Romanesco Broccoli in a Beaker

One of the most consistent themes of nutrition science is that vitamin supplements (pills, powders, liquids, etc.) are almost never able to mimic the beneficial effects of foods that contain the same vitamins. Now new evidence suggests that high doses of these antioxidant supplements–but not whole foods containing them–may actually block the beneficial effects of exercise on insulin sensitivity and metabolism.

Exercise has countless benefits for people of all levels of fitness. One of the most important of these is its ability to improve insulin sensitivity and increase metabolism. For this reason, exercise is considered among the most effective ways to protect against type 2 diabetes.

One of the byproducts of exercise, however, is the production of free radicals that results from the breakdown of oxygen in the muscles. These reactive oxygen molecules can damage cells and DNA, and are implicated in many chronic diseases. Since antioxidants can easily neutralize these reactive oxygen molecules, it has been assumed that antioxidants such as vitamins C and E could only benefit the body.

A new study published in the Proceedings of the National Academy of Sciences suggests that rather than help protect against oxidative damage from exercise, high doses of antioxidant supplements may actually hinder the body’s natural protection against oxidative damage and block exercise-induced metabolic benefits.

In the study, human subjects were given either placebo or 500 mg vitamin C twice per day and 400 IU vitamin E. They were then trained in both cardio and strength training workouts at the gym for 5 consecutive weekdays, 4 weeks in a row. This trial was performed on both previously trained and untrained individuals.

Metabolic rates were tested by blood sample both before the trial and after 1 and 4 weeks of training. Muscle biopsies were taken both before and after the trial for all participants. Several measures of metabolism and insulin sensitivity were measured including plasma glucose concentrations, plasma insulin concentrations, maximal oxygen uptake (VO₂ max), as well as several molecular markers in muscle that are linked to insulin sensitivity and are known to promote the body’s natural defense against oxidative damage.

The researchers found that exercise improved measures of insulin sensitivity in all individuals except those given antioxidant supplements. Also, molecules that protect against oxidative damage are upregulated in response to training, but not when antioxidants are administered.

Previous studies suggest that the body’s natural defenses against oxidative damage require activation by a small amount of reactive oxygen chemicals in the body. These same chemicals have been shown to mediate insulin sensitivity in muscles, and in this study both were shown to be blocked by high antioxidant administration.

The researchers suggest that small doses of reactive oxygen molecules such as the amounts produced by exercise are necessary to induce the body’s natural defense against oxidative damage, and that this process is essential for mediating exercise-induced insulin sensitivity. If this is true it could mean that some (but not all) of the metabolic benefits of exercise could be limited by taking high doses of vitamin supplements. This may be particularly important to individuals at high risk for type 2 diabetes.

Interestingly, foods that contain high levels of these antioxidants have previously been shown to be protective against type 2 diabetes. Although the reason for this is still unknown, the authors suggest the benefit is unlikely due to the antioxidant content of the foods and may depend on other factors.

Even if we do not understand the reason vegetables and fruits are the best source of nutrition, we can still enjoy all their benefits. If you choose to continue taking vitamin supplements, it is advisable to stick to a basic multivitamin that does not contain megadoses of one particular nutrient.

Do you take vitamin supplements? Why? How much do you take?

Tags: antioxidants, insulin, insulin sensitivity, metabolism, PNAS, Synapse, type 2 diabetes, vitamin C, vitamin E, workout

Vegetables

Most scientists agree that diet plays an important role in heart disease, but until now there has been no comprehensive analysis of which dietary factors most strongly affect disease outcome. A new meta-analysis published in the Archives of Internal Medicine reviews six decades of research (1950-2007) to assess how different dietary factors affect heart disease. Vegetables, nuts, “Mediterranean” and high-quality dietary patterns are strongly protective, while trans-fat, foods with high glycemic index or load and a “Western” dietary pattern were shown to be harmful.

The Study

This new study is unique for several reasons. First, the authors were only interested in factors that influenced heart disease directly, not simply heart disease risk factors such as cholesterol levels. Also, emphasis was placed on high-quality studies designed to identify strong dietary associations (cohort studies and randomized controlled trials) with long periods of follow up (at least one year). They asked whether the studies they reviewed were consistent with other data such as epidemiological reports, and sought to establish a causal link between diet and heart disease outcomes. Another important goal of the analysis was to identify factors that lack sufficient evidence to be conclusive and require further research.

Results

In addition to identifying vegetables, nuts, high-quality and Mediterranean dietary patterns as being strongly protective against heart disease, they also found monounsaturated fats (e.g. olive oil), dietary folate (e.g. whole grains, not supplements), dietary vitamins C and E (not supplements), alcohol consumption (in any form) and omega-3 fatty acids from fish (not plants, e.g. flax) to be moderately protective.

Factors that were not associated with heart disease in this study were dietary supplements (e.g. vitamins C and E), total fat, saturated fats, polyunsaturated fats (from plants), meat, eggs and milk. It is important to note, however, that negative findings in this analysis are not necessarily indicative of a lack of causality. Rather, it may indicate insufficient data to observe a significant positive association.

Dietary Patterns

The authors point out that “only overall healthy dietary patterns are significantly associated with coronary heart disease” in the controlled trials, while “evidence for most individual nutrients or foods is too modest to be conclusive.” They suggest that the reason an association exists for dietary patterns and not individual nutrients is that patterns “have the advantage of taking into account the complex interactions and cumulative effects of multiple nutrients within the entire diet.” The authors recommend future trials test various dietary patterns for disease outcome, including cardiovascular disease and cancer.

Taking this further, most dietary factors that were shown to be protective when consumed as part of a healthy diet were not protective when taken in supplement form. This finding bolsters the argument that overall diet rather than individual foods or nutrients are the best strategy for protecting against heart disease. The authors conclude that their findings suggest “investigating dietary patterns in cohort studies and randomized controlled trials for common and complex chronic diseases such as coronary heart disease.”

Based on their analysis, the dietary pattern that best protects against heart disease is rich in vegetables, nuts, fish, healthy fats, whole grains, and fruit. Likewise, the worst dietary pattern consists of refined carbohydrates and artificial trans-fats. The lesson: the best diet consists of plants, fish and whole foods, while processed foods contribute to heart disease.

What about red meat and saturated fats?

Interestingly, there was insufficient data to conclude that red meat or saturated fats are harmful for the heart. This is not terribly surprising, since the data has always been inconsistent. However, I would point out that many studies have looked at the role of red meat and saturated fat in coronary risk and the outcome always shows either harm or no result. And as explained above, no result can be indicative of a lack of statistical power rather than lack of causation. Importantly however, I cannot recall a single study suggesting that red meat and saturated fat is actually good for you.

From this the best we can conclude is that red meat or saturated fat may be involved in promoting heart disease, but if they are the effect is likely to be less harmful than a diet of processed foods. Practically this means small doses of saturated fat may not do much harm when eaten as a part of an overall healthy diet. This is a fairly compelling argument for exercising moderation.

Conclusions

Before you run out and order a ribeye, keep in mind that heart disease is not the only debilitating chronic disease that plagues our culture. Red meat is also associated with several kinds of cancer. Likewise, refined carbohydrates are highly correlated with type 2 diabetes. Vegetables and whole grains are protective against these other diseases as well, and fish may play a role in protecting against neurodegenerative diseases.

The take home lesson is that both diet and disease are complex systems that involve innumerable factors in several different regions of the body. When choosing what to eat it is important that you consider the context of your overall diet and do not get caught up is single foods or a single disease threat.

Tags: dietary pattern, fish, heart disease, Mediterranean diet, nuts, omega-3, red meat, refined carbs, saturated fat, trans fat, vegetables, whole grains

Drug treatments that raise the “good” high density lipoprotein (HDL) cholesterol do not improve health outcomes, according to a new analysis. But some researchers suspect raising HDL through lifestyle changes may still be effective in treating heart disease.

HDL is the form of cholesterol that actively removes dangerous lipids from the blood, and has long been thought to be protective against heart disease. This form of cholesterol is believed to work in opposition to low density lipoprotein (LDL) cholesterol, which is strongly correlated with heart disease and cardiovascular mortality. Thus the ratio of HDL to LDL cholesterols is often considered the most important indicator of heart disease risk.

Strong clinical evidence shows that LDL lowering drugs like statins can protect against heart disease and cardiovascular mortality. However there is still no effective way of improving cardiovascular outcomes by directly targeting HDL cholesterol.

Pharmacological treatments that raise HDL cholesterol levels include fibrates, niacin and a Pfizer drug called Torcetrapib. However, trials that tested these drugs for improved cardiovascular outcome have yielded mixed results. Rather than lowering mortality risk, evidence suggests that fibrates and Torcetrapib actually increase mortality in patients. Some trials have shown niacin to be effective at reducing cardiovascular events, but the data are inconsistent.

A new meta-analysis published in the British Medical Journal asked whether pharmacological treatments that are known to raise HDL can improve cardiovascular outcomes. After adjusting for several known confounders (including the effect of LDL cholesterol) pharmacological treatments that raise HDL were not effective at protecting against heart disease.

Does this mean that HDL is not important for heart disease? Not necessarily.

The original studies that implicated HDL in heart protection were observational. For example, it was shown in the Framington Heart Study that people with HDL levels greater than 60 mg/dL have a reduced risk of heart disease compared to individuals with lower HDL. Likewise, individuals with less than 40 mg/dL of blood HDL are considered at risk for coronary heart disease, even when LDL cholesterol is relatively low.

Additionally, lifestyle choices that contribute to raising HDL are associated with a lower risk of heart disease. Examples of these are physical activity, weight loss, not smoking, increased omega-3 fatty acid consumption, decreased trans fat consumption, alcohol consumption and dietary soluble fiber. Also, diets low in saturated fat but relatively high in unsaturated fats have been shown to raise HDL and decrease heart disease risk.

All these HDL raising activities can improve cardiovascular outcome. However, this does not mean that HDL itself prevents heart disease. Rather, it seems to be a good biomarker (observational correlate) of heart disease.

Why are pharmacological methods of raising HDL not helpful (and possibly even harmful) at treating heart disease?

One possible explanation for this discrepancy is the observation that HDL has different forms, some that are protective and others that are harmful. For instance, some interventions may raise HDL cholesterol by limiting its breakdown (harmful), while others raise it by increasing HDL production (more beneficial). Also, some methods that increase HDL do so in a way that creates new problems, such as increased blood pressure.

The complex interaction between pharmacological interventions, HDL metabolism and cardiovascular outcome may have made it difficult to detect any benefit of raising HDL cholesterol in this meta-analysis. Since pharmacological intervention for raising HDL does not consistently help (and sometimes harms) cardiovascular outcome, lifestyle changes remain the most promising target for raising HDL to protect against heart disease.

Anyone want to guess how high my HDL cholesterol is??

Tags: British Medical Journal, cholesterol, Framington Heart Study, HDL, heart disease, LDL, omega-3, statins

The Centers for Disease Control and Prevention (CDC) just released their 2005 report on cancer statistics. The web-based report contains official federal government statistics for cancer incidence in 96% of the United States population and mortality statistics for 100%. This is the seventh time the CDC’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology and End Results Program have combined registries to offer official federal statistics on cancer incidence and mortality for a single year.

Rates of cancer incidence are reported as the number of newly reported cases per 100,000 people. In 2005, the top four most common cancer diagnoses have not changed since 2000 and represent diseases strongly associated with lifestyle factors.

The number one diagnosed cancer in the US is prostate cancer (142.4), followed by breast (117.7), lung (67.7) and colorectal (48.3) cancers. The deadliest cancer is of the lung (52.8), while the mortality rates from prostate (24.7) and breast (24.0) cancer are nearly identical. Colorectal cancer is the fourth deadliest cancer (17.4).

Cancer is the second leading cause of death in the US, with heart disease being the first. Though most of us associate heart disease with lifestyle factors, cancer is usually regarded more fatalistically as being random or due primarily to genetics. While genetics does play a factor in some cancer cases, vast amounts of epidemiological data indicate that lifestyle factors, particularly diet and smoking, can largely account for high cancer rates in affluent countries such as the US.

There is abundant evidence that diets high in animal products and refined carbohydrates, and low in vegetables contribute to cancers of the prostate, breast and colon. A similar dietary pattern is responsible for cardiovascular disease, diabetes and neurodegenerative diseases. What is striking about cancer, however, is that there are no known drugs that stymie its development. Statins do not protect against cancer, nor do multivitamins.

The best diet to prevent all these diseases of affluence is a plant-based, whole foods diet.

Does fear of cancer impact your eating habits?

Tags: cancer, CDC, Centers for Disease Control, statistics

Vitamin D

Both environmental and genetic factors seem to play a role in the development of multiple sclerosis (MS), but determining an exact cause of the disease has been elusive. Now new evidence suggests that vitamin D may play a direct role in regulating a gene known to be associated with MS. This finding helps bridge the gap between environmental and genetic risk factors, and strengthens the hypothesis that vitamin D could be instrumental in MS prevention.

MS is an autoimmune disease that attacks myelin, a component of the nervous system essential for the conduction of neural impulses. Onset of MS usually occurs between the ages 18 and 35, and is more prevalent in females than males.

One of the most interesting epidemiological findings associated with MS is that it is more common in regions farthest from the equator, with a few notable exceptions. Climate, sunlight and vitamin D are all suspected candidates in the occurrence of MS, as are genetics and diet. Importantly, the relationship between geographical location and MS risk seems to be most significant in early childhood years. After age 15, risk of MS for immigrants is closer to that of their home country than to that of their new country.

Sunshine is the most common source of vitamin D for humans. Vitamin D is created when ultraviolet B (UVB) light contacts skin. Dietary vitamin D is rare, though it can be obtained at significant levels with certain foods, particularly oily fish (e.g. sardines and salmon). Notably, Norway and many Asian countries have relatively low prevalence of MS. It has been suggested that fish consumption is the reason for these regional discrepancies that cannot be explained by sun exposure. This makes vitamin D a particularly strong candidate for MS prevention.

In addition to environmental factors, certain genetic risks are linked to MS. In particular, proteins associated with the body’s immune cells are mutated in many MS cases. Mutations in these proteins disrupt the ability of immune cells to determine which particles in the body are foreign and which are “self.” When this happens, the cells get confused and begin to attack their own body’s tissues.

A new article published last week in PLoS Genetics investigated the relationship between vitamin D and the genetic variants associated with MS. They found that vitamin D directly interacts with these genes at a molecular level, providing insight into the mechanism by which vitamin D may affect the disease. Though it is still not clear what specific role vitamin D plays in its interaction with MS genes, a new avenue of exploration has opened up into MS etiology.

The tie between vitamin D and MS is still vague, but it is a good idea to ensure your vitamin D levels are adequate. People living at latitudes greater than 40 degrees from the equator (San Francisco is on the border) should be taking vitamin D supplements. This is true for many reasons; MS is not the only disease that is linked to low vitamin D levels.

Vitamin D pills are now easy to find, and can be obtained at both Trader Joe’s and Whole Foods. Take one or two oil-based 1000IU vitamin D supplements daily. Men should avoid vitamin D supplements that contain calcium, because excess calcium increases risk of prostate cancer.

Do you take vitamin D supplements?

UPDATE: This article can also be found in Synapse.

Tags: multiple sclerosis, San Francisco, sun, sun tan, tanning, vitamin D, vitamins