October 18, 2013

Virender Sodhi, MD(Ayurved), ND

The term circadian rhythm refers to the synchronization of the biological/physiological clock of the individual to the natural rhythms of one’s environment. This synchronization is orchestrated by a central clock and several peripheral clocks. While the central clock found in the Suprachiasmatic nucleus (SCN) in the central nervous system, peripheral clocks are located in various peripheral organs like liver, kidney, heart, GI tract, skin, adrenal, thyroid, sexual glands, etc.

The SCN manages the cycling gene expression of various hormones and other signaling molecules based on the day-light cycle of the local environment. This cycling of signals manages the expression of signals and functioning of the peripheral clocks in various organs. Recent studies have shown that these peripheral clocks can also be controlled by timing of meals eaten by an individual in a day. In fact, the peripheral organs adjust their clocks on a daily basis, within hours of a change in meal times or meals size. (1) The dual control of the peripheral clocks may be a result inconsistent meal availability that was a normal part of our primitive past. Therefore, the question arises, whether central control or meal control of the peripheral clocks healthier for the individual?

A pair of recent studies have looked at the effect of meal times on health of diabetic individuals. A variety of measurements and indices are used to measure the disease progress among diabetes. These experiments measured Glycosylated Hemoglobin (HbA1c), Body mass index (BMI), appetite and satiety to assess effect of breakfast on disease control.

In the first study, studied individuals were divided into two diabetic groups, 1) Early Chronotypes, those who sleep earlier at night and wake earlier in the morning, and 2) Later Chronotypes, those who sleep later at night and wake later in the morning. Here, the researchers found that Later Chronotypes were more likely to skip breakfast on waking and have lunch as the first meal; while, Early Chronotypes woke earlier and often had a good breakfast at the start of their day. It is suspected the breakfast skipping may be due missing of natural central activation of hunger that occurs with cyclic cortisol rise in the morning. Among the health outcomes, this study found that skipping breakfast was associated with higher HbA1c and higher BMI – both indicating to elevated risk of diabetic complications and heart disease. (2)

The second study from scientists in Israel looked at breakfast size and its effects on the health of diabetics. Among 59 individuals studied, half were placed in a small breakfast group, and half were in large breakfast group. The large breakfast consisted of up to 33% of the calories eaten in a day, compared to 12.5% of total daily calories obtained from small breakfast. Also, the large breakfast group ate more protein and fat, as well as relatively less carbohydrate content than small breakfast group. Over the course of the 13 week study, it was found that large breakfast group had three-fold better blood glucose control and four-fold better blood pressure control. Also, large breakfast group reported less hunger later in the day. Additionally, about 1/3 of those in large breakfast group were able to reduce diabetes medication, while 17% of those in the small breakfast group had to increase medication for blood sugar control. (3)

In conclusion, it can be said that it is important to respect the central circadian rhythm of the body, in order to allow normal cycling of hormones, nutrition, and functioning of the organs through the body. This seems to generate the best health outcomes including lower BMI, lower blood glucose, reduced appetite and increased satiety in all individuals (4), especially those who have diabetes.

Jog to your Health

It is common knowledge that staying physically active keeps one fit and healthy. This notion is supported by overwhelming evidence that shows lowered risk of diseases as a result of regular exercise. For example, regular exercise not only reduces occurrence of cardiovascular disease (CVD) but also prevents death due to CVD, (5). Incidence of colon cancer risk is reduced by 20-30%, breast cancer risk reduced by 25%, while lung and prostate cancer occurrence may both be reduced up to 30%, (6). Exercise also improves blood sugar control, reduces BMI, and prevents one from developing insulin resistance that can lead to diabetes overtime, (7). Mood disorders like depression and anxiety can also be curbed by regular exercise.

A 2011 review of multiple studies done over the years explained the effect of physical activity on the aging nervous system. The authors concluded that all evidence points towards the fact that exercise through adulthood can improve blood flow and oxygenation to the brain, thus slowing down process of oxidative degeneration of nervous system. Additionally, exercise can have beneficial physiological and cognitive effects on the brain by modifying profile of gene-expression in the individuals who exercise regularly. This practice overtimes slows down or even stops development of diseases like age-related dementia and Alzheimer’s disease. (8)

With all these benefits, why are so few people still exercising?

Often taking the time to exercise proves to be a challenge. Sometime one may feel overwhelmed by the fitness culture that focuses on looks rather than balanced health. Others may find that they know little about what kind of exercise can most efficiently benefit their health. In these cases, one may exercise too intensely and injure the body or one may not exercise vigorously enough to stimulate the benefits of exercise. Finally, there is the question of how much exercise does one need to do anyway?

Reflecting on years of study, there have been hundreds of observations that confirm that moderate intensity exercise done regularly over a lifetime or at any period in life relates to reduced incidence of multitudes of diseases including heart disease, vascular disease, diabetes, neurodegenerative disease, breast, colon and lung cancer, etc. Generally, these studies describe that moderate exercise may range from brisk walking at the rate of 3-5 mph, light jogging, riding a bicycle up to 10-20 mph, water aerobics, etc. While playing tennis, squash, running, swimming, bicycling over 20mph, etc. are deemed to be vigorous forms of exercise.

General guidelines offered by the Center for Disease Control recommend best outcome from regular exercise is derived when one can perform 150 minutes of moderate intensity exercise, with 2 days of weight training for all muscle groups, or 75 minutes of vigorous exercise, with 2 days of weight training for all muscle groups. Best results are attained when one can divide up the time of exercise in to small bits. An example under CDC recommendations explains, 10 minutes of brisk walking 3 times/day for 5 days/week, adds up to 150 minutes of moderate intensity exercise, (9). Dividing up exercise regimen in this way prevents over-working joints, ligaments, muscles and tendons, thus reducing chance of injury. This regimen also exercises body’s capacity to mobilize and eliminate toxins, as well as the capacity to repair itself.

This ‘simple and free’ form of self-care may significantly reduce your cost of health care, while improving your mood, energy, digestion, and vitality. Additionally, Individualized exercise recommendations are more likely to translate into action, therefore a consultation with your naturopathic doctor or physical trainer is recommended as you embark on an exercise program.

Therapeutic Activity of Amla through Modifying of Gene Expression

Amla

Phyllanthus emblica, commonly known as Amla or Indian Gooseberry, is an extensively used in Ayurveda for its nutritional and medicinal values. The fruit of this shrub is described as a rasayana, an adaptogenic-rejuvenator with anti-inflammatory, anti-oxidant, and fever-reducing capacities. It is also considered one of the richest sources of Vitamin C, with one fruit containing as much of the vitamin as three oranges. Research into the actions of this herb allows one to appreciate the novel capacity of herbs to promote healing by modifying gene expression, an action that no drug therapy has proven capable of. Here, we shall look at three example of such therapeutic activity.

Anti-cancer activity against cervical cancer cells:

Cervical cancer is the third most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths in females worldwide. A large portion of these cancers are associated with infection of cervical cancer cells with Human papilloma virus (HPV). Among the most tumor-causing strains of HPV, about 90% of cancers are related to HPV-16 and HPV-18. Experimenters in this study, observed the therapeutic effect of Amla of cervical cancer cells affected by these strains of HPV.

Action of Amla seems to be two-fold, affect the gene expression in the cells and in the virus. In the cervical cancer cell, extracted molecules from Amla block the formation of the AP-1 (activator protein-1) that is necessary for the survival of cancer cell. This is accomplished by binding to the DNA of the cell, thus blocking gene expression. This AP-1 protein promotes illness of the cervical cancer cells by supporting proliferation of HPV in cells. Blocking AP-1 tends to blocks gene expression in the form of mRNA transcription, thereby keeping HPV from growing. Since, HPV transcription is necessary for survival of cervical cancer cells, blocking it stunts the growth of the cancer cells (10).

Slowing down Progression of Rheumatoid Arthritis and Osteoporosis

Osteoclasts are a class of cells that are involved in breaking down bone as a normal part of bone metabolism. Normally, while osteoclasts break-down bone tissue, osteoblasts build and remodel this same tissue thus constantly rejuvenating the skeletal system. As we age, activity of osteoblasts becomes slows down due to hormonal changes, thus overt activity of osteoclast resulting in problem with balanced bone metabolism. This leads to occurrence of numerous bone pathologies including rheumatoid arthritis and osteoporosis.

In this study, researchers observed the activity of Amla extracts. They found that an extract of Amla interferes with the activity of a gene transcription factor called NFκB, which is involved in osteoclast biology. Extract from the fruit seems to competitively bind the same DNA sites as the NFκB, thus blocking normal gene expression. This leads to death of the osteoclast, and may slow down progress of the degenerative changes (11).

Demonstrating Amla’s Activity as a Rasayana

A rasayana is described as tissue rejuvenative herb that enhances the physiological conditions by either promoting a particular function or suppressing it as needed to create a healthy balance. In this interesting experiment, normal and oxidation-damaged pancreatic beta-cells were exposed to Amla extract. The intention of the experiment was to observe the benefit or damage that may be done the healthy or diseased cell by such exposure. The effect was measured by assessing accumulation of oxidants (lipid peroxidation) and occurrence of cell death (apoptosis).

The interesting part was that when exposed to healthy cells in ideal conditions, effect of Amla was to increase oxidation thus incurring oxidative stress among cells and subsequently blocking the gene expression and cell cycle of the beta-cells, promoting cell death. For the opposite experiment, streptozocin (STZ)-induced cells, which had already increased oxidation and cell damage, were exposed to Amla extract. In these cells, Amla promoted anti-oxidant activity and reduced cellular damage to improve cell survival and overall cellular health (12).

Experimenters attribute this, seemingly, contradictory effects of Amla extract to rasayana action of the herb that creates balance rather than pushing the system in one direction or other. This experiment demonstrates the dynamic capacity of the herb to adapt its action to match the healing that needs to occur.

In conclusion

The list of therapeutic uses of Amla continues to grow as more of its applications are tested and more of its activity is understood. The experiments discussed above do not capture the breadth of this herbs application, rather they highlight beauty and dynamism of herbal medicine in their activity that is rarely matched or imitated by any pharmaceutical drugs.

References:

  1. Oren, Froy. Review: The relationship between nutrition and circadian rhythms in mammals; Frontiers of Neurobiology, Vol. 28, 2007, 61-71.
  2. 2Reutrakul, Sirimon, et. al. The Relationship Between Breakfast Skipping, Chronotype, and Glycemic Control in Type 2 Diabetes; Chronobiology International, Early Online; Informa Health Inc., USA, 2013.
  3. Thompson, Dennis. Big Breakfast May Be Best for Diabetes Patients: Study found morning meal rich in protein, fat actually curbed hunger, helped control blood sugar levels;Health Day; Oct. 10, 2013.
  4. Pereira, MA, et. al. Breakfast Frequency and Quality May Affect Glycemia and Appetite in Adults and Children; The Journal of Nutrition, Dec. 1, 2010.
  5. Shortreed, SM, et. al. Estimating the effects of long-term physical activity on cardiovascular disease and mortality: evidence from the Framingham Heart Study; Heart, 2013; Vol. 99; 649–654.
  6. Friedenreich, Christine, et. al.; State of the epidemiological evidence on physical activity and cancer prevention; European Journal of cancer; 2010; Vol. 4 6, 2 5 9 3 –2 6 0 4
  7. Sanz, C., et. al. Review: Physical exercise for the prevention and treatment of type 2 diabetes; Diabetes & Metabolism 36 (2010) 346–351.
  8. Kaliman, Perla; et. al.; Review: Neurophysiological and epigenetic effects of physical exercise on the aging process; Aging Research Reviews, 2011; Vol. 10, 475-486
  9. Center for Disease Control and Prevention; Physical Activity for Everyone: How much physical activity do adults need?;, Dec. 1, 2011.
  10. Mahata, Sutapa, et. al.; Anticancer Activity of Phyllanthus emblica Linn. (Indian Gooseberry): Inhibition of Transcription Factor AP-1 and HPV Gene Expression in Cervical Cancer Cells; Nutrition and Cancer, 2013, Vol. 65(S1), 88-97.
  11. Piva, Roberta, et. al.; Apoptosis of Human Primary Osteoclasts Treated with Molecules Targeting Nuclear Factor-κB; Natural Compounds and Their Role in Apoptotic Cell Signaling Pathways, Annals of the New York Academy of Sciences, 2009; Vol. 1171, 448–456.
  12. Kalekar, SA, et. al.; Do plants mediate their anti-diabetic effects through anti-oxidant and anti-apoptotic actions? an in vitro assay of 3 Indian medicinal plants; BioMed Central, Complementary and Alternative Medicine, 2013, Vol. 13:257.