Nutritional Fundamentals for Health

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Role of Natural Antioxidant Nutrients in the Prevention of Human Diseases Other than Cancer and Cardiovascular Diseases

1. Introduction: 
There is compelling evidence to suggest an important role of oxidative stress in human diseases. Strategies to mitigate the damaging effect of oxidative stress include the use of antioxidants in the prevention and management of human health disorders. Extensive research over the past several decades focused on the protective effect of antioxidants and in particular vitamins such as A, C and E. Most of the initial research was directed towards the two major human diseases, cancer and cardiovascular diseases (CVD). Recent research is providing evidence to indicate the role of natural antioxidant phytonutrients (NAP) such as carotenoids and polyphenols in the prevention of human diseases other than cancer and cardiovascular diseases as shown in Table 1 
               Table 1. Role of natural phytochemical antioxidants in human diseases other than cancer and CVD 

Bone diseases -Osteoporosis
Respiratory diseases
Male infertility
Ultraviolet induced sunburns and other skin diseases
Neurodegenerative and Mental disorders
Inflammatory disorders - Rheumatoid arthritis
Ocular diseases
Oral disorders
This article summarises the most recent information pertaining to the role of NAP in these other equally important diseases.
2. Hypotheses underlying the role of oxidative stress and antioxidants in human diseases 
The role of oxidative stress in human diseases is based on the hypothesis that oxidative stress is caused by several environmental and life style factors including diet and smoking leading to the accumulation of reactive oxygen species (ROS) and other free radicals that are responsible for cellular damage and the causation and progression of human diseases. Antioxidants by virtue of their ability to react with the free radical mitigate their damaging effect and thereby reduce the risk of chronic diseases. 
3. Osteoporosis
Osteoporosis is a metabolic bone disease characterized by gradual bone loss over many years. The two major bone cells, the bone forming osteoblasts and the bone resorbing osteoclasts, are involved in the process of bone remodeling. Metabolic bone diseases such as osteoporosis result from the disturbances in the remodeling process. Oxidative stress and antioxidants can influence this remodeling process at many sites in the process. In vitro and clinical studies in our laboratory as well as others have shown a relationship between oxidative stress and the development of osteoporosis. Based on the results from our tissue culture studies using clonal human osteoblast and rat marrow osteoclast cells, we undertook clinical studies to determine whether phytonutrients including carotenoid lycopene and the polyphenol-containing nutritional supplement will prevent the development of osteoporosis in postmenopausal women.-. In both clinical studies, we showed that the development of osteoporosis may be prevented with the consumption of lycopene and polyphenol-containing supplements in postmenopausal osteoporosis. Our results demonstrated that daily consumption of either lycopene or polyphenols either in the form of tomato juice or nutritional supplement may mitigate the damaging effect caused by oxidative stress thereby reducing the risk of osteoporosis. However more studies are needed in the future to confirm our findings and to delineate the mechanisms of action of NAP.
4. Respiratory diseases
Asthma, a lung disease caused by inflammation is probably the most studied respiratory disorder. Symptoms of asthma include shortness of breath, wheezing, chest tightness and coughing. Both children and adults are susceptible to asthma worldwide. Lifestyle activities such as diet and smoking which influence oxidative stress play an important role in the incidence of asthma. There is evidence of an oxidant-antioxidant imbalance in asthma. Antioxidant-rich diets and supplements are therefore associated with reduced asthma prevalence in epidemiologic studies. Although most of the reported clinical studies have shown improvement in the incidence and severity of respiratory disorders, there are some studies which showed no effect.
5. Hypertension 
High blood pressure, also known as hypertension is a condition commonly associated with narrowing of the arteries. It is the single most important risk factor for heart attacks and stroke. High blood pressure puts strain on arteries leading to heart attacks and strokes. A causal relationship between oxidative stress and hypertension is based on the observations that subjects with high blood pressure also have high ROS and oxidative stress. Follow up human supplementation studies have shown that lycopene, a natural antioxidant present in tomatoes and nutritional supplements was effective in reducing systolic blood pressure significantly. In a recent meta-analysis of lycopene intervention studies on blood pressure, it has been shown that high dosage of lycopene supplementation (>12 mg/day) could lower systolic blood pressure more significantly compared to control, especially for participants with baseline systolic blood pressure of >120 mmHg.. Although, both epidemiological and clinical studies have shown that intake of 12 mg per day of lycopene can have protective effect against systolic blood pressure, only a few controlled human clinical trials have been reported in the literature
6. Male infertility 
Male infertility is a reproductive disorder affecting 7-10% of adult male in their reproductive years. Among several factors that contribute to male infertility, oxidative stress is considered to be important since one of the main component of spermatozoa membrane are the polyunsaturated fatty acids that are prone to oxidation damage resulting in reduced sperm motility and viability. Semen of infertile men contains significant levels of ROS compared to fertile men, supporting the cause-effect relationship between oxidative stress and male infertility. Several initial animal and human intervention studies with antioxidants such as vitamins C and E, glutathione and l-carnitine showed improvement in sperm quality and functionality. More recent studies with NAP and in particular lycopene have also shown their beneficial effect in improving the functionality of sperm from infertile men. Based on a review of multiple studies, it was suggested that consuming 4-8 mg of lycopene daily for 3- 12 months was sufficient to improve male infertility. 
7. Skin, mental, inflammatory, ocular and oral diseases 
Attention is now being given to the role of antioxidant phytochemicals in these other important human diseases. Of these diseases, ultraviolet induced sunburns and other skin diseases and neurodegenerative and Mental disorders have been given more attention. Information related to the other disorders, based on in vitro and animal studies, is still in its infancy. Initial results demonstrate positive beneficial effect of antioxidants. Although more clinical intervention studies using well defined study participants and physiologically relevant dose levels over longer periods are required, it is reasonable to assume that oxidative stress may be an important causative factor and therefore antioxidants may be beneficial in lowering the damage caused by oxidative stress and may play a role in the prevention and management of these diseases. 
8. Conclusion 
Available data to date suggests that consumption of antioxidants including dietary and supplemental sources such as lycopene and polyphenols may be beneficial in the prevention and management of several if not all human diseases. However, more studies are required in the future where attention is given to details of study protocols that include fully randomised and double blind procedures as well as well defined patients, proper controls, larger size of subjects, longer periods of intervention, use of physiologically relevant dose levels and the measurement of end points that are associated with antioxidant properties and the disease. Only then can we make definitive conclusions and provide effective recommendation as to the use of natural antioxidants in the prevention, management and perhaps the treatment of human diseases.
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  2. Bronwyn S. Berthon BS and LG. Wood 2015, Nutrition and Respiratory Health—Feature Review. Nutrients: 7:1618–1643. 
  3. Evans JA and EJ Johnson. 2010. The Role of Phytonutrients in Skin Health. Nutrients: 2: 903–928. 
  4. Griffiths K1 et al 2016. Food Antioxidants and Their Anti-Inflammatory Properties: A Potential Role in Cardiovascular Diseases and Cancer Prevention. Diseases 4:28-49. 
  5. National Institute of Health, National Cancer Institute 2017 Antioxidants and Cancer Prevention. Web link:
  6. Rao A., M. Ray, and L. Rao. 2006. Lycopene. In: Advances in Food and Nutrition Research. ed by: Taylor SL, Academic Press Publication, New York, p 99-164. p. 99-164. 
  7. Rao A, and L. G. Rao. 2007. Carotenoids and human health (Review) Pharmacological Research. 55:207-16. 
  8. Rao LG, N. Kang, AV Rao. 2012. Polyphenol antioxidants and bone health: A review.. pp. 467-486.In: Phytochemicals: A global perspective of their role in nutrition and health. Ed. AV Rao. Inyech Publishing, Croatia 
  9. Rao, LG and AV Rao. 2015. Oxidative stress and antioxidants in the risk of osteoporosis – Role of phytochemical antioxidants lycopene and polyphenol-containing nutritional supplements. Pp. 247-260. In: Phytochemicals – isolation, characterisation and role in Human Health. Eds. AV Rao, and LG Rao. Intech Publishing. Croatia 
  10. Rao LG and AV Rao. Lycopene and bone health. In: Lycopene and Tomatoes in human mutrition and health. Eds: AV Rao, G. Young, LG Rao. Francis and Talylor Group Publisjing. Florida, USA.