Wednesday, August 12, 2009

Morbid Obesity, Vitamin D Deficiency, and Swine Flu

The world is bracing itself for the coming winter onslaught of the swine flu. While most people who succumb will find it no different in symptoms and severity from other bouts with the flu, some whose resistance is weak will develop complications like pneumonia, which will progress to septic shock, multiple organ failure, and death. Compared to past flu seasons, children will be over-represented among those who die of swine flu, because most of the elderly have antibodies due to previous exposure to H1N1 virus that was widespread before 1956.

Through observation of those who end up in the emergency room with swine flu, it has become apparent that morbid obesity is a strong risk factor (Obesity and Swine Flu) . In Japan, only 1.6% of adults are obese. Correspondingly, in over 2,000 confirmed cases of swine flu, none of the victims died or even became severely ill. In Manitoba, Canada, 60% of the patients who showed up in intensive care units were obese. Similar observations of a correlation with obesity and flu complications have been reported from cities around the world, including Glasgow, Melbourne, Santiago, and New York City.

Since the United States is in the midst of a childhood obesity epidemic, it stands to reason that, among the nations of the world, children in the United States will be among the hardest hit by the coming flu epidemic. Exactly why obesity is a risk factor is not clear. Suggestions have been made that excess fatty tissue may compress the chest and make breathing difficult, or that the obese are physically out of shape and therefore have less efficient lungs, or that insulin resistance may leave them vulnerable to septic shock due to excess sugar in the blood.

The United States is also facing an epidemic in childhood vitamin D deficiency. An article that just appeared in the journal Pediatrics [9] claims that 7 out of every 10 children in the U.S. have vitamin D levels that are too low. Vitamin D deficiency -- a level below the bottom of the normal range -- was observed in 1 out of every ten children. This is a serious condition that can lead to severe problems with bone development, as well as many other negative consequences, related to both the immune system and brain development.

Vitamin D has been shown to provide protection from the flu [4] (Vitamin D Protects from Flu) . In a study involving 19,000 people, it was discovered that people with vitamin D deficiency were 36% more likely to catch the flu, and if they also had asthma their increased risk was five-fold. Vitamin D deficiency is also a clear risk factor for sepsis [7], otherwise known as blood poisoning, which is often the final blow when the disease process advances from flu to pneumonia and subsequent multiple organ failure.

Intriguingly, there is a strong connection between obesity and vitamin D deficiency. Many studies have confirmed that the morbidly obese often have extremely low levels of vitamin D in their blood [1][2]. So children who are obese are more likely to respond badly to the flu, but also more likely to get it, due to their vitamin D deficiency. In fact, I believe that their vitamin D deficiency is the main factor that puts them at greater risk of dying.

Thus, America has been put in a double-jeopardy situation, with simultaneous vitamin D deficiency and obesity epidemics. If we can get at the underlying cause, then we can begin to turn around this trend and greatly improve the long-term health prognosis of our nation's children. I believe that some answers can be found by studying fat metabolism and the critical roles played by vitamin D and calcium.

Before reading further, I would suggest that you take a look at this article that appeared in the Washington Post in 2004 (Active Life of Fat Cells) . I will begin by quoting from their introduction:

"For decades, scientists thought fat cells were passive blobs that did nothing more than store energy, bloat flabby hips and bellies, and perhaps wear down the body by forcing it to cart around a lot of extra weight.

But as the nation's obesity crisis has intensified scientific interest in fat, researchers have fundamentally altered that view: Fat cells, they now realize, are extraordinarily dynamic, complex and influential entities that affect a staggering array of crucial bodily functions."

Fat is now referred to by scientists as a third "endocrine organ:" it releases a complex array of hormones and proteins that, together with hormones released by the thyroid and adrenal glands, orchestrate many body functions. Fat cells dispatch chemical signals to many other organs of the body, including the brain, liver, muscles, reproductive organs and the immune system.

Below, I will develop an argument that obesity is in many cases a consequence of the excessive need for fat cells to store critical nutrients that are inadequately supplied through nutrition. The fat cells themselves release signals that are transmitted through the blood to the appetite control center to cause the person to overeat. One of the critical deficient nutrients is fat itself, but the body is able to manufacture fat from sugar, so excess carbs in the diet can be converted to fats and stored on the body. The fat cells can then release their fat stores whenever there is a need -- for example at night when the body switches over to a fat-metabolism mode and uses the fat to grow new neural pathways or reinforce old ones in the brain. When there is a deficiency in calcium and vitamin D as well, the fat cells' ability to release their fat stores is greatly impaired. Since the delivery rate for each fat cell is significantly lower than would be the case if these two nutrients were sufficient, more fat cells are needed to achieve the same supply rate.

If I am right, then the good news is that two simple lifestyle changes could lead to a significant reduction in both obesity and vitamin D deficiency. The first would be to throw away all soft drinks and replace them with whole milk. The second is to spend more time outside, notably without sunscreen protection.

Soft drinks promote obesity because they provide no nutrients except dissolved sugar, which is digested very quickly causing insulin levels to shoot up. Even diet soft drinks are not the answer. Surprisingly, they also induce weight gain: it is hypothesized that the sweet taste fools the body into expecting sugar, and insulin is released anyway even though the drink contains nothing to digest. (Diet Soft Drinks and Weight Gain) . The overabundance of insulin increases appetite and the child subsequently overeats.

Whole milk, on the other hand, provides three principle ingredients that, in my opinion, are crucial in the fight against both obesity and disease: calcium, vitamin D, and fat. Given today's climate in which fats are much maligned, you may be surprised that I am specifically recommending whole milk as opposed to, for example, nonfat milk. However, the fat in whole milk is at least as important as the vitamin D and the calcium in promoting weight loss. Part of the reason is that the fat is critical to promote the absorption of both vitamin D and calcium [15]. But I will further argue that inadequate fat in the diet may be one of the most significant drivers for our current obesity epidemic, by creating a "fat deficiency syndrome" and consequently programming the body to convert starches to fat and store them in the midrift to provide a steady supply of this essential nutrient, given its dietary insufficiency. Getting fat is a much more significant risk factor to heart disease than eating fat.

Both vitamin D and calcium are much less effective if the other one is deficient. In a careful study of previously published and new studies on the relationship between calcium and vitamin D, Heaney [13] observed that both the blood serum level of vitamin D and the degree to which it is effective both in bone health and in other areas such as cancer protection are dependent upon an adequate supply of calcium in the diet. Furthermore, both of these nutrients are significantly less well absorbed if fat is not available in the gut to promote absorption [15]. Thus these three nutrients all depend on one another to carry out their biological roles. Whole milk (and, more generally, high-fat dairy) provides all three, and hence drinking whole milk is remarkably effective for solving the problem of deficiency in both vitamin D and calcium.

The reason for getting outside is to accumulate as much vitamin D as possible by exposure to the sun, not only because vitamin D plays a crucial role in fighting infection, but also because vitamin D is necessary for efficient metabolism of calcium, and this in turn leads to a reduced need for fat cells. Sun exposure is by far the best way to obtain vitamin D -- it is the preferred method from nature's standpoint, and it assures a good supply of vitamin D in the skin to fight off skin cancer. Just twenty minutes in the sun every day is more than enough exposure to manufacture all the vitamin D you will need. Ironically, the widespread use of sunscreen over the past two decades has led to an increase in the incidence of skin melanoma [10] by about 3% per year since sunscreen usage started to gain popularity in the 1970's. This is in my view directly attributable to the fact that sunscreen with an SPF of 8 or greater completely blocks the body's ability to manufacture vitamin D in the skin, while still not protecting from the very dangerous highest frequency rays of the sun. Vitamin D is nature's version of sunscreen, and it protects against all cancers, not just skin cancer, in addition to its many other roles in maintaining health.

The Complex Interplay among Calcium, Vitamin D, and Fats

Given the American Medical Association's persistent message that Americans should eat as little fat as possible and get as little sun as possible, the consequence is a nationwide epidemic in deficiency of three critical elements: calcium, vitamin D and fat. These three nutrients work together in a coordinated fashion to tightly regulate many biological processes, most notably for our discussion, brain development and the immune system. A consequence that has become very apparent is the alarming increase in brain disorders like Attention Deficient Hyperactivity Disorder (ADHP), Asperger's syndrome, and depression, and corresponding increase in immune system malfunction manifested as allergies, asthma, and perhaps even the rise of Lyme disease.

A hypothesis I propose is that, to try to compensate for a deficiency in all three of these critical nutrients, two distinctly different coping strategies have evolved in America's children, one that tries to store fat on the body and the other that tries to conserve fat depletion in brain development. Both strategies lead to distinctly different but equally dire consequences in terms of health issues. The "silo" strategy is to grow a profusion of fat cells on the body and use them to squirrel away fat, vitamin D and calcium. The fat that's accumulated in the fat cells can be manufactured by the body directly from other food sources. By up-regulating appetite, biological mechanisms signal to the child to eat an excess of the carbohydrates readily available to him. Insulin production goes into high gear, and the carbs are broken down, converted into fat in the liver, and ultimately stored in fat cells dispersed throughout the body, although perhaps concentrated around the midrift. The child then has to cope with all the consequences of metabolic syndrome, including an increased risk to later heart disease and type-II diabetes, as well as a variety of immune system disorders like allergies and asthma. However, at least there is now an on-hand supply of fat readily available to support brain development.

The alternative is to stay thin but conserve the body's fat consumption, for instance, by sacrificing certain aspects of brain development, such as the long-distance pathways necessary for processing external stimuli. This then leads to conditions like Asperger's, where social interaction is seriously impaired, or Attention Deficit Hyperactivity disorder (ADHD), where processes associated with attention are malfunctioning. The myelin sheath that coats the nerve fibers connecting up all the nerve cells in the brain and that is critical for insulating the fibers is made up entirely of fat.

There is a remarkable interplay among calcium, vitamin D, and fats in terms of the ways in which they support one another [6]. Vitamin D acts as a catalyst for calcium transport across membranes. With inadequate vitamin D, calcium is poorly absorbed from foods, so a vitamin D deficient person needs to consume more calcium to achieve the same effect as someone who has enough vitamin D. Vitamin D is very poorly assimilated if taken orally unless it is accompanied by fats. Nature never expected to have to cope with vitamin D in the absence of fat, because it is only found in fatty foods. Fats are responsible for storing vitamin D in the body, and hence they are an important source of it. For example pork lard and butter are both excellent sources. A diet that has eliminated animal fat is essentially a diet without any vitamin D.

Calcium Deficiency Leads to Weight Gain

Quite by accident, it has been discovered that calcium supplements act like a diet pill for obese people and for obese mice alike [12][16][18][19]. During the course of a clinical trial investigating whether calcium would help reduce blood pressure in obese African-Americans [18], it was accidentally discovered that the subjects experienced an unexpected beneficial side effect which was weight loss. After increasing their daily calcium intake by from 400 to 1000 mg/day, over the course of a year, the subjects' body fat was reduced on average by 10.8 pounds.

In a follow-up study of transgenic mice expressing the agouti gene, known to correlate with a predilection to obesity, the mice that were fed a high-calcium diet were found to gain much less weight than the controls, who were fed a high-sugar, high-fat diet. The amount of weight gained by the control group was 39% higher than the amount gained by mice that were fed a high-dairy diet. Mice that were given a high calcium diet but without the dairy were also better off than the controls, but their percentage improvement was only 24%.

These changes were consistent with measures of enzyme expressions that control for fat manufacture and break down. The mice who received calcium had a 51% inhibition of expression of a catalyst for fat synthesis, and a 3.4 to 5.2 fold increase in expression of an enzyme that breaks down fat, compared to the control group. Apoptosis (programmed cell death) of fat cells was also observed; i.e., the number of fat cells went down. These results were all statistically highly significant.

In [17], the authors state, "Dairy sources of calcium exert markedly greater effects which are most likely attributable to additional bioactive compounds in dairy which act synergistically with calcium to attenuate adiposity." "Attenuate adiposity" means "reduce body fat." What might these additional compounds be? I would claim that they are fats! In fact, a study on pre- and peri-menopausal women [15] (Dietary Fat and Calcium Absorption) , which examined the relationship between their ability to absorb calcium in the diet and their dietary habits found that the most significant factor that led to better absorption of calcium was dietary fat, with a highly significant P value of 0.001. A factor that negatively impacted calcium absorption was dietary fiber. So a high-fiber, low-fat diet, probably considered a healthy diet by many people, is particularly bad for calcium absorption. People who were overweight were also less efficient in absorbing calcium than people with a low body mass index. This is likely related to their low vitamin D status, since vitamin D plays an absolutely crucial role in promoting calcium transport.

Why does calcium deficiency lead to weight gain? The answer, according to Zemel, the lead researcher in the above studies, is something that at first seems counter-intuitive. In the presence of calcium deficiency, an increase in the regulatory parathyroid hormone triggers the body to want to horde both vitamin D and calcium in fat cells. Excess amounts of these substances in the fat cells triggers them to reproduce, and also to store additional fat. This in turn increases the appetite, in order to allow more fat to be produced, leading to excess food consumption and weight gain in the form of excess fat. The excess fat is preferentially piled up centrally on the midrift rather than distributed over the limbs. This effect might also partially explain why so many obese people are vitamin D deficient: their body is dumping all the vitamin D that they generate directly into their profusion of fat cells as soon as it is produced, so it is never able to stick around in the blood stream. When the calcium deficiency is corrected through an enrichment in calcium rich foods, the hording process abates, and the number of fat cells is pruned down.

I interpret this very simply to mean that, when there is a deficiency in calcium, the body "decides" to horde it, in order to have it available for critical needs. The only way it knows how to store it effectively is in fat cells, so it needs more of them. I think the same thing applies to both vitamin D and fats as well. So when a person is deficient in all three, they need to have a large quantity of all of them stored in a "silo" around the midrift. When there is a vitamin D deficiency, the efficiency in calcium metabolism is greatly reduced, so even more calcium is needed, for example in bone growth or in fighting infection, than would be the case for someone without vitamin D deficiency.

Vitamin D Deficiency Leads to Weight Gain

While vitamin D is known mostly for its ability to metabolize calcium for strong bones and teeth, it plays a crucial role in many other critical aspects of biology, one of which is associated with regulatiing the amount of fat that is stored on the body. In a DNA microarray study examining which genes are triggered in fat cells by the presence of vitamin D, a total of 93 genes were identified to respond, many of which were associated with the generation and destruction of fat cells [13].

The vitamin D in fat cells influences the efficiency of the fat cells' ability to store and release calcium. And calcium plays a critical role in the storing and releasing of fats. Thus a vitamin D deficient person needs more calcium to get the same level of efficiency from the fat cells as a person who has adequate vitamin D. It stands to reason, then, that increasing the amount of vitamin D available to the fat cell is in some sense equivalent to increasing the amount of calcium, because it improves the ability of the fat cell to use the calcium that it has available.

There is plenty of evidence that vitamin D deficiency is associated with obesity, but this does not necessarily mean that vitamin D deficiency causes obesity. However, a recent study assessing the direct relationship between serum vitamin D levels and weight loss while dieting (Vitamin D Promotes Weight Loss) , found a consistent linear relationship between the amount of vitamin D in the blood and the amount of weight lost -- subjects who had more vitamin D at the start of the study lost more weight. Each 1 ng/mL increase in the vitamin D measure was associated with an additional half pound of weight loss during the diet.

A novel argument for why exposure to the sun may promote weight loss was proposed by Foss [3] in March of this year. It is commonly accepted that there exist control mechanisms which maintain body weight at a set point through homeostatic pathways. These authors state, "Common obesity and the metabolic syndrome may ... result from an anomalous adaptive winter response. The stimulus for the winter response is proposed to be a fall in vitamin D." It has been determined that vitamin D evolved in primitive organisms as a UV-B sensitive photoreceptor which can signal changes in sunlight intensity. When a person wears sunscreen all the time, the body becomes fooled into thinking that they live in a climate with an anomalously weak sun. This implies that they will need to develop a layer of fat to provide insulation from what surely must also be a very cold climate, since in the past a weak sun was always associated with cold weather.

A study done in northern Norway [8], where the sun is very weak and therefore a poor source of vitamin D, looked at the relationship between vitamin D intake from food sources and body mass index. They found a negative association between body mass index and vitamin D, for both men and women, with a highly significant P value (< 0.001). This means that people who were overweight consumed less vitamin D in their diet.

Low Fat Diet leads to Weight Gain

Because it has become common dogma that eating fat makes you fat, I can predict that most obese people in America are arduously avoiding fats in their diet, which, I believe, is the exact opposite of what they should be doing. Children especially need fat, because it is a crucial nutrient for the brain, and children's brains are developing rapidly, growing many new neurons as well as axons and dendrides to connect up all the existing neurons. In my view, an option for children who aren't getting enough fat in their diet is to accumulate a fat supply on their body. Then, fat will be available whenever it is needed for biological functions, most notably, for brain development.

I highly recommend three excellent books that tell a consistent and compelling story about health: fats are good for you; it's the empty carbs that are bad. The book, "Good Calories, Bad Calories," by the New York Times reporter, Gary Taubes [14], shows a slice of bread and butter on the front cover; the message is that the bread is bad and the butter is good. The second book, "Fat and Cholesterol are Good for You," was written by Uffe Ravnskov [11], a Swedish M.D., Ph.D. who has long been obsessed with getting out the message of his book title. The third book is "Trick and Treat", by Barry Groves [5]. This book also argues for a low-carb diet rather than a low-fat diet. However, it also devotes an entire chapter to the subject of vitamin D, which is so intimately associated with animal fats that it becomes unavailable in a fat-free diet. When you compound this with obsessive avoidance of the sun, it's no wonder that Americans are in the throes of a vitamin D deficiency epidemic.

All of these books mention numerous studies in which different groups of people were put on different kinds of diets: high carb diets, high fat diets, and high protein diets. Consistently, the ones on the high carb diets fared the worst, in terms of losing little or no weight, and feeling hungry all the time. The ones on the high fat diet did the best: lost the most weight and felt the least pain doing it.

Conclusion

It is my firm belief that our nation's obsession with low-fat diet and excessive protection from the sun is negatively affecting our children's health in alarming ways. Our children's bodies, in trying to cope with the resulting deficiencies in vitamin D, fats, and calcium, are forced to make tough choices among alternative outcomes that are equally bad but in different ways. They can become obese, in which case there will be enough fat for their brain to develop well, but then they will face all the consequences of metabolic syndrome: increased susceptibility to infection, increased incidence of asthma and allergies, increased risk to heart disease and type II diabetes, etc. The alternative is to stay thin, in which case there will be inadequate fat to supply the brain. Now they will be faced with syndromes like ADHD, Aspergers' and depression, because their brains are starved for fat and can't develop properly.

Those who have opted for the obesity tactic have left themselves extremely vulnerable to the upcoming swine flu epidemic. I predict that America will see a significantly higher percentage of childhood deaths from swine flu than most if not all other nations, due, in my view, to our obsession with low-fat diet and over-protection from the sun.

If we abandon these two widespread practices, our children will become much healthier. With adequate vitamin D, calcium and fat, their brains will develop well, and their bodies can stay thin. Their improved health prognosis will allow them to lead much more productive lives, and will help alleviate our current crisis in health care funding.

References:
[1] Arunabh S, Pollack S, Yeh J, Aloia JF., "Body fat content and 25-hydroxyvitamin D levels in healthy women." J Clin Endocrinol Metab. 2003 Jan;88(1):157-61.

[2] Blum, M., Dawson-Hughes, B., Dolnikowski, G., Seyoum, E., Harris, S.S. "Vitamin D3 in Fat Tissue." Endocrine Journal. 33(1):90-94, 2008.

[3] Foss Y.J.,"Vitamin D deficiency is the cause of common obesity," Med Hypotheses, Mar;72(3):314-21, 2009.

[4] A.A. Ginde, J.M. Mansbach and C. A. Camargok, "Association Between Serum 25-Hydroxyvitamin D Level and Upper Respiratory Tract Infection in the Third National Health and Nutrition Examination Survey," Arch Intern Med. 169: 384-390, 2009.

[5] Barry Groves, Trick and Treat: How 'Healthy Eating' is Making us Ill, Hammersmith Press, 2008.

[6] R.P. Heaney, "Vitamin D and Calcium Interactions: Functional Outcomes," American Journal of Clinical Nutrition, Vol. 88, No. 2, 541S-544S, August 2008.

[7] L. Jeng, A. V Yamshchikov, S.E. Judd. H.M. Blumberg, G.S. Martin, T.R. Ziegler and V.Tangpricha, "Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis," Journal of Translational Medicine, 7:28, April, 2009.

[8] E. Kamycheva, R.M. Joakimsen, and R.Jorde, "Intakes of calcium and vitamin d predict body mass index in the population of Northern Norway," J Nutr. 2003 Jan;133(1):102-6.
[9] Kumar, J. Pediatrics, Vol 124, September 2009.

[10] Lange, J.R. et al., "Melanoma in children and teenagers: An analysis of patients from the National Cancer Data Base." J. Clinical Oncology, 2007 Apr 10; 25:1363-8.

[11] U. Ravnskov, M.D., PhD, Fat and Cholesterol are Good For You,, G. B. Publishing, Sweden, 2009.

[12] Sun, X., Zeme, M.B., "Dietary Calcium regulates Ros prudiction in aP2-agouti transgenic mice on high-fat/high-sucrose diets," Int J. Obes (Lond) 30:1341-1346, 2006.

[13] X. Sun, K. L. Morris and M. B. Zemel. "Role of Calcitriol and Cortisol on Human Adipocyte Proliferation and Oxidative and Inflammatory Stress: A Microarray Study," Nutrigenet Nutrigenomics;1:30-48, 2008

[14] Gary Taubes, Good Calories Bad Calories:Challenging the Conventional Wisdom on Diet, Weight Control, and Disease., Alfred A. Knopf., 2007.

[15] R.L Wolf, J.A Cauley, C.E Baker, R.E. Ferrell, M. Charron, A.W. Caggiula, L.M. Salamone, R.P. Heaney and L.H. Kuller, "Factors associated with calcium absorption efficiency in pre- and perimenopausal women," American Journal of Clinical Nutrition, Vol. 72, No. 2, 466-471, August 2000.

[16] Zemel, M.B., "Calcium and Dairy Modulation of Obesity Risk," Obes. Res. 13:192-193, 2005.

[17] Zemel MB, Miller SL., "Dietary calcium and dairy modulation of adiposity and obesity risk," Nutr Rev. Apr;62(4):125-31, 2004.

[18] Zemel, MB, Richards, J., Milstead, A., Campbell, P, "Effects of Calcium and Dairy on Body Composition and Weight Loss in African-American Adults," Obesity Research 13:1218-1225, 2005.

[19] M.B. Zemel, H. Shi, B. Greer, D. Dirienzo and P. C. Zemel, "Regulation of adiposity by dietary calcium" The FASEB Journal 14:1132-1138, 2000.