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by Steve Myers
Boomers and pre-Boomers live under the looming threat of degenerative diseases, such as heart disease, cancer, Alzheimer’s, diabetes and osteoporosis. Lifestyle, diet and the process of aging all partially determine the development and progression of these diseases, giving older generations a fighting chance at a healthier life beyond the mid-century mark. From free radicals to inflammatory immune cells, the molecular details of biological degeneration can be addressed by nutritional products, as evidenced by a continuous flood of research findings.
A degenerative disease is a non-infectious illness marked by progressive deterioration of body tissues and organs due to normal wear and tear, lifestyle and diet. These diseases plague federal lists of prevalent maladies and causes of death among Americans, and they cost the country billions in health care expenses. What’s more, many patients suffer numerous debilitating symptoms and experience a steady decline in quality of life.
Genetic factors are prominent in the development and pathology of degenerative disease, but ongoing poor nutrition can certainly be a catalyst. This has turned the research spotlight on nutritional compounds and how they can help manage the risk, onset and progression of these devastating maladies.
Supplements for Multiple Degenerative Conditions
Perhaps due to their connection to aging and general diet,
numerous degenerative diseases share risk factors and natural solutions, making
some supplements beneficial for the management and prevention of many of these
diseases. For instance, Frederic Vagnini, M.D., director of the Cardiovascular
Wellness Center in Long Island, N.Y., has noticed a crossover between heart and
Alzheimer’s diseases in terms of lifestyle factors and conditions that
increase risk of both diseases. He reported a study sponsored by Kaiser
Permanente and involving 9,000 adults showed known risk factors for
cardiovascular disease (CVD), including smoking, high cholesterol and
hypertension, were also risk factors for dementia. In fact, he has seen a number
of cognitive impairment conditions in his cardiovascular practice. “Hypertension,
stress, elevated cholesterol and obesity all undermine the vascular system in
the heart; it is not surprising that they also negatively affect the same
vascular system which delivers blood to the brain,” Vagnini said. “And it is
logical to conclude those nutrients that relieve heart disease—antioxidants,
fish oils and folic acid —will also be effective against the onset of dementia
and Alzheimer’s.”
Among the beneficial compounds for both CVD and Alzheimer’s are essential fatty acids (EFAs), primarily long-chain omega-3s. Doug Bibus, Ph.D., scientific advisory board member for Coromega, reported purified fish oil has become one of the most popular supplements on the market today. He noted the expanded research and attention prompted the American Heart Association (AHA) to recommend fish oil supplementation to provide 1 g/d of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). The GISSI Prevenzione trial demonstrated heart attack survivors taking 1 g/d of marine EFAs experienced significantly reduced overall deaths from CVD, as well as reduced incidence of stroke and recurring heart attacks.1 Additional clinical research found fish oil containing EPA and DHA has decreased incidence of stroke by as much as 28 percent and incidence of thrombotic infarction by 33 percent.2 Overall, science has shown these marine-source omega-3 fatty acids protect against heart disease via several mechanisms of action, including antiarrhythmic, antithrombotic, antiatherosclerotic and anti-inflammatory activities, lowering blood pressure, lowering triglyceride concentrations and improving endothelial function.3
EFAs from flaxseed are similarly effective against CVD, as flaxseed oil increases both EPA and alpha linolenic acid (ALA) in the body.4 ALA from flax has been shown to decrease endothelial activation and vascular inflammation,5 in addition to reducing levels of C-reactive protein (CRP)—a primary marker of inflammation.6
Omega-3 long-chain EFAs are equally important to brain health, as they provide physical building blocks crucial to the development and maintenance of the structural and functional integrity in the brain, including neuronal cell membrane phospholipids.7 The prominent fatty tissue in the brain is comprised mainly of DHA, and deficiencies or imbalances of EFAs can adversely affect brain health. French scientists discovered the process of aging causes negative changes to the brain’s fatty acid composition of structural phospholipids—particularly DHA—that could possibly impair cognitive function.8 They later found DHA-rich eggs could correct these alterations in the hippocampus region of the brain,9 which is the site of deterioration in Alzheimer’s. An early 2005 study showed chronic administration of DHA increased antioxidant defenses in an animal model of Alzheimer’s disease, suggesting the fatty acid may prevent learning deficiencies associated with the degenerative condition.10
Still further evidence of the benefits of EFAs across a broad range of degenerative diseases has been offered by arthritis researchers, who cite anti-inflammatory actions. Gamma linolenic acid (GLA) appears to manage rheumatoid arthritis (RA) by inhibiting certain pro-inflammatory cells, including interleukin-1 (IL-1) and TNF-alpha.11 Among the many researched sources of GLA, evening primrose oil reduced RA pain and stiffness;12 borage oil reduced prostaglandins, cytokines and various oxygenation products associated with inflammatory arthritis;13 and black currant oil, which contains both GLA and ALA, suppressed inflammation and joint tissue injury.14
As for fish oil EFAs in bone and joint management, studies have shown marine fats can control anti-inflammatory prostaglandins, cytokines, chemokines and degradative enzymes in RA patients,15,16 in addition to affecting intracellular signaling pathways, transcription factor activity and gene expression.17,18 These mechanisms of action underlie fish oil’s beneficial effect on arthritis symptoms, including tender and swollen joints, morning stiffness, joint pain, fatigue and grip strength.19
Beyond the impact on inflammatory cells, omega-3s can benefit bone health by preserving bone mineral density (BMD), a factor in degenerative bone disease, or osteoporosis. A 2005 University of California, San Diego, study confirmed an inverse relationship between BMD and the ratio between omega-3 and -6 fats.20 They concluded a more balanced intake of omega- 3 and -6 fats could help preserve skeletal integrity in old age. EFAs have also been found to inhibit osteoclast generation and activation,21 while positive bone mineral conservation was correlated to high intake of omega-3s and isoflavones.22
Isoflavone-rich soy can not only help improve BMD23 by stimulating bone formation and suppressing bone resorption,24 but it is also useful in other degenerative diseases, such as CVD and cancer. AHA recommended soy protein for cholesterol management, and the Food and Drug Administration (FDA) authorized a health claim involving the intake of 25 g/d of soy protein for reduced risk of heart disease, as consumption of soy has been linked to improved plasma lipid profile and vascular activity, as well as reduced LDL oxidation.25
While isolated soy protein has improved the HDL-to-LDL ratio in diabetics26 and lowered LDL cholesterol in heart patients,27 there is some debate about whether the benefits of soy on heart health are due to the protein or the isoflavones. A meta-analysis of heart studies involving high and low isoflavone levels and soy protein intake revealed high isoflavone levels more drastically lowered LDL cholesterol.28 Further study has shown higher intake of isoflavones can also lower triglycerides and reduce CVD risk factors.29 On the other hand, a recent controlled trial conducted in three Chinese communities found soy protein lowered both diastolic and systolic blood pressure,30 which lead to theories that soy protein could be useful in preventing and treating hypertension.
Soy protein and isoflavones have also proven useful in lowering the risk of numerous cancers, including prostate,31 colorectal32 and breast carcinomas.33 In particular, a soy protein diet can increase apoptosis in prostate cancer cells,34 while soy isoflavones genistein and daidzein can hinder prostate carcinoma growth and tumor development.35 A recent meta-analysis performed by Washington University, St. Louis, and the Solae Co., involving studies from the United States, Canada and Asia, revealed a 30-percent reduction in risk of prostate cancer among men who regularly consumed foods containing soy protein.36
Clinical trials have also found soy can lower PSA (prostate-specific antigen), a marker of the disease. In colorectal cancer, soy reduced colonic abnormalities that can lead to cancer development,37 while genistein has promoted apoptosis in colon cancer cells.38 Genistein similarly inhibited tumor growth in the MCF-7 breast cancer model,39 and generated a 40-percent reduction in tumors in the F3II breast cancer model.40 In additional study, genistein functioned comparatively to the drug Tamoxifen in inducing both apoptosis and reducing cancer cell proliferation.41 However, the isoflavone has been found to promote certain breast cancers in women under certain circumstances,42 so it is especially important for consumers to keep their physicians informed of genistein supplementation.
One of the triggers of the degenerative process of cancer and other diseases is damage to DNA and other crucial organ, vascular and skeletal cells by free radicals. Thus, certain antioxidants are common primary nutritional tools in cancer in heart disease management, and are being investigated for similar roles in osteoporosis, arthritis, dementia and diabetes. Antioxidant vitamins and minerals factor in most degenerative diseases. Plasma antioxidant levels have been shown as important factors in arthritis,43 osteoporosis,44 CVD,45 diabetes46 and cancer.47 Their primary role in cancer is to support the immune system’s resistance of cancer development, although they have also demonstrated specific beneficial activities in certain cancers.
Vitamin C may prevent lung48 and bladder,49 cancers but it contributes more broadly to cancer management by promoting antibodies and interferon, which is important in attacking tumors.50 This antioxidant has shown promise in improving BMD in osteoporosis,51 and may prevent bone destruction while supporting normal bone structure.52 In arthritis, vitamin C is extolled for its well known role in collagen production, as type II collagen is present in articular cartilage. Scientists have further indicated vitamin C promotes synthesis of aggrecan, an aggregating chondroitin sulfate proteoglycan that comprises 10 percent of cartilage weight.53 Cognitive performance and dementia are also impacted by vitamin C levels, which appear to be protective against degenerative decline.54,55
Vitamin E might have suffered some bad media-driven attention recently, but its benefit to CVD, Alzheimer’s, cancer and diabetes has been well documented. While vitamin E was recently found to increase, but not decrease, CVD mortality in one study,56 the recent Women’s Health Study found 600 IU taken every other day did not increase mortality but led to a decrease in CVD deaths in healthy women.57 On protection against CVD development, two additional studies showed alpha-tocopherol can protect against LDL oxidation.58,59 Vitamin E has also improved cardiovascular parameters of diabetes,60 and the National Health and Human Nutrition Examination Survey (NHANES) revealed subjects with metabolic syndrome had low plasma levels of the vitamin.61
In brain health, vitamin E can counteract cognitive decline and protect against neuronal damage. Data from the Chicago Health and Aging Project showed high vitamin E intake reduced cognitive aging by eight to nine years.62 And based on antioxidant measurements in cerebrospinal fluid, vitamin E may also delay development of Alzheimer’s63 and Parkinson’s diseases.64 More recently, researchers from the Harvard School of Public Health investigating the role of oxidation in brain disease reported vitamin E can decrease risk of mortality from myotrophic lateral sclerosis (ALS), a neurodegenerative disease also known as Lou Gehrig’s disease.
In cancer, vitamin E shields the immune system from oxidative stress, specifically defending white blood cells and the thymus gland, which regulates T-cell proliferation.65 On specific cancer sites, increased blood levels of vitamin E during the early development of lung cancer can limit the progression of the disease.66 And dietary intake and plasma levels were shown as important to development of liver,67 cervical,68 breast69 and prostate70 cancers.
Vitamin A is also effective against cancer and heart disease, although its role in bone and joint degeneration is mixed—excess levels might promote hip fractures by promoting bone resorption,71 while deficiency is common in arthritis patients.72 Its positive effect on cancer is partially due to its supporting the production of white blood cells, including T-helper cells.73 In fact, derivatives of vitamin A have successfully inhibited lung cancer cell growth while promoting cancer cell death.74 In colon cancer, the vitamin A pre-cursor betacarotene has inhibited tumor growth and increased cancer cell apoptosis.75 In vitro study has shown natural killer (NK) cells treated with beta-carotene exhibited increased anti-tumor activity.76 Most recently, beta-carotene has been investigated for cardioprotection, as Harvard researchers reported dietary intake of beta-carotene decreases risk of heart attack.77
Fellow carotenoids lycopene and astaxanthin have also garnered a wide range of degenerative disease research attention, as carotenoids protect cells and tissue from oxidation. In fact, the most recent study on carotenoids showed blood levels of alphacarotene, beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin and lycopene are inversely related to risk of type II diabetes.78 Also, low concentrations of carotenoids—including astaxanthin, alpha-carotene, lycopene, zeaxanthin and beta-cryptoxanthin—were discovered in numerous colon cancer cases.79
More specifically, astaxanthin has demonstrated an ability to improve antitumor immune response,80 while lycopene, primarily from tomatoes, excels at quelling singlet oxygen and protecting tissue in many prime cancer locations—liver, lungs, breasts and prostate.81
Higher intake of lycopene-rich vegetables such as tomatoes can also affect the scope of human papillomavirus (HPV) infection, which can lead to cancer development.82 And, liver cancer was suppressed in high-risk patients given 10 mg lycopene, 10 mg of carotenoids and 50 mg of alpha-tocopherol (as Lyc-OMato ®, from LycoRed).83 Plasma levels of lycopene are similarly important to breast cancer risk,84 and the carotenoid has inhibited the MCF-7 breast cancer cell line.85 However, lycopene might be most beneficial in prostate cancer, as the carotenoid has lowered PSA and other prostate cancer markers by as much as 17.5 percent,86 and has also helped decrease tumor size.87
In CVD, lycopene works as an antioxidant, in addition to impacting LDL degradation and particle size, as well as altering endothelial function.88 Researchers reviewing Kuopio Ischaemic Heart Disease Risk Factor Study data associated low serum lycopene levels with significantly increased risk of acute coronary events or stroke, as well as significantly higher IMT (intima-media thickness) of the carotid artery.89
For its part in degenerative disease, astaxanthin (as AstaREAL®, from Fuji Health Science) has recently exerted beneficial antioxidant protection against hypertension, stroke and vascular dementia in a Japanese trial.90 This colorful carotenoid has also proven useful in arthritis as both an antioxidant and anti-inflammatory supplement ingredient. Scientists found it inhibits nitric oxide production and suppresses gene expression associated with inflammatory diseases, such as rheumatoid arthritis (RA). Its anti-inflammatory effects were highlighted in another trial, as astaxanthin (as BioAstin®, from Cyanotech) improved pain and mobility scores in RA patients after four and eight weeks of supplementation.91
Besides carotenoids and isoflavones, there are numerous other phytochemicals in fruits, vegetables and plants that help tame all kinds of degenerative diseases. Like soy and fish, tea is a popular medicinal dietary staple, and scientists have increasingly focused on the antioxidant benefits of tea catechins in most major degenerative diseases. Green and black tea catechins can scavenge free radicals before cell damage occurs.92 Green tea has been linked to reduced risk of breast cancer,93 but study findings on other cancers have uncovered more detailed actions. Tea’s epigallocatechin gallate (EGCG) can cause prostate cell cancer death by inducing expression of the gene clusterin,94 while EGCG and its sibling ECG promote apoptosis in and inhibit growth of cervical cancer cells.95 In liver cancer studies, catechins from green and black teas have been equally effective in reducing the size of chemically induced tumors in mice.96 These flavonoids are no less aggressive against heart disease, as researchers have reported tea catechins work as direct and indirect antioxidants, increasing resistance to lipid peroxidation and decreasing atherogenesis.97 On its own, EGCG has decreased cytokines responsible for the destruction of pancreatic beta-cells in diabetes study,98 while black tea intake improved BMD and was inversely related to bone concentrations of vital calcium and phosphate in a Presidency University, Calcutta, study.99 Tea antioxidants have similarly shown great promise in neurodegenerative diseases, as Japanese researchers found tea catechins can prevent DNA damage in brain cells.100 Specifically, EGCG from green tea prevented oxidative damage in a Korean in vitro study, increasing the survival of hippocampus cells exposed to amyloid protein—a factor in Alzheimer’s—in addition to decreasing reactive oxygen species (ROS).101
Free radicals are especially damaging to the brain, according to Barry Halliwell, M.D., renowned neurodegenerative disease researcher and director of the NUS Graduate School for Integrative Sciences and Engineering, Singapore. “The brain is very prone to free radical attack, the damage from which is elevated in all the major neurodegenerative disease,” he said. “Sadly, most dietary antioxidants do not cross the blood brain barrier, so a good diet is needed over many years to raise brain antioxidant levels.”
A University of Western Australia, Perth, study revealed combination antioxidant therapy in an animal model resulted in increased life span and a marked reduction in inclusion body formation in the hippocampus.102 According to the researchers, antioxidant therapy might be therapeutically effective against neurodegenerative diseases. Among the antioxidants in this study were vitamin C and French maritime pine bark extract (as Pycnogenol®, from Horphag). Earlier study showed Pycnogenol could reduce vascular damage caused by beta-amyloid protein, one of the hallmarks of Alzheimer’s disease.103 This vascular protection is the prominent action of Pycnogenol, which has been beneficial to other degenerative diseases involving vascular factors.
Pycnogenol can improve endothelial function in mildly hypertensive patients,104 in addition to protecting against oxidative stress, inhibiting platelet aggregation and reducing LDL cholesterol levels.105,106 The antioxidant also improves endothelial function and lowers blood glucose levels in people with type II diabetes,107 and can augment capillary resistance and retinal leakage in diabetic retinopathy cases.108 Researchers from Loma Linda University, California, reported Pycnogenol can inhibit expression vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), making the supplement useful in atherosclerosis, diabetes and cancer metastasis.109 Additional study by these same researchers showed Pycnogenol selectively induces death in human mammary cancer cells (MCF-7) without affecting normal human mammary cells.110
Fellow antioxidant coenzyme Q10 (CoQ10) may be most important in degenerative diseases for its role in the mitochondria, where it helps maintain cellular energy. CoQ10 has been well researched in heart health. It has demonstrated favorable activity on patients with heart disease, including increasing cardiac output and reducing stroke volume,111 as well as reducing hypertension.112 Additional studies have found combined supplementation of CoQ10 with vitamin E reduced atherosclerosis progression and increased plasma resistance to lipid peroxidation.113 The coenzyme is also an effective counteractive tool for patients using statin drugs. According to research, use of statins for as few as 30 days can significantly decrease blood concentrations of CoQ10.114
People with diabetes often experience cardiovascular complications, suggesting CoQ10 could be effective in managing diabetes. In fact, research has discovered CoQ10 supplementation can reduce systolic and diastolic blood pressure in Type II diabetics with dyslipidema.115 University of Western Australia, Perth, scientists noted CoQ10’s ability to improve endothelial function in diabetes might be due to the supplement’s antioxidant actions.116 They explained increase oxidative stress in diabetes contributes to the development of endothelial cell, which CoQ10 improves by recoupling endothelial nitric oxide synthase (eNOS).117 University of Toledo, Ohio, researchers added CoQ10 can protect islet cells—pancreatic cells that produce and secrete insulin—from oxidative damage caused by free radicals.118
Antioxidant activity is also indicated in research on CoQ10 and cancer. Deficiencies of the coenzyme have been found in cancer patients, especially in those with cervical cancer,119 and researchers suggested the supplement might limit the toxicity of cancer treatments.120 However, CoQ10’s impact on prostate cancer was more explicitly defined by researchers from the University of Granada, Spain, who showed CoQ10 supplementation significantly lowered cell growth of the pC3 cancer line without affecting normal cells.121
Reduced mitochondrial levels of CoQ10 have also been found in Parkinson’s disease patients.122 Degeneration of dopaminergic neurons progresses this neurological disease, while mitochondrial dysfunction and oxidative damage play a key role in both Parkinson’s and Alzheimer’s.123 Pretreatment with CoQ10 significantly reduced neuronal death in a Parkinson’s cell study,124 while Austrian research revealed the preserving potential of antioxidant and bioenergetic CoQ10 against various models of oxidative stress in Parkinson’s.125
It makes sense that certain antioxidants would be so effective in numerous degenerative diseases, but similar wideranging benefits have been associated with non-antioxidant B vitamins. A recent study concluded cognitive disease depletes vitamin B12 and folate levels,126 while previous study found mental decline is marked by reduced levels of B6, B12 and folate.127 Folate has further demonstrated the potential to help prevent brain degeneration in Alzheimer’s disease.128 University of California, Los Angeles, researchers concluded folate intake at above the recommended dietary allowance (RDA) of 400 mcg/d could lower the risk of Alzheimer’s by as much as 55 percent.129 In other neurodegenerative study, vitamin B1 inhibited neurotoxicity and degeneration of the cerebellum, especially in cases of high dietary alcohol intake. In bone and joint research, adequate vitamins B6 and B2 were associated decreased incidence of osteoarthritis,130 and folate and B12 intake reduced hip fractures following stroke.131
Folate and B12 have also been indicated in prevention of various gastrointestinal cancers, especially colon cancer.132 Adequate intake of folate, B12, B2 and B1 were also linked to reduced risk of cervical cancer.133 Meanwhile, vitamin B6 supplementation can not only decrease the risk of colon cancer,134 but it also impedes tumor growth and cancer metastasis.135
The effects of B vitamins on heart disease are more defined. Folic acid can reduce high homocysteine levels associated with venous dysfunction and increased risk of CVD. Accordingly, low levels of folate can double the risk of heart attack,136 while high folate intake can reduce the risks of both peripheral artery disease137 and ischemic stroke.138 A recent Harvard study found younger women taking 1,000 mcg/d of folate from both food and supplements experienced a 45-percent reduced risk of hypertension.139 Fellow B vitamin niacin is well studied for its ability to increase beneficial HDL cholesterol,140 which led to investigations of combining the vitamin with statin therapy to reduce carotid IMT.141 One study found niacin taken in conjunction with lovastatin not only increased HDL, but lowered LDL and triglyceride levels.142
Also from the vitamin B family, biotin appears to work effectively against diabetes. “Biotin and R+ alpha lipoic acid work on the degenerative disease cellular level, via different pathways, to increase glucose uptake, improve insulin sensitivity and mediate insulin signaling,” said Laurence Berube, president of Glucorell, Inc. “Together these balanced nutrients have a superior impact on glucose metabolism to those of popular drugs.”
Disease-Specific Supplementation
There is a healthy list of nutritional ingredients well-researched for one or two specific degenerative diseases; however, this focus does not render these supplements any less effective than their multi-disease counterparts. Rather, these disease-specific nutrients have very distinct mechanisms of action that have proven powerful against particular degenerative activities. Following are a select few of those compounds. (For more in-depth review, check out www.hsrmagazine.com for our disease-specific in-depth feature articles.)
“Our most recent research showed that BioCell Collagen II actually inhibits hyaluronidase, which is the enzyme that breaks down hyaluronic acid,” said Asma Ishaq, vice president of marketing for Biocell Technology. “It addresses aging concerns, whether they are joint or skin health, from both a reparative and preventative perspective.” Glucosamine is one of the most popular supplements among arthritis patients, as it inhibits joint space narrowing173 and slows progression of arthritis, improving symptoms such as pain and stiffness.174 Chondroitin sulfate is the most prevalent GAG in cartilage and, as a supplement, can limit progression and symptoms of arthritis, including inhibiting joint space narrowing, reducing pain and improving overall mobility.175 In the synovium, HA injections have proven effective in managing pain and stiffness by reducing inflammatory cells in synovial fluid,176 but research on oral HA is still in early stages.
Dietary supplements have made substantial progress against degenerative diseases and related conditions. While each such disease can be managed with the help of numerous disease-specific compounds, it is important to note a few supplements can address a broad spectrum of degenerative diseases, which can share factors such as vascular problems. “Hypertension, stress, elevated cholesterol, and obesity all undermine the vascular system in the heart, but it is not surprising that they also negatively affect that same vascular system, which delivers blood to the brain,” Vagnini said. “It is logical to conclude that those nutrients that relieve heart disease—antioxidant, fish oils, folic acid—will also be effective against the onset of dementia and Alzheimer’s.”
Thus, consumers, in general, could benefit from the preventive and protective actions of EFAs, soy and certain antioxidants, while consumers who already have or are at a high risk for a particular disease can choose from an even longer list of targeted supplements.
For a complete list of references to this story, visit
www.hsrmagazine.com
after December 1st, or e-mail hgranato@vpico.com.
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