February 10th, 2016

Unraveling Obesity? All Roads Lead to the Brain!

newsletter-bannerIntroduction:

As scientists strive to find answers to the modern epidemic of obesity-related health problems, they are discovering a complex system within the brain that is playing a huge role in fueling the lower quality of life and dramatic rise in health-care costs that are the consequences of this epidemic. This new information is important to you because it is finally helping lead to practical applications of dietary and lifestyle that provide help to people desperate to lose weight.

The medical journal Obesity just this week focused an entire issue on recent discoveries relating to the role of the brain in promoting obesity. In this newsletter, I would like to focus on the key discoveries that I think offer the greatest impact today.

Background Data:

Mechanisms in the brain underlie both the states of loss of appetite (anorexia) and excessive appetite. Seemingly at odds with each other, these two different states share many common key features. Both reflect alterations in central control mechanisms that perpetuate the disturbed appetite control and also lead to the metabolic complications of severe weight loss in the case of anorexia and, obesity and insulin resistance.

The brain is the master conductor coordinating the changes in appetite required to maintain our nutritional status. This makes a lot of sense because the brain is the most metabolically active organ in the body accounting for about 40% of our required nutrition in order to function properly. It is going to fight to survive.

Brain cells throughout the entire brain, but highly concentrated in some specific brain areas, are able to sense nutritional status and relay this information other areas of the brain to affect both metabolism and appetite. What scientists are discovering is how the brain integrates information about short-term changes in nutrient availability within the context of long-term energy status. For example, they have found that the same signal can cause different responses in the brain depending on nutrient status and insulin sensitivity. If food is plentiful and is being handled properly, the brain can respond to this signal with feelings of satiety. If on the other hand, if a person is starving or in the case of insulin resistance, the same signal from brain cells is interpreted as something entirely different and can lead to intense feelings of hunger and a slower metabolism. In both anor exia and obesity, the response to the signal is crossed.

The therapeutic goal in either the case of anorexia or obesity is to help restore the brain’s interpretation of the signals affecting appetite control to reset so to promote restoration of proper body weight and metabolism.

New Data:

The recent issue in Obesity featured research presented at a gathering of seventy scientists from around the world in Switzerland over a week in the Fall of 2014. The program was titled “All Roads Take to the Brain: Neural Control of Energy Homeostasis in Health and Disease.” The goal was to bring these scientists together so that they could share and provide their insights on how the brain controls eating and calorie balance. Many important discoveries were presented. Here are some that I found the most interesting:

– Men and women have differences in the key areas of the brain that control appetite and metabolism. Interestingly, although obesity affects both males and females rather equally, premenopausal women have less diabetes, high blood pressure, and other complications of obesity than man. So, the effect of obesity is different between men and women. Specific receptors for estrogen in the hypothalamus of the brain in women protect them from obesity-associated metabolic complications. After menopause there is a tremendous rise in obesity and its complications in women. With the drop in estrogen after menopause, this protective effect of estrogen is lost. Overcoming the loss of this estrogen protection requires taking advantage of backup mechanisms in postmenopausal women that control appetite and metabolism (see comments below).

– The intestinal hormone glucagon-like peptide-1 (GLP-1) is emerging as the most important gastrointestinal peptide because of its unique effects in potentiating the effects of insulin along with a multitude of other effects that ultimately promote powerful feelings of satiety.

– The brain endocannabinoid system (ECS) refers to the complex interactions that are controlled by our own internal compounds that mimic the effects of external cannabinoids such as those compounds from marijuana and hemp. Any alterations in ECS signaling promotes the development of obesity, insulin resistance and elevations in blood lipids. Correcting this disturbance is a key target for obesity and metabolic disorders.

Commentary:

My experience with many scientists is that are phenomenal at describing dots, but often not so good at connecting them. Here are my takeaways from the research highlighted above that connects them with some practical recommendations.

Postmenopausal women need support to counteract the drop in estrogen. For example, they need to improve the gut microbiome, improve insulin sensitivity, eat more raw vegetables, and utilize conjugated linoleic acid (specifically Tonalin). One of the studies that I highlighted in a newsletter last year showed that women, but not men, given Lactobacillus rhamnosus lost twice as much weight after 12 weeks of compared to the placebo group. This result was quite curious, but indicates that women may be more sensitive to alterations in gut flora and their effect on insulin sensitivity and appetite. The recommendations to improve insulin sensitivity and eat more raw vegetables (especially greens) is also based upon recent studies showing a heightened response to these actions by women. Lastly, conjugated linoleic acid in the form of Tonalin has shown the most positive results in postmenopausal women (typical dosage 1,000 mg three times daily). Other forms of CLA have just not shown consistent of results. The benefits of Tonalin may reflect unique influences in regulating several sites of action, including effects on the endocannabinoid system in women (see below).

In regards to GLP-1, I have previously highlighted the tremendous ability of the dietary fiber matrix known as PGX to increase GLP-1 formation and release. PGX is the most viscous and soluble fiber ever discovered. PGX has been shown to produce a significant increase GLP-1. This hormone is secreted by specialized cells known as L-cells in the small intestine and colon in response to food intake. PGX not only leads to pulses of GLP-1 release into the bloodstream as it passes throughout the entire digestive tract it has also been shown to increase the number L cells within the intestinal tract. This mechanism explains the prolonged effect of PGX on feelings of satiety. For more information, see PGX. Other foods that increase GLP -1 release include whey protein, high fiber intake, and green leafy vegetables.

Lastly, in regards to the endocannabinoid system, keep in mind that it is a lipid-based brain system. This means that it is largely based upon the influences of fats. Dietary fats are absolutely critical for this system to work properly. In particular, it requires the mono-unsaturated fats from nuts, seeds, olive oil, and avocadoes to function properly. It also seems to be critically dependent upon the long-chain omega-3 fatty acids found in cold-water fish like salmon as well as in fish oil supplements (take 1,000 to 3,000 mg EPA+DHA daily). Conjugated linoleic acid may also be a factor, especially in post-menopausal women.

Reference:

Westerterp-Plantenga M (ed.). All Roads Lead to the Brain. Obesity 2016:40(2).

January 26th, 2016

Does the Source of Selenium Matter in Cancer Prevention?

selenium benefitsIntroduction:

What if some of the large clinical studies assessing the benefits (or risks) of selenium supplementation in cancer prevention have used the wrong form? That looks to be the case as a new study from the University of Miami sheds light on the different effects of selenium-rich yeast versus another form of selenium known as selenomethionine. What the researchers have discovered is that there are proteins produced when making selenium-rich yeast that have anti-cancer properties beyond simply providing a source of selenium.

Background Data:

The results from studies looking at selenium in prostate cancer prevention have shown conflicting results. These may be related to the form of selenium being used. In the Nutritional Prevention of Cancer (NPC) study, supplementation with SelenoExcell, a selenium-enriched yeast, was associated with a 52% decrease in the development of prostate cancer. In contrast, in the SELECT study, selenomethionine failed to show any protective effects alone or when combined with synthetic vitamin E. The difference in results may be entirely related to the form of selenium being used. Here are some possible explanations for these conflicting results:

  • Selenomethionine has been shown to have only a modest effect in increasing prostate tissue selenium levels. In contrast, SelenoExcell is significantly more effective in increasing selenium levels in prostate tissue, especially at the 400 mcg selenium per day dosage.
  • In a clinical trial in men, only SelenoExcell was shown to significantly decrease markers of oxidative stress. When the men received selenomethionine there was no decrease in these same markers.
  • In the process of incorporating the selenium into the yeast it leads to the productions of yeast proteins that reduce cancer cell growth in experimental studies. These proteins may contribute to the overall superiority of SelenoExcell versus other forms of selenium.

In addition to selenomethionine, there are inorganic selenium salts like sodium selenite available in the marketplace. However, selenium salts are less effectively absorbed and are not as biologically active compared to organic forms of selenium, especially SelenoExcell.

New Data:

Researchers evaluated the effects of a group selenium-containing compounds from selenized yeast known as selenoglycoproteins (SGPs). The SGPs were evaluated for their impact on the interactions of lung and breast tumor cells with cells that line blood vessels (endothelial cells). Currently there are no therapies aimed at preventing the spread of cancer by specifically targeting the adhesion and migration of tumor cells into other areas of the body. Results from the detailed study showed that SGPs extracted from Se-enriched yeast possess the ability to reduce the adhesion of tumor cells to endothelial cells. In addition, the researchers also showed that SGPs also blocked the migration of tumor cells into underlying tissue. Furthermore, SGPs were shown to block the tumor promoting effects of nuclear factor kappa-B (NF-κB). This action has profound influence as NF-κB is a master regulator of proinflammatory reactions and gene expression. NF-κB activation is a key factor in cancer cell growth and metastasis. By blocking NF-κB, the SGPs have an effect far beyond the action of simply providing a form of selenium.

Commentary:

These results are extremely provocative. If the science above is confusing, let me try to restate what it is telling us. Basically, it has long been assumed that selenium-rich yeast was beneficial because it provided a superior form of selenium. Once absorbed the selenium would be utilized as a valuable antioxidant as part of an antioxidant enzyme known as glutathione peroxidase. What the emerging science indicates is that the selenium-containing proteins that are produced in the process of making selenized yeast may turn out to be more important than the selenium itself. In other words, these proteins may be the real protective factor.

Learn more about the benefits of SelenoExcell.

Reference:

Wrobel JK, Choi JJ, Xiao R, et al. Selenoglycoproteins attenuate adhesion of tumor cells to the brain microvascular endothelium via a process involving NF-κB activation. J Nutr Biochem. 2015 Feb;26(2):120-9.

Dr. Michael Murray
1/26/16

December 15th, 2015

Light Therapy is More Effective than Prozac in Major Depression

lighttherapyIntroduction:

Bright light therapy has a proven track record of success in the treatment of seasonal affective disorder (SAD), commonly referred to as the winter blues. A new study from the University of British Columbia shows that this simple and safe therapy is effective for non-seasonal major depression. In fact, researchers showed light therapy was much more effective than fluoxetine (Prozac).

Background Data:

During the winter months, sufferers of SAD typically feel depressed; they generally slow down, oversleep, overeat, and crave carbohydrates. In the summer, these same people feel elated, active, and energetic. Although many variables may be responsible for SAD, the lack of exposure to full-spectrum natural light appears to be the most logical explanation. The antidepressive effects of full-spectrum light therapy have been demonstrated in well-monitored, controlled studies in SAD.

The typical protocol used in clinical studies involved using specialized light boxes providing full-spectrum fluorescent tubes vs. regular tubes. Patients were then instructed to sit three feet away from the light anywhere from 30 minutes a day, up to three hours total, in morning and evening.

The antidepressant effect of light therapy is thought to be due to restoring proper melatonin synthesis and secretion by the pineal gland leading to re-establishment of the proper circadian rhythm – the normal rhythm of hormone secretion that occurs each day.

New Data:

Led by noted SAD and light therapy expert Raymond Lam, M.D., the UBC researchers randomly assigned 122 patients with major depression to either light therapy alone for 30 minutes a day; a placebo device, which did not provide full-spectrum lighting; the combination of light therapy plus fluoxetine, 20 mg a day; or the placebo device plus a placebo. Approximately 30 patients were enrolled in each of the four treatment groups.

All of the patients had a score of 20 or higher on two different standard scales of depression (HDS and MADRS) when the study started indicating significant depression. Furthermore, the duration of the current major depressive disorder episode ranged from a low of 45 weeks to 90 weeks.

Light therapy consisted of 30 minutes a day of exposure to a full-spectrum fluorescent light box as soon as possible after awakening. At the end of the 8-week treatment interval, mean changes in the depression score from baseline (MADRS) were significantly greater among those who received bright light therapy alone, compared to fluoxetine alone. Most significant was that 43.8% of the patients getting the bright light therapy went into remission compared to only 19.4% of the subjects taking fluoxetine. Best results were seen with combination of bright light therapy and fluoxetine than for any of the other treatment groups with a 58.6% remission rate.

These results show quite clearly that light therapy possesses an antidepressant effect even in non-seasonal major depression.

Commentary:

Light boxes similar to those used in clinical trials are available online and generally cost between $69 and $199. An alternative is to get outdoors in sunlight for 30 minutes a day or replace standard light bulbs with full-spectrum light bulbs in areas of your home or office where you spend a considerable amount of time.

Here are some other recommendations for SAD since it is that time of year:

  • Melatonin supplementation alone has produced mixed results in clinical trials in SAD. Nonetheless, some people do seem to respond to 2-3 mg of melatonin at bedtime and for further support in resetting their biological clock. I recommend taking the special form of vitamin B12 (methylcobalamin) at a dosage of 3-5 mg the first thing in the morning.
  • Vitamin D3 is absolutely essential for proper brain chemistry and neurotransmitter action. To insure optimal vitamin D status during the winter months, most health experts, myself included, are advocating daily dosages of 2,000 to 5,000 IU, even in apparently healthy adults.
  • John’s Wort extract (SJWE) has shown to be very effective in reducing depression scores in patients with SAD and can be used to enhance the effects of the bright light therapy instead of standard antidepressant drugs. Typical dosage is 900 to 1,800 mg daily. Because SJWE can increase the activity of a drug detoxifying enzyme in the liver, it has been found to decrease the plasma concentrations of a long list of drugs. As a general rule, if you are taking any prescription medication, including birth control pills, do not take St. John’s wort without approval from your physician.

Reference:

Lam RW, Levitt AJ, Levitan RD, et al. Efficacy of Bright Light Treatment, Fluoxetine, and the Combination in Patients With Nonseasonal Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2015 Nov 18:1-9.

Dr. Michael Murray
12/15/15