the future. Additional research conducted at Tufts University shows that elderberry anthocyanins protect vascular epithelial cells against oxidative insult, thereby helping to prevent changes in these cells, which are associated with vascular disease.

2. Youdin, K., Martin, A., Joseph, J. (2000). Incorporation of the elderberry anthocyanins by endothelial cells increases protection against oxidative stress. Free Radical Biological Medicine. July 1;29(1):51-60.
Summary: The purpose of the study was to investigate the ability of endothelial cells to incorporate anthocyanins from elderberry and to examine their potential benefits against various oxidative stressors. The results showed that the enrichment of endothelial cells with elderberry anthocyanins conferred significant protective effects against the following oxidative stressors: hydrogen peroxide, AAPH, and FeSO(4)/ascorbic acid. These results show for the first time that vascular endothelial cells can incorporate anthocyanins into the membrane and cytosol, conferring significant protective effects against oxidative insult. These findings may have important implications on preserving endothelial cell function and preventing the initiation of endothelial cell changes associated with vascular diseases.

Elderberry Anti-oxidant ability and absorbability

1. Herbalgram. 2000. 50:55. The Journal of the American Botanical Council
In Karlsruhe at Germany’s Bundesforschungsanstalt research center for food, scientists conduct studies on dietary agents that can reduce oxidation and protect cells. According to research led the center’s director, Dr. Gerhardt Rechkemmer, anthocyanins found in elderberries possess appreciably more antioxidant capacity than either Trolox or vitamin C. The work conducted there supports previous research conducted at Graz, Austria showing that anthocyanins possess significant free radical scavenging capacity.”

2. Milbbury, P., Cao., G., Prior, R., Blumberg, J. (2002). Bioavailability of elderberry anthocyanins. Mechanics of Aging Development. April 30;123(8):997-1006.
Summary: “Considerable epidemiological evidence suggests a link between the consumption of diets rich in fruits and vegetables and a decreased risk of cardiovascular disease and cancer. Anthocyanins have received attention as important dietary constituents that may provide health benefits and contribute antioxidant capacity beyond that provided by essential micronutrients such as ascorbate (Vitamin C), tocopherols (Vitamin E), and Selenium. The emergence of renewed interest by industrial countries in traditional herbal medicines and the development of ‘functional foods' are stimulating the need for more information regarding the bioavailability and efficacy of plant polyphenols. Flavonoids represent a numerous group of secondary plant metabolites. Anthocyanins, potent flavonoid antioxidants widely distributed in fruits and vegetables, normally occur in nature as glycosides, a form not usually considered as bioavailable. We examined the bioavailability and pharmacokinetics of anthocyanins in humans. Anthocyamins were detected as glycosides in both plasma and urine samples. The elimination of plasma anthocyanins appeared to follow within four hours after feeding. The current findings support the idea that elderberry anthocyanins are well absorbed in humans.”

APEX Elderberry, anti-viral activity including flu viruses

1. HerbalGram. 2000;50:55 Journal of the American Botanical Council
“An oft cited Israeli study (Turpin, J. et al. antiviral evaluation of elderberry extracts and standardized powder. Southern Research Institute, Frederish MD. Unpublished, 2000) found that in vitro elderberry extract reduced hemogglutination of red blood cells and inhibited replication of a number of strains of influenza A and B in cell cultures. In the same paper, administration of elderberry extract to 27 patients with influenza shortened the duration of flu symptoms. In a Swiss study, elderberry extract inhibited replication of avian influenza virus in a human breast cancer cell line. And in vitro studies conducted by the Southern Research Institute using elderberry extracts from Artemis Intl showed inhibition of herpes virus in cell cultures.”

2. Rosenfeld, I. (2004) Dr. Isodore’s Breakthrough Health. Rodale. P. 66.
“Elderberry has been used for centuries to treat everything from respiratory tract infections to gastrointestinal symptoms to depression. … Now comes word from some credible scientists that elderberry really does work against the flu. Researchers at the University of Oslo School of Medicine in Norway have found that an extract from the black elderberry(Sambucus Nigra) reduces symptoms and duration of flu types A and B. Flu patients given this herbal extract recovered in three days as compared to seven days in those taking placebo. Apparently, an ingredient in elderberry attacks the flu virus and prevents it from attaching to the body’s cells and making us sick.”

3. Zakay-Rones, Z., Varsano, N., Zlotnik, M., Manor, O., Regev, L., Schlesinger, M., and Mumcuoglu, M. (1995). Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L) during an outbreak of influenza B Panama. Journal of Alternative and Complimentary Medicine. 1(4) Winter. Pp. 361-369.
Summary: A standardized elderberry extract reduced hemagglutination and inhibited replication of human influenza viruses type Ashandong, A/Beijing, A/Texas, A/ Singapore, B/Panama, B/Yamagata, B/ Ann Arbor and animal strains from Northern European swine and turkeys. A placebo controlled, double blind study was carried out on a group of individuals living in an agricultural community during an outbreak of influenza B/Panama in 1993. Fever, feeling of improvement, and complete cure were recorded during 6 days. A significant improvement of the symptoms including fever was seen in 93.3% of the cases treated with the extract within two days versus six days in those who did not take the extract. A complete cure was achieved for 90% of the treated group within two days versus six or more in the untreated group. Considering the efficacy of the extract in vitro on all strains of influenza tested, the clinical results and absence of side effects suggest that this extract could offer a possibly safe treatment for influenza type A and B.

4. Konlee, M. (1998). A new triple combination therapy. Posit Health News. Fall;(17):12-14. A theory for the ability of elderberry to inhibit symptoms of a number of strains of influenza is that elderberry renders viruses nonfunctional by staining and coating them.

APEXElderberry and Stress Reduction

1. Letiner, G. et al(2000). Stress induced electrolyte and blood gas changes with and without a six-day oral treatment with elderberry (Sambucus nigra L.) concentrate. Magnesium-Bulletin 22(3): 72-76
Summary: APEXElderberry effects on Stress Parameters. Results: oral consumption of APEXElderberry leads to significant decreases in stress related parameters. A number of parameters are commonly used to measure postoperative stress in critically ill patients in intensive care. Dr. Porta has found that stress-induced physiological changes, monitored by these same parameters, are correlated with an increase in the presence of stress hormones (catecholamines). Parameters include; blood gases, parameters of carbohydrate metabolism, electrolyte changes and changes in white blood cells. Participants took 4 APEXElderberry capsules and 35 ml of APEXElderberry Concentrate (equivalent of 0.65 kg of fresh elderberries) for six days. Individuals were subjected to an increasing cycle ergometry test to establish mild stress parameters prior to the APEXElderberry regime and again after six days. Dr. Porta suggested that the daily consumption of APEXElderberry could help limit the physiological effects of stress. APEXElderberry was found to:
   a. reduce blood glucose levels induced by stress
   b. increase metabolism(shown by an increase in metabolic rate), which may help to reduce catecholamine levels
   c. increase cellular oxygen consumption(shown by a lowering of pO2 in spite of faster breathing and high pH and a drastic decrease in ionized magnesium)

2. HerbalGram. 2000;50:55 American Botanical Council. “Of all the discoveries related to elderberry, the most surprising is the apparent capacity of elderberry and its anthocyanin-rich extract to reduce stress. This effect was discovered by Austrian endocrinologist Dr. Sepp Porta, who conducted stress studies using elderberry concentrate on a group of volunteers. In the study, various biomarkers of stress, including glucose, magnesium and other plasma chemical levels were analyzed. What he found was that elderberry has an extraordinary effect for reducing stress. Most notably, oral ingestion of elderberry extract resulted in increased glucose uptake, a pointed fall in ionized magnesium, and a significant increase in basal granulocytes. Porta also found that daily intake of elderberry extract significantly shortened recovery time from physical exertion.”

APEXElderberry: Athletic performance and recovery time

Standardized APEXElderberry Liquid Pilot Studies.
Summary: Standardized APEXElderberry Liquid is an elderberry concentrate with elevated levels of anthocyanin, catechins, and other polyphenolics. The objective of the following pilot studies was to determine specific biomedical areas where APEXElderberry has a positive health benefit. The following research was done by Dr. Sepp Porta, from the University of Graz in Austria and the Institute of Applied Stress in Bad Radkersburg, Austria, in collaboration with the United States Air Force and the Institute Sechonov in St. Petersburg, Russia. The first three studies outlined below clearly show that consumption of BerryBoost APEXElderberry prior to exercise leads to decreased production of lactic acid.

In the first three studies, the magnesium concentration in the APEXElderberry-treated groups was lowered. This may be explained by the fact that in blood samples only free or ionized Mg is measured, not bound forms. Proteins are known to absorb or bind ionized Mg as they are produced and are able to release it when needed. This fact is the connecting piece to the fourth study in the series, which was done with animals. The latter showed significant increase in liver activities when APEXElderberry was consumed, which is connected with higher protein production. When results from all of the trials are reviewed together, Dr. Porta proposes two things: (1) APEXElderberry consumption prior to exercise prolongs oxidative phosphorylation and (2) at least one of the APEXElderberry’smodes of action is based on its ability to activate the liver.

Study 1. APEXElderberry Effects on Stress Parameters. Results: oral consumption of APEXElderberry leads to significant decreases in stress related parameters. A number of parameters are commonly used to measure postoperative stress in critically ill patients in intensive care. Dr. Porta has found that stress-induced physiological changes, monitored by these same parameters, are correlated with an increase in the presence of stress hormones (catecholamines). Parameters include; blood gases, parameters of carbohydrate metabolism, electrolyte changes and changes in white blood cells. Participants took 4 APEXElderberry capsules and 35 ml of APEXElderberry Concentrate (equivalent of 0.65 kg of fresh elderberries) for six days. Individuals were subjected to an increasing cycle ergometry test to establish mild stress parameters prior to the APEXElderberry regime and again after six days. Dr. Porta suggested that the daily consumption of APEXElderberry could help limit the physiological effects of stress. APEXElderberry was found to:
   a. reduce blood glucose levels induced by stress
   b. increase metabolism (shown by an increase in metabolic rate), which may help to reduce catecholamine levels
   c. increase cellular oxygen consumption (shown by a lowering of pO2 in spite of faster breathing and high pH and a drastic decrease in ionized magnesium)
Along with its highly antioxidant properties, this data supports the use of APEXElderberry in products designed to mediate stress.

Study 2. APEXElderberry effects in conjunction with exercise. Results: Dr. Porta tested semi-professional runners from the Austrian Army Sport Group and found that oral consumption of APEXEldeerberry prior to exercise leads to significantly less increase in lactate accumulation during exercise. A single dose (40ml) of Standardized APEXEldeerberryLiquid was given to 7 semi-professional runners, prior to 1 hour of submaximal jogging. Nine untreated runners served as control group. Prior to APEXElderberry ingestion and after the run, the participants’ blood gases, PH, sodium, calcium, magnesium, blood glucose and lactate concentrations were determined. Dr. Porta found that consumption of APEXElderberry prior to exercise led to:
   a. significantly less increase in lactate concentrations
   b. no significant decrease in pCO2, which in turn did not increase pO2 and O2 saturation
   c. a significant decrease in the ionized magnesium
   d. The results point towards an increase of oxidative phosphorylation during exercise caused by APEXElderberry supplementation. The onset of anaerobic, less efficient glycolysis also seems to be significantly postponed. Therefore, metabolic reserves of the individual runners seem to be strengthened considerably by a single acute pre-exercise APEXElderberry application production by the liver.

Study 3. APEXElderberry effects in a clinical crossover trial. Results: Dr. Stepp tested 10 male subjects in a crossover experiment and found that oral consumption of APEXElderberry prior to exercise leads to significantly increased buffer capacity and therefore much better stress compatibility. Prior to exercise blood was drawn from the 10 male subjects and analyzed for the same parameters described in study 2. The subjects then worked out on an ergometric cycle at 150 watts for ten minutes. After resting for three minutes, blood was again drawn for analysis. Four hours later, the same participants were subjected to the same procedures, except this time the participants ingested a single acute dosage (40mL) of standardized APEXElderberry liquid fifteen minutes prior to riding the cycle, but after the first blood sampling. Dr. Porta found that consumption of APEXElderberry prior to exercise confirmed the results he obtained in study 2, namely:
   a. significantly less increase in lactic acid concentration
   b. more pronounced decrease in pH (even though the lactic acid increased less)
   c. ionized magnesium was lowered

The human body produces energy through two main systems:
   a. with oxygen via oxidative phosphorylation. This is by far the most effective way for sufficient and quick delivery of energy. But during oxidative phosphorylation, free radicals are produced. Dr. Porta stated that when a high enough concentration of free radicals is produced, then the system supplying energy changes to one without oxygen.
   b. Without oxygen via anaerobe glycolis. This is a much slower and less effective system. Since oxygen is not involved in the reaction, free radicals are no longer produced. But, on the other hand, there is a larger build up of lactate, which makes muscles tired. If the exercise is not stopped soon, the acidification in the cells increases and the muscles get sore and stiff.

As one gets into better shape, oxidative phosphorylation occurs for a longer time period and anaerobic glycolysis is therefore postponed. APEXElderberry not only works as an antioxidant neutralizing free radicals (produced during exercise), but this research also shows it aids in prolonging oxidative phosphorylation and thus postponing anaerobic glycolysis. In other words, consuming APEXElderberry prior to exercise leads to more energy being available. This allows the body to work harder and longer, while delaying the signs of fatigue.

Study 4. APEXElderberry effects in an animal study. Results: Professor Porta found that oral consumption of APEXElderberry by rats leads to increased liver activation. A group of 2-year old rats was given 5mL/day of Standardized APEXElderberry Liquid for 10 days. Part of the group was subjected to an ergometric load while the other was not. Afterwards, the animals were weighed, sacrificed, histological evaluation was done on the organs, and serum samples were collected for further analysis. Dr. Porta found that the daily consumption of APEXElderberry led to:
   a. increased nitrate and malondialdehyde levels in the blood
   b. increased urea and uric acid in the blood

Nitrates and malondialdehyde increase when free radicals are neutralized. An increase in their concentrations is therefore a sign of antioxidant reaction due to the presence of APEXElderberry. Nitrate is also important in blood circulation, since it has a vasodilatory effect on blood vessels. In fact, many common heart disease medicines are based on nitrate. The production of uric acid and urea are indicators of increased nitrogen metabolism. They also found the following signs of increased liver activity:
   a. increased liver protein production
   b. significant increase in liver enzyme activity such as GPT and GGT; increased activity of cholinesterase
   c. increased apoptosis in the liver, thus renewing non-functional old cells and therefore increasing functionality. Although increases in protein production and liver enzyme activity (such as GPT and GGT) may be a sign of liver damage, when combined with the increased activity of cholinesterase, the four results together prove that the liver is actually increasing its metabolism. Cholinesterase is an important indicator of liver activity, and when the liver is damaged the activity of this enzyme also decreases.

APEXElderberry, liver metabolism, and improved liver function

APEXElderberry effects in an animal study. Results: Professor Porta found that oral consumption of APEXElderberry by rats leads to increased liver activation. A group of 2-year old rats was given 5mL/day of Standardized APEXElderberry liquid for 10 days. Part of the group was subjected to an ergometric load while the other was not. Afterwards, the animals were weighed, sacrificed, histological evaluation was done on the organs, and serum samples were collected for further analysis. Dr. Porta found that the daily consumption of APEXElderberry led to:
   d. increased nitrate and malondialdehyde levels in the blood
   e. increased urea and uric acid in the blood

Nitrates and malondialdehyde increase when free radicals are neutralized. An increase in their concentrations is therefore a sign of anti oxidant reaction due to the presence of APEXElderberry. Nitrate is also important in blood circulation, since it has a vasodilatory effect on blood vessels. In fact, many common heart disease medicines are based on nitrate. The production of uric acid and urea are indicators of increased nitrogen metabolism. They also found the following signs of increased liver activity:
   a. increased liver protein production
   b. significant increase in liver enzyme activity such as GPT and GGT; increased activity of cholinesterase
   c. increased apoptosis in the liver, thus renewing non-functional old cells and therefore increasing functionality.
Although increases in protein production and liver enzyme activity (such as GPT and GGT) may be a sign of liver damage, when combined with the increased activity of cholinesterase, the four results together prove that the liver is actually increasing its metabolism. Cholinesterase is an important indicator of liver activity, and when the liver is damaged the activity of this enzyme also decreases.

Elderberry anti-tumoric benefits

Hou, D. (2003). Potential mechanisms of cancer chemoprevention by anthocyanins; Current Molecular Medicine. 3:149-159
Epidemiological studies support the thesis that ingestion of fruits and vegetables containing anthocyanins lower the risk of cardiovascular disease and improvement of visual function. This article summarized the most recent findings regarding anthocyanins and cancer chemoprevention.
“Anthocycanins can be directly absorbed and distributed in the blood.”

Potential effects of anthocyanins on health:
1. Antioxidation: anthocyanins are powerful antioxidants and can re-establish plasma antioxidant capacity and decrease vitamin E deficiency in cases of low vitamin E intake.
2. Anti-carcinogenesis: Anthocyanins, particularly cyanidin (present at high levels in elderberry and chokeberry) showed reduced lesion development in colons of rats as well as other anti-tumoric activities.
3. “Apoptosis plays an important role in elimination of seriously damaged cells or tumor cells by chemo preventative agents.” Anthocyanins, particularly cyanidin (present at high levels in chokeberry and elderberry) induced apoptosis.
4. Anti-mutagenicity: “Cyanadin showed stronger activity of anti-mutagenicity than peonidin. Based on additional studies with enzyme activity, the authors concluded that anthocyanins protected against the mutagenisis.”
5. Anti-inflammatory activity: “cyanidin showed better anti-inflammatory activity than aspirin.” The anti inflammatory activity of cyanadin was comparable to that of naproxen, which is a nonsteroidal anti-inflammatory drug.
6. Anthocyanins may reduce the oxidative stress of nitric oxide and increase the protective effects against cardiovascular and chronic inflammatory disease.
7. Potent inhibitor of the epidermal growth-factor receptor (EGFR).”EGFR is one of cell-surface proteins conveying growth stimulatory signals across the cell membrane. EGFR is involved in the aberrant growth of many types of human cancer cells. Meiers et al found that cyanidin and delphinidin (contained in black currant) inhibited the tyrosine kinase activity of EFGR and suggest that cyaniding and delphinidin may be potent inhibitors of EGFR.”
8. Potent inhibition of tumor cell invasiveness. Metastasis is the major cause of cancer mortality. Delphinidin (contained in black currant) may inhibit tumor cell invasiveness.
9. Estrogenic activity. Test results “suggest that anthocyanins exert estrogen activity, which might play a role in altering the development of hormone-dependent adverse effects.”
10. Bioavailability. Most results indicated that anthocyanins were directly absorbed and bioavailable to humans. Anthocyanins can be absorbed within two hours of ingestion. Other tests show plasma anti oxidant capacity was significantly elevated within thirty minutes. Another test showed that anthocyanins are absorbed in their unchanged glycated forms in elderly women.
11. Tolerability and Safety. “ a highly purified extract from V. myrtillus berries containing 36% anthocyanins has been used to test the tolerability and safety of anthocyanins in animals.” Extremely high doses given over six months to mice and rats and dogs did not cause death or any toxic effects and did not affect fertility in rats. The extract did not show any teratogenic effect and mutagenic activity. “ The clinical safety was confirmed in a post marketing surveillance study. Most persons took 160 mg twice daily for six months. In most cases, the extract was well or very well tolerated. Only 4% of persons complained of side effects, mainly gastrointestinal or concerning skin and cutaneous annexes, and nervous system.”

Conclusion: tests support the antioxidant, anti mutagenicity, anti inflammatory, anti carcinogenis and apoptosis induction of malignant cells, in cancer chemo prevention. The studies generally relied on very high doses supporting the idea that results are dose dependent.

Roy, S., Khanna, S., Alessio, H., Vider, J., Bagchi, M., Sen C. (2002). Anti-angiogenic property of edible berries Free Radical Research, Sept;36(9):1023-31.
Summary: “ Recent studies show that edible berries may have potent chemo protective properties. Vascular endothelial growth factor(VEGF) plays a crucial role for the vascularization of tumors. The vasculature in adult skin remains normally quiescent. However, skin retains the capacity for brisk initiation of angiogenesis during inflammatory skin diseases such as psoriasis and skin cancers. We sought to test the effects of multiple berry extracts on inducible VEGF expression by human HaCaT keratinocytes. Six berry extracts (wild blueberry, bilberry, cranberry, elderberry, raspberry seed, and strawberry and grape seed proanthocyanidin extract were studied. Antioxidant capacity was tested using ORAC. Cranberry, elderberry, and raspberry seed were observed to possess comparable ORAC values. Each of the berry extracts sampled significantly inhibited both H202 as well as TNF alpha induced VEGF expression by the human keratinocytes. This effect was not shared by other antioxidants such as alpha-tocopherol (Vitamin E) but was commonly shared by pure flavonoids. Matrigel assay using human dermal microvascular endothelial cells showed that edible berries impair angiogenesis.

 

Section 4: Black Currant

Black currant Health Benefits

1. Anti oxidant more powerful than green tea extract
Yoshiki, Y., Okubo, K., Matsumoto, H. (2001)Biotechnology and AgroChemistry. Proceedings of Japan Society for Bioscience . 3M5a15, p. 289
The study tested APEXBlackcurrant and showed polyphenols in the berries demonstrated stronger antioxidant power than bilberry or green tea extract in vitro.

2. Improved blood circulation
Millet, J., ChiCaud, P., Legendre, C., Fontaine, M., (1984). Journal of Pharmacology. 15: p. 439-445.
Factors such as vasodilation, suppressed capillary permeability, and reduction in blood viscosity contribute to improvements in blood circulation. These factors together relieve asthenopia as well as various symptoms associated with peripheral circulation disturbance such as stiff shoulder and coldness. The improvement effect of blackcurrant juice on membrane permeability of blood has been proved by this study in monkeys on high fat diets and on humans.

3. Black currant improved vision
Nakaishi, H., Matsumoto, H. Tokunaga, S. Hyrayama, M. (2000) Alternative Medicine Review. 5,553-562
The effects of black currant anthocyanins have been studies in Europe since World War II when the Royal Air Force ate black currant jam to improve night vision. APEXBlackcurrant was tested in a leading research facility and found to be effective in mitigating the hypertonicity that results from prolonged periods in front of a computer. With a double-blind placebo-controlled study with twenty-one healthy adults, the effect of APEXBlackcurrant on false myopia after two hours of computer work. False nearsightedness was evident in the placebo group while the control group receiving the APEXBlackcurrant extract did not show any evidence of nearsightedness.

Dark adaptation was also studied using a double-blind placebo-controlled group. When given APEXBlackcurrant for 14 consecutive days, the control group showed improvement in dark adaptation.