The FDA just approved Qnexa for the treatment of obesity and obesity related comorbid conditions such as diabetes, cancer and heart disease. Qenexa is the combination of two well-known drugs, phentermine and topiramate. Phentermine is a central norepinephrine releasing drug that has previously (1959) been approved for short-term treatment of obesity. Topiramate is marketed for treatment of migraines and epilepsy. The combination of the drugs is thought to act in an additive or synergistic manner upon the neural and peripheral pathways that control hunger, satiety and energy homeostasis.
The aim of the Conquer Trial was to examine the effect of low dose, controlled – release, phentermine plus topiramate on weight loss and associated comorbid conditions in overweight and obese adults. The study included individuals with a BMI of 27-45kg/m2 that had two or more of the following: diabetes, hypertension, high triglycerides and a waist girth of ≥102 cm for a man and ≥ 88 cm for a woman. 2487 individuals were randomly assigned to receive placebo (P), 7.5mg phentermine + 46 mg topiramate (LPT) or 15 mg phentermine + 92 mg topiramate (HPT) for 56 weeks to assess weight loss as the primary outcome. The benchmark goal of the therapy was a10% reduction in body weight. At the onset of the study, all study patients were given a lifestyle modification manual and encouraged to implement lifestyle changes and reduce caloric intake by 500 calories/day.
Although it has been demonstrated that lifestyle modification programs are effective in reducing weight and improving the comorbidities associated with increased weight. These interventions require trained personnel and frequent office visits. One of the goals of the Conquer Trial is to produce a treatment that can be administered by family doctors without the need for counseling or frequent office visits.
After 56 weeks, change in body weight was -1.4 kg for the placebo group, -8.1 kg for LPT and -10.2 kgs for HPT. Twenty-one percent of P, 62% of LPT, and 15% HPT group achieved a 5% weight loss. Using the 10% weight loss threshold, 7% of P, 37% of LPT and 48% HPT reached the 10% threshold.
According to the authors, these results indicate that phentermine + topiramate with an office-based intervention may be a valuable treatment for obesity that can be safely administered in the family practice setting. I am confused. How can they say that? After 56 weeks, over half of the volunteers did not achieve the 10% weight loss goal. The greatest weight loss was 26.84 lbs, achieved by the high dose group. Furthermore, all participants in the study were instructed to make a 500 calories deficit per day in their food intake. Usually a 500 calorie deficit per day yields a pound/week weight loss. If executed, that is over 50 pounds lost from decreasing caloric intake during 56-week study period. Although study patients were assessed at week 2,4 and every 4 weeks thereafter, it was unclear if calories consumed were discussed.
When did obesity become a disease? Is it when health care and pharmaceutical industries decided they could profit from it? I do believe that being overweight or obese is a complex combination of factors. The fix is not as simple as more exercise or eating less unless humans are laboratory animals, completely controlled. However, human behavior encompasses intellectual, social, emotional, self esteem, and environmental factors. Becoming overweight is an insidious progression of events that show up as excess pounds and poor health. The fix of the problem needs to be unique to each individual. It must address the interaction of their psychological health with the environment they live in. A pill and a few minutes with the family doctor will hardly scratch the surface.
Obesity is classified as monogenic, syndromic or polygenic. Monogenic causes are those that occur from a single gene defect and are present within the first year of life. There are 6 mongenic forms of obesity: leptin deficiency (LEP), leptin receptor gene mutation (LEPR), pro-opiomelanocortin gene mutation (POMC), melanocortin 4 receptor gene mutation (MC4R), Pro-hormone convertase-1 mutation (PC1), and single-minded, drosophilia, homolog of, 1 gene (S1M1) mutation and neurotrophic tyrosine kinase receptor type 2 gene (NTRK2) mutation.
Syndromic obesity occurs in the context of a distinct set of clinical phenomena. There are about 25 such syndromic types of obesity that are identified and they are associated with the clinical pathologies such as mental retardation, dysmorphic features or organ specific developmental abnormalities.
Polygenic obesity is the where multiple common, interacting alleles contribute to the development of obesity. In humans, 61 common gene variants at 58 loci are associated with obesity phenotypes. With polygenic obesity, a poor lifestyle can upregulate the expression of obesity or a prudent lifestyle can stave off the expression of the obese phenotype.
About 70% of adult Americans are overweight or obese. The risk of a child becoming obese is 2.5 – 4 times greater if one parent is obese and up to 10 times higher if both parents are obese. The main thing to keep in mind is that genetic predispositions are like seeds. There are seeds for obesity, heart disease, diabetes, mental illness, etc. The way you live has an enormous influence on what genetic predispositions manifest. If you plant your obesity seeds in fertile soil: energy rich, nutrient poor foods, processed foods, minimal consumption of fruits or vegetables combined with low levels of physical activity; your obesity seed will flourish. If you live so that your obesity gene is starved or neglected, it will likely not flourish.
Unfortunately, medicine and pharmaceutical industry do not want you to feel so empowered. The media and advertising encourage individuals to look at health as out of their hands. Because we can’t choose our parents, get in the driver’s seat of your health and starve the unfavorable genetics we have been given.

It is known that apolipoprotein E (ApoE) gene variation is associated with a greater risk of Alzheimer’s disease; however, a couple of thought come to mind. First, would you want to know? Second, would you live any differently? Although the answers are unique to the individual, the story about genetic predisposition is not.  Genetics may have up to a 33% influence on the outcome, except in the case of familiar hypercholesterolemia. In that case if the genetic manifestation is on both sides of the family, the likelihood in offspring is extremely high.  However, most chronic conditions such as heart disease, diabetes and high blood pressure the genetics may have up to 30% of the influence on disease manifestation. That means that the individual has 70% control over whether the chronic condition manifests.  I view genetic predisposition like a plant.  If you put the plant in good soil, water it and giving the right amount of light; it should grow. To create a good environment for heart disease seed: have a sedentary lifestyle, eat a diet high in calories and saturated fats and fail to manage your stress. Then you are likely to get heart disease.  To create a poor environment for the heart disease seed: exercise daily, maintain a normal weight, consume a diet high in fiber and low in saturated fats. That’s a recipe for keeping heart disease at bay.  Despite the influence of genetics, it may be more important to assume that most chronic disease are interrelated and are greatly influenced by environmental factors. That is what you can control.

What are the factors that influence Alzheimer’s?  Alzheimer’s is characterized by the accumulation of beta amyloid plaques  and neurofibulary tangles.  It manifest initially as mild impairment in short term memory and progresses to more serious cognitive changes, many  in multiple domains leaving the individual with difficulties with speech, memory, orientation, learning, comprehension, judgment and the inability to perform normal activities of daily living.  I’d like to propose the idea that AD is in someway related to other chronic conditions that are inflammatory in nature. Keep in mind that the same blood that oxygenates your heart, muskuloskeletal system, digestive system, and all other organ systems also nourishes your central nervous system (CNS), your brain.  That would mean that if inflammatory proteins are transported via the bloodstream, they are transported to the CNS.

With all of that said, there is a recently finding of a rare type of Alzheimer’s that effects only about 2% of the population. It is referred to as Familial Alzheimer’s disease (FAD).  FAD is early onset meaning that it presents before the age of 65, and is inherited.  All offspring of an individual with FAD have a 50/50 chance of having it. Individuals with FAD have elevated beta amyloid plaques (AB42 protein), elevated tau and p-tau 181 proteins prior to the appearance of symptoms of dementia.

Over the last 20 years much research has been performed to illuminate this debilitating disease, their is still so much to learn about AD.  There are some modifiable risk factors that show an association with AD. Diabetes, high cholesterol in midlife, low levels of physical activity, depression are associated with a greater risk of cognitive decline. Whereas a diet high in fruit and vegetable consumption, low in saturated fats, moderate alcohol consumption, higher levels of educational attainment, ability to speak more than 2 languages and a high level of physical activity seems to offer a protective effect from AD.

So what to do to lessen the likelihood of having AD?  Living a lifestyle that will prevent the most common chronic diseases and engaging in activities that enrich your mind should be protective. Engaging in regular physical activity reduces the production of the precursor protein, naprilysin, to beta amyloid plaques.  It is also recommended that the type of exercise be varied. It challenges the neuromuscular system and the CNS.  Chronic volumes of physical activity attenuate the neural response to stress. Learning something new is good for the CNS as well. Engaging in hobbies or learning activities that are not part of your cerebral repertoire increase spatial memory, increase hippocampal neuronal development and increase neurotropin production. To get the best protection, combine cognitive and physical activities as they each provide distinct benefits to the aging CNS.

Early diagnosis?  In the August 2010 issue of the Archives of Neurology three biomarker were present in cerebrospinal fluid (csf) of 90% of the patients with AD and in more than 1/3 of normal adults.  The three biomarkers are beta amyloid protein, tau protein and p-tau 181.  These findings should influence the search for new treatments and a cure for AD.  Of the 5 medications that are currently used to treat AD, none of them target the pathways that produce the beta amyloid, tau or p-tau 181 proteins.  Furthermore, these medications are only effective for 6-12 months.  There is no cure for AD.

So for now, keep in mind that AD is NOT a normal part of aging and that maintaining overall general health and creating a lifestyle that promotes wellness is probably the best defense against any chronic disease, including AD.

This book is a series of interviews with 16 “Breakthrough Physicians” intermixed with Ms. Somers’ “8 steps”, anecdotal evidence and fan mail. “Breakthrough Medicine” is defined as an extension of anti-aging medicine where forward thinking Western physicians are attempting to prolong and preserve quality of life. It is a system where patients are treated like individuals who have their own special needs. Ms. Somers puts down our current medical system where doctors have little time to listen and use the prescription pad too often. Although, I believe our health care system has its faults. I don’t believe that physicians do not listen. I believe that most take the Hippocratic oath seriously!  She fails to mention that her doctors are in private clinics that do not take insurance. If you have money, please come and pay!

Ms. Somers’ 8 Steps to Wellness are a follows:

1. Get Bio Identical Hormone Replacement (HRT)

2. Avoid Chemicals and detoxify your body

3. Take Nutrition Seriously

4. Create a healthy GI Tract

5. Avoid Pharmaceuticals unless absolutely necessary

6. Supplement your diet

7. Exercise Regularly

8. Get Proper Sleep

Ms. Somers blames the cancer battle she had on taking oral contraceptives. She says that if she would have balanced all of her hormones with bio-identical HRT; she would have never had cancer. Her own regime is quite laborious and expensive. She takes 0.08mg of growth hormone in a shot daily, applies topical  bioidentical estrogen cream daily and for two weeks adds a topical progesterone cream. She has a glass of water with lemon juice daily to balance her liver, a B12 and B complex shot. Every other day, she also has a shot of iscador, which is made from mistletoe extract. Ms. Somers explains that Iscador is used in lieu of chemotherapy in the Rudolph Steiner Clinic. She believes in eating real foods and mostly organic. She has personal yoga instructor that comes several days a week and she professes to walk 40 minutes on the days she does not do yoga. She sleeps 9 hours a night and wakes up “refreshed”. To complete her regime she has a monthly “tune-up” with Dr. Michael Galitzer. At Dr. Galitzer’s clinic, she gets tested for fatigue and to see if all of her organs are working optimally. She usually has some homeopathic liver drops and an IV of vitamin C and glutathione. When she leaves, “she feels energized and refreshed.”

Of the 8 steps to wellness, the hardest one to swallow is her suggestion of bio-identical hormone replacement therapy. She blames the malaise, weight gain, cancer, Alzheimer’s disease and aging in general on hormonal imbalance. She discusses thyroid replacement, cortisol replacement, growth hormone replacement, testosterone replacement as well as estrogen and progesterone. She compares the production of commercial HRTs to bioidentical HRTs. She claims bioidenticals superior! In every interview, she attempts to steer the physician toward a favorable discussion of bioidenticals. It was infuriating to read! Nonetheless, most of the Breakthrough Physicians went along.

The Endocrine Society has a position stand on bio identical hormone replacement. The long and short of it is something like this: There is little scientific evidence to support the benefits of and/or adverse effects of either form of HRT. If both forms were equivalents in purity and dosage, then you would expect the risks and benefits to be the same. It is also unlikely that a simple saliva test could possible provide the information necessary to create customized hormone preparations. Furthermore, the FDA does not monitor, the final hormone formulations at most compounding pharmacies leaving purity, safety and dose uncontrolled. You can view the position stand at: www.endo-society.org/advocacy/index.cfm

Step number 2 is to avoid chemicals and detoxify your body. Ms. Somers recommends a few far out ideas, such as colonic therapy, building your immune system with intravenous vitamin C infusions, keeping you lymph system healthy with dry brushing and exercise (I agree with exercise), hyperbaric oxygen, chelation therapy, and infrared sauna. I do agree that staying away from unnecessary exposure to chemicals, eating fresh foods, preparing simple nutritious meals and exercise are healthful.  The whole idea of detoxifying is baffling to me. Do you eliminate regularly? If so, you are probably rid of whatever toxins are in your colon!

The rest of the recipe is pretty common sense, which is how one would hope people look at things. Taking nutrition seriously, getting 7-9 hours of sleep each night, regular exercise, avoiding unnecessary medications all make sense.  Unfortunately, more detail could have been given to the specifics of nutrition, exercise prescription and creating a sleep ritual. Ms. Somers promotes supplementing your diet and provides 7 pages of supplements that you can purchase through the Life Extension Foundation.  Although, the RDA for a few vitamins does increase for those over 55, a nutritionist or family practitioner should be consulted.

In my opinion, Ms. Somers is nothing more than an attractive grand marketer. She provides her list of “Breakthrough Physicians” in every state, along with a master herbalist, clinics to test your hormone levels and nutritional deficiencies, and compounding pharmacies. Her beauty care line and exercise products are available at www.SUZANNE.com.

The genetic defect that was responsible for “acelerated aging” was an inability to properly repair mitochondia.  Mitochondria are organelles within the cell that are responsible for producing energy.  They have their own DNA and multiply, during which they can accumulate small insults to the DNA and if they cannot repair, mutations occur in the DNA of the mitochondria which disrupt the ability to function normally. This is associated with aging, cancer and age related diseases.

Rodents are often studied in ageing models because the lifespan of a rodent is 1-2 years depending on the strain. The mice were split into two groups: those who did not exercise (control group) and those who ran 45 minutes 3x/week at a vigourous pace (which is equivalent to 8:30 nile pace).  Exercise began when the mice were 3 months of age (20 human years). At 8 months (60 human years) the exercise group had not grayed and did not demonstrate any age related decline or disease.

We know from human and animal studies that regular exercise promotes cardiovascular health, prevents type 2 diabetes, prevents certain types of cancer, promotes bone health, and reduces the risk of obesity.  This study demonstrates exercise modifies a cellular process involved in the aging of the cell and thus the organism. In the exercising mice, exercise altered systemic mice mitochondrial biogenesis,  prevented mitochondrial DNA depletion and mutations, increased oxidative capacity and respiratory chain assembly, blunted pathological levels of cell death in multiple tissue and restored mitochondrial morphology.  These adaptations demonstrate phenotypic protection, reduced multisystem pathology, and prevention of premature mortality.

What does this really mean?  Endurance exercise promotes systemic mitochondrial rejuvenation and offers a promising therapeutic approach to mitigating mitochondrial dysfunction in aging and related comorbidities. However, there are a few caveats that must be presented. First of all, although the benefits of regular physical activity to prevent obesity, heart disease and diabetes are well known; only 26% of adults participate in vigourous leisure time activity. This is evidenced by the 72% of men who are overweight or obese and the 64% of women who are overweight and obese. If we could get exercise in a pill, Americans would fall for it.  Unfortunately there are so many benefits that exercise affords, a pill wouldn’t do it.  Second, laboratory animals do not live the life that humans do. They lived in a controlled environment, with controlled meals, controlled stress and little if no exposure to natural sunlight.  Human, on the other hand are exposed to photoageing, and have multiple stressors (work, family life, financial, etc).

I believe the results of this study are promising; however, the life of a human is much more complex than the life of a laboratory animal.  Exercise may not be the fountain of youth; however, it is the foundation of a lifestyle that promotes good health, longevity, and well-being. If exercise is the foundation, the remaining ingredients for a long life should include rest, good nutrition and meaningful relationships.

The study continued for 18 more months to examine the effects of the supplements on joint function (as defined by the change in joint space width) as well as pain. A change in joint space width of less than 0.2 mm would indicate a slowing of the loss of cartilage. This would indicate a slowing f the progression of the disease. The results of cartilage loss were as follows: G 0.013; C 0.107; GC 0.194, Celebrex 0.111 and placebo 0.166. They also measured disease progression and found that those with grade 2 osteoarthritis were less likely to have progression and about 24% of those taking GC showed disease progression compared to placebo. These results were published in the journal Arthritis and Rheumatism October 2008.
The most recent results from the Gait Team were published in June 2010 in Annals of Rheumatic Disease. The primary outcomes were pain and structural damage. They found that after 24 months of treatment there was no significant difference in any of the treatments as compared to placebo. What that means is that patients who took, GC, G, or C had similar outcomes to patients who took Celebrex or placebo. Side effects were minimal and did not differ significantly among the groups.
What is next…there is a clinical trial titled: Efficacy and Safety Study of Glucosamine/Chondroitin Sulfate to Patients Treatment With Osteoarthrosis of the Knee (Artico) that is not yet open. It can be found on clincaltrials.gov. It looks similar to the GAIT and is sponsored by Eurofarma Laboratorios Ltda.
For some, glucosamine chondroitin sulfate may seem effective. Maybe it is a placebo effect, because the doctor said to take it. Do we want a pill for everything? Not me. I would recommend some weight loss, swimming or cycling, muscle strengthening and stretching for 24 weeks and see what happens. You might just get healthier and happier.

Chapter 6: Helping Americans Make Healthy Choices. This chapter sums up the multifactorial influences on diet and activity choices. Figure 6.1 breaks it down into 4 domains: individual factors, environmental settings, sectors of influence (government, education, marketing, food industry) and social and cultural norms (priorities, beliefs, religions, family values). The chapter also presents the 2010 Dietary Guidelines Call to Action’s Three Guiding Principles. They are: 1) Ensure that all Americans have access to nutritious food and opportunity for physical activity. 2) Facilitate individual behavior change through environmental strategies. 3) Set the stages for lifelong healthy eating, physical activity, and weight management behavior. What they fail to do is give a call to action. They state early in the document that childhood eating habits lead to overweight adults. They fail to make an appeal to the parents that they have to “walk the walk.” Having access to nutritious food and opportunities for physical activity doesn’t mean that we will do it! What environmental changes have they made? The return of physical education and healthier school lunches is a great start. What about the family system? What behaviors and attitudes are learned at home? What stages have they set? Individuals can easily think that its not any fault of their own that they have type 2 diabetes and now the healthcare system must care for them. What we need is some hard-core accountability. Being soft with position statements and guidelines isn’t working.

On the other side, there is a real advantage to eating some of those “good” foods. Foods that are found in the produce section, consumed raw and in the words of others, “taste bland” are considered good.  Good foods are whole grains, fish, fruits and vegetables. Nutrient rich foods that not only fuel your body; they nourish your cells in a way that prevents chronic disease and promotes good health.
So don’t over-think things! It is just food! Having cake or anything you love in the context of energy balance will not hurt you. Stop feeling like some foods are “forbidden fruits” and get out of the Garden of Eden. You will only be more successful at longterm weight maintenance and health.
Remember, the media’s job is to sell the next new food craze. Use your common sense.

She said that the new job required her to be in the office by 8:30 and work until 5. For her, it was challenging to shift to getting up early in the morning and making time after work was hard also. Weekends work well for her. I shared with her a little rule that I have used in times that I was pressed for time and with many clients who had barriers in their thinking regarding exercise.

I told her to get up 15  minutes early and run for ten minutes. That will be the equivalent of 5 miles she wouldn’t be running. It will put her mind in a great frame for the day and it will help her be consistent. Consistency is the backbone of long term fitness. So 10 minutes is better than no minutes and the benefits add up! Apply the “ten minute rule”.

Research has also demonstrated  that 3 ten minute exercise bouts has the same metabolic and caloric expenditure equivalent of a single exercise bout. So don’t berate yourself when you don’t have 30 minutes, try a few shorter workouts.

If time is not your issue and you just don’t feel like exercising, the ten minute rule applies. Just try to workout for ten minutes and see how you feel. Usually after 10 minutes you are in a groove and can continue for longer. If you don’t feel better, stop and feel good about the 10 minutes of exercise you gave yourself that day.